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1.  Periodontal Disease and the Oral Microbiota in New-Onset Rheumatoid Arthritis 
Arthritis and rheumatism  2012;64(10):3083-3094.
Objective
To profile the subgingival oral microbiota abundance and diversity in never-treated, new-onset rheumatoid arthritis (NORA) patients.
Methods
Periodontal disease (PD) status, clinical activity and sociodemographic factors were determined in patients with NORA, chronic RA (CRA) and healthy subjects. Massively parallel pyrosequencing was used to compare the composition of subgingival microbiota and establish correlations between presence/abundance of bacteria and disease phenotypes. Anti-P. gingivalis antibodies were tested to assess prior exposure.
Results
The more advanced forms of periodontitis are already present at disease onset in NORA patients. The subgingival microbiota of NORA is distinct from controls. In most cases, however, these differences can be attributed to PD severity and are not inherent to RA. The presence and abundance of P. gingivalis is directly associated with PD severity as well, is not unique to RA, and does not correlate with anti-citrullinated peptide antibody (ACPA) titers. Overall exposure to P. gingivalis is similar in RA and controls, observed in 78.4% and 83.3%, respectively. Anaeroglobus geminatus correlated with ACPA/RF presence. Prevotella and Leptotrichia species are the only characteristic taxa in the NORA group irrespective of PD status.
Conclusions
NORA patients exhibit a high prevalence of PD at disease onset, despite their young age and paucity of smoking history. The subgingival microbiota of NORA patients is similar to CRA and healthy subjects of comparable PD severity. Although colonization with P. gingivalis correlates with PD severity, overall exposure is similar among groups. The role of A. geminatus and Prevotella/Leptotrichia species in this process merits further study.
doi:10.1002/art.34539
PMCID: PMC3428472  PMID: 22576262
4.  Colchicine Use Is Associated with Decreased Prevalence of Myocardial Infarction in Patients with Gout 
The Journal of rheumatology  2012;39(7):1458-1464.
Objective
The ability of antiinflammatory strategies to alter cardiovascular risk has not been rigorously examined. Colchicine is an antiinflammatory agent that affects macrophages, neutrophils, and endothelial cells, all of which are implicated in the pathogenesis of cardiovascular disease. We examined whether colchicine use was associated with a reduced risk of myocardial infarction (MI) in patients with gout.
Methods
We conducted a retrospective, cross-sectional study of all patients with an International Classification of Diseases, 9th ed, code for gout in the electronic medical record (EMR) of the New York Harbor Healthcare System Veterans Affairs network and ≥ 1 hospital visit between August 2007 and August 2008. Hospital pharmacy data were used to identify patients who had filled at least 1 colchicine prescription versus those who had not. Demographics and CV comorbidities were collected by EMR review. The primary outcome was diagnosis of MI. Secondary outcomes included all-cause mortality and C-reactive protein (CRP) level.
Results
In total, 1288 gout patients were identified. Colchicine (n = 576) and no colchicine (n = 712) groups had similar baseline demographics and serum urate levels. Prevalence of MI was 1.2% in the colchicine versus 2.6% in the no-colchicine group (p = 0.03). Colchicine users also had fewer deaths and lower CRP levels, although these did not achieve statistical significance. Colchicine effects persisted when allopurinol users were excluded from the analysis.
Conclusion
In this hypothesis-generating study, gout patients who took colchicine had a significantly lower prevalence of MI and exhibited trends toward reduced all-cause mortality and lower CRP level versus those who did not take colchicine.
doi:10.3899/jrheum.111533
PMCID: PMC3733459  PMID: 22660810
GOUT; COLCHICINE; MYOCARDIAL INFARCTION; MORTALITY; C-REACTIVE PROTEIN
5.  Reproducibility of Musculoskeletal Ultrasound for Determining Monosodium Urate Deposition: Concordance Between Readers 
Arthritis care & research  2011;63(10):1456-1462.
Objectives
Criteria for sonographic diagnosis of monosodium urate (MSU) crystal deposition have been developed, but the inter-reader reproducibility of this modality is not well-established. We therefore assessed agreement using a systematic approach.
Methods
50 male subjects ages 55-85 were recruited during primary care visits to an urban VA hospital, and were assessed by musculoskeletal ultrasound (MSK-US) of the knees and 1st metatarsophalangeal (MTP) joints to evaluate for the “double contour” sign and tophi as evidence of MSU crystal deposition. Images were read by two blinded rheumatologists trained in MSK-US, and degree of concordance was determined for individual patients, total joints, femoral articular cartilage (FAC) and 1st MTP joints. Patients were further categorized into three diagnostic groups: gout, asymptomatic hyperuricemia (AH) (no gout, serum uric acid (UA) ≥ 6.9 mg/dL) and controls (no gout, UA ≤ 6.8 mg/dL), and reader concordance within these three groups was assessed.
Results
We observed almost perfect agreement between readers for: 1) individual patients (yes/no) (n=50, 100% agreement, kappa=1.000); 2) total joints (n=200, 99% agreement, kappa=0.942); 3) FAC (n=100, 99% agreement, kappa=0.942); and 4) 1st MTPs (n=100, 99% agreement, kappa=0.942). Furthermore, findings by side (right/left) and diagnostic group (gout, AH, control) showed substantial to almost perfect concordance for all measures. MSU deposition was seen most commonly in gout patients, and deposition was also seen in some patients with asymptomatic hyperuricemia, but in only one control.
Conclusion
MSK-US is reliable for detecting MSU deposition in FAC and 1st MTPs in gout and AH.
doi:10.1002/acr.20527
PMCID: PMC3183112  PMID: 21702086
6.  Advances in the management of gout: Critical appraisal of febuxostat in the control of hyperuricemia 
Gout recently passed rheumatoid arthritis to become the most common inflammatory arthritis in the United States (US). However, epidemiologic studies indicate that the quality of gout management is suboptimal owing to both patient and physician issues. Only three options for urate-lowering therapy are currently available in the US: allopurinol, probenecid, and recently, febuxostat. Probenecid is generally safe except for the occurrence of urolithiasis, but is only effective for the subset of patients with better kidney function. Allopurinol use is limited due to its side effects, potential toxicity of uncertain magnitude in patients with renal disease, and failure to achieve targeted serum urate levels. In part this failure may be due to the necessity for it to be titrated for optimal therapeutic effect. Febuxostat is a new medication that may offer several advantages and can be given as an alternative to allopurinol. We review the basic biology and clinical performance of febuxostat, and consider the potential utility of this agent in comparison to the older, better-established gout therapeutics.
PMCID: PMC3108781  PMID: 21694922
allopurinol; gout suppressants; nephrolithiasis; uric acid; urolithiasis
7.  Effect of cyclooxygenase inhibition on cholesterol efflux proteins and atheromatous foam cell transformation in THP-1 human macrophages: a possible mechanism for increased cardiovascular risk 
Both selective cyclooxygenase (COX)-2 inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) have been beneficial pharmacological agents for many patients suffering from arthritis pain and inflammation. However, selective COX-2 inhibitors and traditional NSAIDs are both associated with heightened risk of myocardial infarction. Possible pro-atherogenic mechanisms of these inhibitors have been suggested, including an imbalance in prostanoid production leaving the pro-aggregatory prostaglandins unopposed, but the precise mechanisms involved have not been elucidated. We explored the possibility that downregulation of proteins involved in reverse cholesterol transport away from atheromatous plaques contributes to increased atherogenesis associated with COX inhibition. The reverse cholesterol transport proteins cholesterol 27-hydroxylase and ATP-binding cassette transporter A1 (ABCA1) export cholesterol from macrophages. When mechanisms to process lipid load are inadequate, uncontrolled cholesterol deposition in macrophages transforms them into foam cells, a key element of atheromatous plaques. We showed that in cultured THP-1 human monocytes/macrophages, inhibition of COX-1, COX-2, or both reduced expression of 27-hydroxylase and ABCA1 message (real-time reverse transcription-polymerase chain reaction) and protein (immunoblot). The selective COX-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS398) significantly reduced 27-hydroxylase and ABCA1 message (to 62.4% ± 2.2% and 71.1% ± 3.9% of control, respectively). Incubation with prostaglandin (PG) E2 or PGD2 reversed reductions in both of these cholesterol transport proteins induced by NS398. Cholesterol-loaded THP-1 macrophages showed significantly increased foam cell transformation in the presence of NS398 versus control (42.7% ± 6.6% versus 20.1% ± 3.4%, p = 0.04) as determined by oil red O staining. Pharmacological inhibition of COX in monocytes is involved in downregulation of two proteins that mediate cholesterol efflux: cholesterol 27-hydroxylase and ABCA1. Because these proteins are anti-atherogenic, their downregulation may contribute to increased incidence of cardiac events in patients treated with COX inhibitors. Reversal of inhibitory effects on 27-hydroxylase and ABCA1 expression by PGD2 and PGE2 suggests involvement of their respective signaling pathways. NS398-treated THP-1 macrophages show greater vulnerability to form foam cells. Increased cardiovascular risk with COX inhibition may be ascribed at least in part to altered cholesterol metabolism.
doi:10.1186/ar2109
PMCID: PMC1860062  PMID: 17244362

Results 1-7 (7)