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ID PMID Title PublicationDate abstract
20191479 Functional impairment of the arterial wall in primary Sjögren's syndrome: combined action 2010 May OBJECTIVE: Primary Sjögren's syndrome (SS) shares clinical and serologic features with rheumatoid arthritis and systemic lupus erythematosus, 2 diseases characterized by acceleration of atherosclerosis. Signs of precocious atherosclerosis have also been shown in SS, although the pathogenic basis of early arterial damage is unclear. The arterial wall was functionally evaluated in SS subjects with analysis of the role played by disease-related factors. METHODS: Endothelium-dependent flow-mediated vasodilation (FMV) and endothelium-independent nitrate-mediated vasodilation (NMV) were evaluated in 45 women with SS and 59 age-matched female controls. In addition, serum soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 (VCAM-1), and nitrotyrosine were detected. RESULTS: Although patient FMV values did not differ from those of control subjects (mean +/- SD 7.4 +/- 3.6 versus 7.7 +/- 1.9; not significant), NMV was lower in SS patients than in controls (mean +/- SD 8.1 +/- 3.5 versus 10.3 +/- 2.1; P
19168158 Metabolic syndrome in rheumatological diseases. 2009 Mar Metabolic syndrome is characterized by a combination of various cardiovascular risk factors (age, gender, smoking, hypertension and dyslipidemia) that imply additional cardiovascular morbidity that is greater than the sum of the risks associated with each individual component. Herein, the authors review the rheumatological diseases in which metabolic syndrome has been studied: gout, osteoarthritis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and ankylosing spondylitis. The prevalence of metabolic syndrome in these disorders varies from 14% to 62.8%. The great majority of these studies demonstrated that this frequency was higher in rheumatological diseases than in the control populations, suggesting that either the presence or the treatment of those diseases seems to influence the risk of developing metabolic syndrome.
21253584 Current concepts: mouse models of Sjögren's syndrome. 2011 Sjögren's syndrome (SjS) is a complex chronic autoimmune disease of unknown etiology which primarily targets the exocrine glands, resulting in eventual loss of secretory function. The disease can present as either primary SjS or secondary SjS, the latter of which occurs concomitantly with another autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or primary biliary cirrhosis. Current advancements in therapeutic prevention and treatment for SjS are impeded by lack of understanding in the pathophysiological and clinical progression of the disease. Development of appropriate mouse models for both primary and secondary SjS is needed in order to advance knowledge of this disease. This paper details important features, advantages, and pitfalls of current animal models of SjS, including spontaneous, transgenic, knockout, immunization, and transplantation chimera mouse models, and emphasizes the need for a better model in representing the human SjS phenotype.
19380287 Proinflammatory and prothrombotic effects on human vascular endothelial cells of immune-ce 2009 Apr 16 OBJECTIVE: LIGHT (TNFSF 14) belongs to the tumor necrosis factor superfamily and is expressed by activated T cells as well as various types of antigen presenting cells. LIGHT binds to its cellular receptors TR2 and LTbetaR and has a co-stimulatory role in T cell activation. Here, we compared the relative expression of LIGHT in different immune cells and the biological activity of immune cell-derived LIGHT on endothelial cells. METHODS AND RESULTS: Surface expression of LIGHT and mRNA production by PBMC and isolated T cells (CD4+ or CD8+) significantly increased after stimulation with PMA (Phorbolester-12- Myristat-13-Acetat)+ionomycin. No LIGHT expression on PMA stimulated monocytes or monocytic-like THP-1 cells could be detected; differentiation of monocytes and THP-1 cells into macrophages, however, resulted in up-regulation of LIGHT. Supernatants of stimulated T cells contained higher concentrations of soluble LIGHT than macrophage supernatants normalized to cell numbers; release of soluble LIGHT was found to be dependent on metalloproteinase activity. Size determination of released soluble LIGHT by size exclusion chromatography revealed a molecular mass of approximately 60 kDa, suggesting a trimeric form. Released soluble LIGHT induced expression of proinflammatory antigens ICAM-1, tissue factor and IL-8 in human endothelial cells and caused apoptosis of IFN-g pretreated endothelial cells. Soluble LIGHT was detected at low levels in sera of healthy controls and was significantly enhanced in sera of patients with chronic hepatitis C and rheumatoid arthritis (24.93+/-9.41 vs. 129.53+/-49.14 and 172.13+/-77.64; p<0.0005). CONCLUSION: These findings suggest that among immune cells activated T lymphocytes are the main source of soluble LIGHT with released amounts of soluble LIGHT markedly higher compared to platelets. Immune cell-derived membrane-bound and soluble trimeric LIGHT is biologically active, inducing proinflammatory changes in endothelial cells. Enhanced plasma levels of soluble LIGHT in patients with chronic infections suggest a role of LIGHT in systemic inflammatory activation.
20697842 Long-term response with everolimus for metastatic renal cell carcinoma refractory to sunit 2011 Dec A 70-year-old man with metastatic renal cell carcinoma developed progressive liver metastases after 8 weeks of treatment with the multitargeted tyrosine kinase inhibitor (TKI) sunitinib. He then participated in the phase III placebo-controlled clinical trial of the oral mammalian target of rapamycin (mTOR) inhibitor everolimus, initially randomized to placebo (but had disease progression after 3 months) and crossed over to everolimus at time of unblinding. The patient had stable disease after 8 weeks (two cycles) of everolimus that was maintained until 28 months of therapy, at which time the patient had achieved a partial response. This case illustrates the potential for patients with metastatic renal cell carcinoma, a malignancy with historically poor prognosis, to derive long-term benefit from everolimus when used in a manner consistent with its approved indication (after TKI therapy with sunitinib or sorafenib).
19736810 Anti-inflammatory activity of superoxide dismutase obtained from Debaryomyces hansenii on 2009 May INTRODUCTION: Rheumatoid arthritis is an autoimmune inflammatory disease of unknown etiology, free radicals have been implicated in the genesis and perpetuation of damage in this pathology. OBJECTIVE: To evaluate the anti-inflammatory effect of Cu,Zn-superoxide dismutase (SOD) obtained from two different sources (bovine erythrocytes, Be-SOD, and Debaryomyces hansenii, Dh-SOD) with Type II Collagen-induced Arthritis model in rats. MATERIAL AND METHODS: Arthritis was induced by repeated injection of a porcine type II collagen-incomplete Freund adjuvant suspension on the back of Dark Augui (DA) rats. Arthritis was clinically evaluated throughout the study. Body weight was determined at three different times. Two different doses for each treatment (Be-SOD, Dh-SOD) were tested: 100 and 1,000 U/kg. At the end of the trial (day 28), histological analyses of the most inflamed ankle joint, as well as serum anti-collagen antibodies, were determined. RESULTS: Both sources of SOD decreased, although to a different extent, the incidence and severity of the disease. Arthritis score was lower in all treatments, except for the low dose of Be-SOD. Groups receiving either source of SOD showed a significant weight increase compared to the placebo group. Histological damage was similar in all groups. Only the group that received the highest dose of Dh-SOD showed a significant lower antibody titer; nevertheless, no correlation appears to derive from arthritis score and antibody titer. CONCLUSION: Our findings suggest that, although unable to counteract the arthritis syndrome, SOD may still be beneficial due to its anti-inflammatory activity. In the case of Dh-SOD, the best effect was observed at the highest dose tested.
19454607 The 30-kDa band from Salmonella typhimurium: IgM, IgA and IgG antibody response in patient 2009 Jul OBJECTIVE: To determine the association of Salmonella typhimurium antigens with AS by analysing the IgA, IgG and IgM antibody response to the crude lysate and the 30-kDa band from this micro-organism. METHODS: Sera from 28 AS patients, 28 HLA-B27+ healthy relatives, 28 unrelated healthy subjects and 14 RA patients were included. Salmonella typhimurium proteins were electrophoretically separated and blotted onto nitrocellulose sheets for immunodetection with sera from AS patients and unrelated healthy subjects. The electroeluted 30-kDa band (p30) and a crude lysat (StCL) from S. typhimurium were used as antigen to evaluate the IgM, IgA and IgG (total and subclasses) antibody levels by ELISA. An inhibition assay was carried out to confirm the specificity of IgG response to the p30. RESULTS: Twenty out of 28 AS patients (71.4%) and 4 out of 28 unrelated healthy subjects (14.3%) recognized a 30-kDa band from S. typhimurium with IgG antibodies. Six out of 28 AS patients (21.4%) and 4 out of 28 unrelated healthy subjects (14.3%) detected it with IgA antibodies. Recognition of p30 and StCL by both IgA and IgG antibodies was higher in AS patients than in control groups (P = 0.003, <0.001 and 0.003 for IgA and <0.001, 0.003 and 0.006 for IgG). Sera from AS patients have higher percentage of IgG antibodies p30 and IgG3 subclass was higher in AS patients than in control groups. No differences in the IgM response were found. CONCLUSIONS: Data presented suggest the association between the p30 and AS.
20339032 Protein kinase C-theta mediates negative feedback on regulatory T cell function. 2010 Apr 16 T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Protein kinase C-theta (PKC-theta) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-theta was sequestered away from the Treg immunological synapse. Furthermore, PKC-theta blockade enhanced Treg function, demonstrating PKC-theta inhibits Treg-mediated suppression. Inhibition of PKC-theta protected Treg from inactivation by TNF-alpha, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-theta-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases.
20378384 Is there a link between inflammation and abnormal lipoprotein profile in Sjögren's syndro 2010 May OBJECTIVES: To investigate the lipoprotein profile of patients with primary Sjögren's syndrome (pSS) and its association with laboratory tests, including markers of inflammation. METHODS: This is a cross-sectional study among patients with pSS and healthy controls. We analyzed the lipoprotein profile of 73 pSS patients compared to 65 healthy individuals in the control group. We further evaluated possible associations between dyslipidemia in pSS patients and laboratory parameters including: hypergammaglobulinemia, autoantibodies [antinuclear antibodies (ANA), rheumatoid factor (RF), anti-Ro, anti-La], and acute-phase reactants [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)]. RESULTS: Patients and controls were comparable regarding the demographic variables. Lipoprotein profile was similar between pSS patients and controls: total cholesterol (204.0+/-43.39 versus 206.5+/-42.76 mg/mL, P=0.73), LDL fraction (131.6+/-37.38 versus 130.62+/-38.24 mg/dL, P=0.88) and HDL fraction (49.7+/-13.5 versus 51+/-11.5mg/dL, P=0.56), triglycerides (129.3+/-81.0 versus 116.8+/-53.5mg/dL, P=0.29). However, patients with pSS had a strong trend to present dyslipidemia when compared to healthy individuals (76.7% versus 61.5%, P=0.06). The presence of dyslipidemia in pSS was associated with increased ESR (44.05+/-28.07 versus 28.28+/-18.00, P=0.03), but not with other laboratory markers of the disease and inflammation. DISCUSSION/CONCLUSION: pSS patients frequently present abnormal lipid profile, which are associated with higher levels of ESR. Thus, similar to other systemic inflammatory diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), lipid profile should be evaluated in pSS patients, with the aim of initiating specific therapeutic strategy for prevention of cardiovascular events.
19266104 Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches 2009 BACKGROUND: Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2) is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. METHODOLOGY/PRINCIPAL FINDINGS: We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. CONCLUSIONS/SIGNIFICANCE: Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases.
20132813 KR-003048, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. 2010 Apr 25 The tumor necrosis factor-alpha (TNF-alpha) cytokine, secreted by activated monocytes/macrophages and T lymphocytes, is implicated in several diseases, including rheumatoid arthritis, chronic obstructive pulmonary disease, inflammatory bowel disease, and osteoporosis. Monocyte/macrophage production of TNF-alpha is largely driven by p38alpha mitogen-activated protein kinase (MAP kinase), an intracellular soluble serine-threonine kinase. p38alpha MAP kinase is activated by growth factors, cellular stresses, and cytokines such as TNF-alpha and interleukin-l (IL-I). The primary contribution of p38alpha activation to excess TNF-alpha in settings of both chronic and acute inflammation has instigated efforts to find inhibitors of this enzyme as possible therapies for associated disease states. Analogue design, synthesis, and structure-activity studies led to the identification of 5-tert-butyl-N-cyclopropyl-2-methoxy-3-{2-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-2-oxo-acetylamino}-benzamide (KR-003048) as a potent inhibitor of the p38 MAP kinase signaling pathway in vitro and in vivo. The inhibition in vitro of human p38alpha enzyme activity and lipopolysaccharide (LPS)-induced p38 activation and subsequent TNF-alpha release is described. KR-00348 was demonstrated to be a potent inhibitor of inflammatory cytokine production ex vivo in rat and human whole blood, and showed good oral bioavailability. Additionally, efficacy in mouse and rat models of acute and chronic inflammation was obtained. KR-003048 possessed therapeutic activity in acute models, demonstrating substantial inhibition of carrageenan-induced paw edema and in vivo LPS-induced TNF release at 30mg/kg p.o. Collagen-induced arthritis in mice was significantly inhibited by 10 and 30mg/kg doses of KR-003048. Evidence for disease-modifying activity in this model was indicated by histological evaluation of joints.
19412018 Assuring optimal physiologic craniocervical alignment and avoidance of swallowing-related 2009 May STUDY DESIGN: A retrospective review. OBJECTIVE: To assess the utility of preoperative halo immobilization in the avoidance of swallowing complications-associated occipitocervical fixation. SUMMARY OF BACKGROUND DATA: The craniocervical region is commonly affected by a number of pathologic processes. Fixation of the upper cervical spine to the occiput provides an excellent means of treating these conditions. Occipitocervical fixation, however, is associated with a number of potential complications. One under-reported postoperative complication is the swallowing difficulty that some patients experience. Another is the overall patient dissatisfaction with postoperative head position. One means that the authors have used to avoid these complications is the use of preoperative halo vest fixation. METHODS: In this article, we report our experience with preoperative halo vest immobilization for occipitocervical fusion in 12 consecutive patients over a 5-month period and its effect on postoperative complications. We also report our experience with the index case of this series in which the patient required operative revision because of severe postoperative dysphagia and stridor after an occipitocervical fusion. RESULTS: All patients achieved satisfactory postoperative head position using the preoperative halo immobilization technique. One patient experienced transient dysphagia, which did not require intervention. No patients experienced any complications related to the placement of the halo vest itself. CONCLUSIONS: Preoperative halo immobilization allows patients, who are going to have their head permanently fixed in a particular position, to determine if they are able to tolerate the new head position. This allows the surgeon to adjust the head position before permanently locking the patient in the position, if necessary. We, therefore, advocate the use of preoperative halo immobilization as a means of assuring physiologic craniocervical neutrality and the avoidance of the resultant complications.
20398804 ERK activation by GM-CSF reduces effectiveness of p38 inhibitor on inhibiting TNFalpha rel 2010 Jul Tumor necrosis factor alpha (TNFalpha), a pro-inflammatory factor, plays an important role in many inflammatory diseases. Inhibition of p38 is being pursued as a pharmaceutical treatment to reduce TNFalpha release. Since a variety of cytokines and factors may exist at different amounts in patients, we explored how differences in the cytokine environment impact p38 inhibitor potency. Cytokine co-stimulation with LPS was compared against LPS stimulation alone. In both differentiated U937 cells and peripheral monocytes, GM-CSF co-stimulation with LPS increased TNFalpha release and led to an increased residual TNFalpha levels with p38 inhibitor. Adding MEK inhibitor in the presence of p38 inhibitor further reduced TNFalpha release suggesting that the ERK pathway plays a role in GM-CSF induced reduction of the p38 inhibitor potency. When cells were stimulated with different concentrations of LPS and GM-CSF, the minimal TNFalpha level obtained by MEK inhibitor was not dependent on the stimulation condition; while it was dependent on GM-CSF level for p38 inhibitor. TNFalpha release in the presence of combinations of p38 and MEK inhibitors under different stimulation conditions was measured. A linear model was created using the initial relative ERK and p38 phosphorylation levels and p38 and MEK inhibitor concentrations to accurately predict released TNFalpha level, suggesting these four parameters are sufficient to predict TNFalpha levels. We then used the model to show that with same TNFalpha levels, higher ERK pathway activity reduces p38 inhibitor potency. These results suggest that p38 inhibitor will be a more potent anti-TNFalpha therapy for patients with low ERK pathway activity.
19755614 Phagocyte-specific S100A8/A9 protein levels during disease exacerbations and infections in 2009 Oct OBJECTIVE: S100A8 and S100A9 are calcium binding proteins of the S100 family highly expressed in neutrophils and monocytes. S100 proteins are novel ligands of TLR4 important in modulating inflammation. High levels of S100A8/A9 found in human inflammatory diseases are a marker of disease activity in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). We determined levels of S100A8/A9 in sera of patients with systemic lupus erythematosus (SLE) and analyzed their relation to clinical variables of disease activity. METHODS: A group of 93 patients with SLE were studied over a period of 3 years, and 143 serum samples were analyzed. S100A8/A9 serum concentrations were determined by a sandwich ELISA. Sera from 10 primary Sjögren's syndrome (pSS) patients and 50 healthy volunteers were used as controls. Correlations to SLEDAI, ANA, anti-dsDNA, WBC, CH50, C4, and CRP were made. In addition, infections were recorded in all SLE patients. RESULTS: Serum levels of S100A8/A9 were significantly (p = 0.04) higher in SLE patients (1412 +/- 664 ng/ml) versus healthy controls (339 +/- 35 ng/ml) and pSS patients (400 +/- 85 ng/ml). The only significant correlation (r = 0.219; p = 0.015) was found was between S100A8/A9 and SLEDAI. Further, SLE patients with concomitant infections had higher serum levels of S100A8/A9 (39300 +/- 13375 ng/ml) than those without infections (1150 +/- 422 ng/ml). CONCLUSION: Serum levels of S100A8/A9 are significantly raised in SLE versus pSS patients and healthy controls and can be correlated to a disease activity index. S100A8/A9 is a more relevant marker of infection in SLE patients.
21149752 The comparative safety of analgesics in older adults with arthritis. 2010 Dec 13 BACKGROUND: The safety of alternative analgesics is unclear. We examined the comparative safety of nonselective NSAIDs (nsNSAIDs), selective cyclooxygenase 2 inhibitors (coxibs), and opioids. METHODS: Medicare beneficiaries from Pennsylvania and New Jersey who initiated therapy with an nsNSAID, a coxib, or an opioid from January 1, 1999, through December 31, 2005, were matched on propensity scores. We studied the risk of adverse events related to analgesics using incidence rates and adjusted hazard ratios (HRs) from Cox proportional hazards regression. RESULTS: The mean age of participants was 80.0 years, and almost 85% were female. After propensity score matching, the 3 analgesic cohorts were well balanced on baseline covariates. Compared with nsNSAIDs, coxibs (HR, 1.28; 95% confidence interval [CI], 1.01-1.62) and opioids (1.77; 1.39-2.24) exhibited elevated relative risk for cardiovascular events. Gastrointestinal tract bleeding risk was reduced for coxib users (HR, 0.60; 95% CI, 0.35-1.00) but was similar for opioid users. Use of coxibs and nsNSAIDs resulted in a similar risk for fracture; however, fracture risk was elevated with opioid use (HR, 4.47; 95% CI, 3.12-6.41). Use of opioids (HR, 1.68; 95% CI, 1.37-2.07) but not coxibs was associated with an increased risk for safety events requiring hospitalization compared with use of nsNSAIDs. In addition, use of opioids (HR, 1.87; 95 CI, 1.39-2.53) but not coxibs raised the risk of all-cause mortality compared with use of nsNSAIDs. CONCLUSIONS: The comparative safety of analgesics varies depending on the safety event studied. Opioid use exhibits an increased relative risk of many safety events compared with nsNSAIDs.
19376499 Defects of mitogen-activated protein kinase in ICOS signaling pathway lead to CD4(+) and C 2009 In this study, hypoproliferation and defects of effectors and cytokines in CD4(+) and CD8(+) T-cells via ICOS costimulation were found in active SLE patients, relative to normal individuals and RA patient controls. Exogenous IL-2 can partially reverse those defects. In addition, low level of ERK phosphorylation in ICOS-mediated signaling pathway was discovered in lupus CD4(+) and CD8(+) T-cells. When blocked with ERK-specific chemical inhibitor PD98059, cell proliferation and IL-2 production via ICOS costimulation from both CD4(+) and CD8(+) T-cells will be severely inhibited. These findings confirmed the dysfunction of both CD4(+) and CD8(+) T-cells after ICOS costimulation in lupus patients and most importantly pointed out that impairment of ERK activation might be one of the critical factors involved in ICOS-mediated IL-2 and T-cell hypoproliferation in active SLE.
19564572 The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote 2009 Sep The nuclear protein HMGB1 has previously been demonstrated to act as an alarmin and to promote inflammation upon extracellular release, yet its mode of action is still not well defined. Access to highly purified HMGB1 preparations from prokaryotic and eukaryotic sources enabled studies of activation of human PBMC or synovial fibroblast cultures in response to HMGB1 alone or after binding to cofactors. HMGB1 on its own could not induce detectable IL-6 production. However, strong enhancing effects on induction of proinflammatory cytokine production occurred when the protein associated with each of the separate proinflammatory molecules, rhIL-1beta, the TLR4 ligand LPS, the TLR9 ligand CpG-ODN, or the TLR1-TLR2 ligand Pam3CSK4. The bioactivities were recorded in cocultures with preformed HMGB1 complexes but not after sequential or simultaneous addition of HMGB1 and the individual ligands. Individual A-box and B-box domains of HMGB1 had the ability to bind LPS and enhance IL-6 production. Heat denaturation of HMGB1 eliminated this enhancement. Cocultures with HMGB1 and other proinflammatory molecules such as TNF, RANKL, or IL-18 did not induce enhancement. HMGB1 thus acts broadly with many but not all immunostimulatory molecules to amplify their activity in a synergistic manner.
19139669 O-C2 angle as a predictor of dyspnea and/or dysphagia after occipitocervical fusion. 2009 Jan 15 STUDY DESIGN: A retrospective clinical study. OBJECTIVE: To confirm the impact of the O-C2 angle on dyspnea and dysphagia after posterior occipitocervical (O-C) fusion. SUMMARY OF BACKGROUND DATA: Dyspnea and dysphagia are complications of posterior O-C fusion with malalignment, and may be prolonged or occasionally serious. However, it is difficult to select a safe alignment during surgery, and no indicators of the appropriate alignment have been available to preclude these complications. METHODS: The authors retrospectively reviewed 29 consecutive patients who had undergone O-C or occipitocervicothoracic fusion between 2003 and 2008. Data were analyzed for O-C2 angles on plain radiographs and the axial computed tomographic cross-sectional areas of the oropharynx just cranial to the epiglottis before and after surgery. The patients were grouped according to whether they developed postoperative dyspnea and/or dysphagia (group A) or not (group B). RESULTS: After surgery, 4 patients complained of dysphagia, and 1 patient had dyspnea and dysphagia, although they had all undergone short O-C fusions. The difference in the O-C2 angle (dOC2A = postoperative O-C2 angle--preoperative O-C2 angle) and the percentage change in the cross-sectional area of the oropharynx (S) before and after surgery (% dS) were linearly correlated. Both dOC2A and % dS were significantly lower in group A than in group B. All patients with dOC2A of less than -10 degrees showed % dS of less than -40%, and developed dyspnea and/or dysphagia after surgery. Conversely, no patients with positive dOC2A developed these complications. CONCLUSION: The O-C2 angle has considerable impact on dyspnea and/or dysphagia after O-C fusion. The O-C2 angle is easily measured during surgery and can be a practical index with which to avoid postoperative dyspnea and dysphagia.
21054636 The current state of care in gout: Addressing the need for better understanding of an anci 2010 Nov PURPOSE: To enable clinicians to initiate appropriate steps for long-term management of gout, including controlling acute exacerbations and pain and sustaining target serum uric acid (SUA) levels to control hyperuricemia as the underlying metabolic disorder. DATA SOURCES: Incorporation of pertinent rheumatology and primary care literature seeking a comprehensive overview about the disease state of gout and its symptoms, comorbidities, and impact on quality of life, with a key focus on the role of serum uric acid, evidence-based approaches to long-term management of gout, and the importance of a functioning clinician-patient relationship. CONCLUSIONS: Gout is increasingly recognized as a prevalent chronic disease state requiring appropriate long-term management while controlling for risk factors and comorbid conditions. Effective treatment options can help gout patients achieve therapeutic SUA targets to control gout flares and prevent potentially destructive disease manifestations. Patient education is an important element in achieving treatment goals and ensuring adherence. IMPLICATIONS FOR PRACTICE: Effective treatment plans for any gout patient must be guided by a long-term approach that focuses on sustained control of hyperuricemia, while providing continuous control of chronic disease. Patient education can be a key element in this process.
19741716 Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases. 2010 Mar Copy number variation (CNV) in the human genome is an important determinant of susceptibility to autoimmune diseases. Many autoimmune diseases share similar clinical and pathogenic features. Thus, CNVs of genes involved in immunity may serve as shared determinants of multiple autoimmune diseases. Here, we determined the association between CNV in the gene encoding FCGR3B with the risk of developing autoimmune diseases and whether the observed associations are modified by the CNV in CCL3L1 (CC chemokine ligand 3-like 1), a gene encoding a potent chemokine. In a cross-sectional study of 774 subjects, we estimated FCGR3B and CCL3L1 gene copy number in 146, 158 and 61 subjects with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS), respectively, and 409 healthy controls. The median gene dose of FCGR3B in the study population was two. FCGR3B copy number < or >2 was associated with an increased risk of SLE and primary SS but not RA. This association was mostly evident in subjects who also had two copies of CCL3L1. Thus, our data suggest that epistatic interactions between CNV of FCGR3B and CCL3L1, two immune response genes, may influence phenotypically related autoimmune diseases.