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ObjectiveTo describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up.MethodsThe systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used.Results31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors.ConclusionsIn some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis.

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

ObjectiveAnti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study.MethodsInformation and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA.ResultsPrevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p

The authors offer some comments on the advantages and possible drawbacks of using the SLICC criteria in longitudinal observational studies and clinical trials after applying and comparing them to the ACR criteria in two multinational, multiethnic lupus cohorts. [ABSTRACT FROM PUBLISHER]

OBJECTIVE: To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. METHODS: Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). RESULTS: Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). CONCLUSION: Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To develop a measure of renal activity in systemic lupus erythematosus and use it to develop a renal response index. METHODS: Abstracted data from the medical records of 215 patients with lupus nephritis were sent to 8 nephrologists and 29 rheumatologists for rating. Seven nephrologists and 22 rheumatologists completed the ratings. Each physician rated each patient visit with respect to renal disease activity (none, mild, moderate, or severe). Using the most commonly selected rating for each patient as the gold standard, stepwise regression modeling was performed to identify the variables most related to renal disease activity, and these variables were then used to create an activity score. This activity score could then be applied to 2 consecutive visits to define a renal response index. RESULTS: The renal activity score was computed as follows: proteinuria 0.5-1 gm/day (3 points), proteinuria >1-3 gm/day (5 points), proteinuria >3 gm/day (11 points), urine red blood cell count >10/high-power field (3 points), and urine white blood cell count >10/high-power field (1 point). The chance-adjusted agreement between the renal response index derived from the activity score applied to the paired visits and the plurality physician response rating was 0.69 (95% confidence interval 0.59-0.79). CONCLUSION: Ratings derived from this index for rating of renal response showed reasonable agreement with physician ratings in a pilot study. The index will require further refinement, testing, and validation. A data-driven approach to create renal activity and renal response indices will be useful in both clinical care and research settings. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the degree to which physicians agree with each other and with ratings obtained with 3 existing responder indices, in rating the response to treatment of lupus nephritis. METHODS: Lupus nephritis patient medical records from 125 pairs of visits (6 months apart) were used to create renal response scenarios. Seven nephrologists and 22 rheumatologists rated each scenario as demonstrating complete response, partial response, same, or worsening. The plurality (most frequent) rating of renal response by the physicians was compared with the calculated score from the renal component of the British Isles Lupus Assessment Group (BILAG) index (original and updated [2004] version) and of the Responder Index for Lupus Erythematosus (RIFLE). The degree of agreement among the physicians was assessed by calculating intraclass correlation coefficients (ICCs). The degree of agreement between the plurality physician rating and ratings obtained with the established response indices was assessed using the kappa statistic. RESULTS: The ICC among all physicians was 0.64 (0.62 for nephrologists and 0.67 for rheumatologists). The chance-adjusted measure of agreement (kappa coefficient) between the plurality physician rating and the calculated score obtained using established indexes was 0.50 (95% confidence interval [95% CI] 0.38-0.61) for the RIFLE, 0.14 (95% CI 0.03-0.25) for the original BILAG, and 0.23 (95% CI 0.21-0.44) for the BILAG 2004. CONCLUSION: These findings indicate that rheumatologists as a group and nephrologists as a group have equal agreement in their rating of renal response. There was moderate agreement between plurality physician ratings and ratings obtained using the renal component of the RIFLE. Ratings of response using an index based on the original BILAG did not have good agreement with the plurality physician rating. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether shared epitope (SE)-containing HLA-DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome-wide) genetic admixture from the European population. METHODS: In this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti-cyclic citrullinated peptide (anti-CCP) antibodies and HLA-DRB1 genotyping, a panel of >1,200 ancestry-informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry. RESULTS: The frequency of SE-containing HLA-DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE-containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE-containing HLA-DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti-CCP antibody: 86 (48.9%) of 176 patients with anti-CCP antibody-positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti-CCP antibody-negative RA (P = 0.01, by chi-square test). CONCLUSION: HLA-DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which approximately 50-70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti-CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the impact of the patient's sex on the manifestations and outcome of systemic lupus erythematosus (SLE). METHODS: We studied SLE patients who were ages 16 years or older and had a disease duration of < or =5 years at the time of enrollment in the LUpus in MInorities, NAture versus nurture cohort, a multiethnic cohort consisting of Hispanic, African American, and Caucasian patients. Socioeconomic/demographic, clinical, and serologic features, as well as disease activity (by the Systemic Lupus Activity Measure, Revised) and damage accrual (by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were compared between male and female patient groups. Multivariable analyses using male sex and damage accrual as dependent variables were then performed. RESULTS: Sixty-three male SLE patients (10.2%) from all ethnic groups were included. The mean ages of the male and female patients were comparable. Factors that were either more frequent or tended to be more frequent among male SLE patients were Caucasian ethnicity, smoking, alcohol use, lupus anticoagulant (LAC) positivity, and renal involvement, whereas musculoskeletal involvement was less common. American College of Rheumatology criteria accrual time and disease duration were shorter in the male patients; damage was more common and of higher magnitude in this group. LAC positivity, shorter disease duration, and higher early damage scores were independently associated with male SLE. Male sex was a strong predictor of baseline damage, measured as a categorical variable (t-test = 2.357, beta-standardized coefficient 0.113; P = 0.019) or a continuous variable (hazard ratio 3.179 [95% confidence interval 1.999-5.056]; P < 0.001). Male sex was also positively associated with the development of damage over most of the course of the disease. CONCLUSION: Poorer long-term prognosis among men with SLE appears to be decisively determined by their accelerated development of damage, particularly early in the course of the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the clinical correlates of thrombocytopenia and the value of thrombocytopenia as a predictor of disease activity, damage accrual, and mortality in patients with systemic lupus erythematosus (SLE). METHODS: SLE patients participating in a longitudinal multiethnic cohort were studied. Thrombocytopenia was defined as a platelet count <100,000/mm(3) at or before enrollment (baseline). Patients were categorized by the presence and absence of thrombocytopenia. The impact of thrombocytopenia as well as severe thrombocytopenia (platelet count <50,000/mm(3)) on disease activity, damage accrual, and mortality was examined by multivariable analyses. RESULTS: A total of 616 patients were studied; 121 of the patients (20%) had thrombocytopenia, of whom 30 had severe thrombocytopenia. By univariable analyses, those with thrombocytopenia had more pulmonary, neurologic, renal, and hematologic involvement, worse disease activity and damage, and higher mortality rates. By multivariable analyses, thrombocytopenia was associated with higher disease activity over the disease course (P = 0.018), but not with the accrual of damage either at baseline (P = 0.543) or at the last visit (P = 0.086); however, severe thrombocytopenia was associated with damage accrual at the last visit (P = 0.020). When poverty was not included in the models, thrombocytopenia (<100,000/mm(3) or <50,000/mm(3)) was strongly associated with mortality (P < 0.001 for each comparison); however, the level of significance decreased some when poverty was included in the models. CONCLUSION: Thrombocytopenia early in the course of SLE is indicative of more severe and active disease. Severe thrombocytopenia is an independent predictor of damage accrual at the last visit. Thrombocytopenia is also an independent predictor of mortality, albeit of a lesser magnitude than that predicted by poverty. Patients with thrombocytopenia need close monitoring for possible undesirable outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). RESULTS: A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. CONCLUSION: Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study the association between deficient mannose-binding lectin (MBL) genotypes and arterial thrombotic events in systemic lupus erythematosus (SLE). METHODS: Patients with SLE of Hispanic, African American, and Caucasian ethnicity from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Arterial thrombotic events (myocardial infarction, angina, coronary artery bypass graft surgery, stroke, claudication, gangrene, or tissue loss and/or peripheral arterial thrombosis) that occurred after diagnosis were recorded. Genotyping for MBL gene polymorphisms was performed and their distribution was compared between patients who did and did not have thrombotic events. RESULTS: There were 58 events (21 cardiovascular, 27 cerebrovascular, and 10 peripheral vascular) in 48 patients. Patients who had thrombotic events were older and were more likely to be smokers, to have more severe disease, and to have accrued more damage overall. Also, a larger proportion of these patients had C-reactive protein values in the highest quintile of distribution. No significant difference in arterial thrombotic events was found in patients homozygous for MBL-deficient alleles compared with others. Similar results were seen within ethnic groups. Caucasians who developed potential thrombotic events exhibited a higher frequency of MBL-deficient alleles, but the difference was not statistically significant for all events together or for cardiovascular and cerebrovascular events combined. However, when only the cerebrovascular events were considered, the difference became statistically significant. CONCLUSION: Age, smoking, and measures of activity and damage were associated with arterial thrombotic events in patients with SLE, but MBL-deficient genotypes were not, with cerebrovascular events in Caucasians being the exception. The relationship between MBL-variant alleles and arterial thrombotic events may exist only within select ethnic groups and event types. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the clinical differences and the type and extent of organ damage in late- versus early-onset systemic lupus erythematosus (SLE). METHODS: A nested case-control study was performed in the context of LUMINA (LUpus in MInorities, NAture versus nurture), a large, longitudinal, multiethnic cohort. Patients who developed SLE at or after the age of 50 years were considered cases. Two controls (patients who developed SLE at age

OBJECTIVE: Venous thrombosis is a relatively frequent and serious complication in systemic lupus erythematosus (SLE) that has been associated with the presence of antiphospholipid antibodies (aPL). However, venous thrombotic events can also be seen in patients without aPL, and only a few patients with aPL develop venous thrombosis. This study was carried out to ascertain other factors contributing to the development of venous thrombosis in SLE. METHODS: Patients with SLE, ages > or = 16 years with < or = 5 years disease duration and of Hispanic, African American, or Caucasian ethnicity, from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Selected socioeconomic/demographic, clinical, laboratory, and treatment-exposure variables were compared between patients who developed and those who did not develop venous thrombotic events. Significant and clinically relevant variables were then entered into different multivariable models (Cox proportional hazards and unconditional stepwise logistic regression) to identify independent risk factors associated with the primary outcome. In another model, only patients who developed an event after enrollment (time 0) in the cohort were included. RESULTS: Of 570 LUMINA patients, 51 developed at least 1 venous thrombotic event after SLE diagnosis. In univariable analyses, smoking (P = 0.020), shorter disease duration at time 0 (P = 0.017), serum levels of total cholesterol, low-density lipoprotein, and triglycerides (all P < 0.0001), and presence of lupus anticoagulant (LAC) (P = 0.045) were associated with venous thrombotic events. Survival analyses showed a time-dependent significant association of the primary outcome with smoking (P = 0.008) and a borderline significant association with the presence of LAC (P = 0.070). Multivariable models showed an independent association with smoking, age at time 0, disease activity over time, LAC, mean dose of glucocorticoids, and shorter disease duration at time 0. CONCLUSION: Venous thrombotic events occur early in the course of SLE. Our data confirm the association between LAC and venous thrombotic events. Smoking, shorter disease duration, older age, disease activity over time, and higher mean daily glucocorticoid dose were identified as additional risk factors for the development of this vascular complication. These findings may have implications for the management of patients with SLE. [ABSTRACT FROM AUTHOR]

Background: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE).Objective: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE.Design: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002.Setting: 16 university-affiliated rheumatology clinics or practices in 11 U.S. states.Patients: 351 menopausal patients (mean age, 50 years) with inactive (81.5%) or stable-active (18.5%) SLE.Interventions: 12 months of treatment with active drug (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12 days per month) or placebo. The 12-month follow-up rate was 82% for the HRT group and 87% for the placebo group.Measurements: The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite.Results: Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95% CI for the treatment difference was 0.078, within the prespecified margin of 9% for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis.Limitations: Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis.Conclusions: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the differences in clinical manifestations, disease activity, damage accrual, and medication use in systemic lupus erythematosus (SLE) patients as a function of menopausal status at disease onset. METHODS: Women with SLE as per the criteria of the American College of Rheumatology, with disease duration of 6 months, and/or oophorectomy, and/or increased follicle-stimulating hormone values for reproductive-age women, and/or treatment with hormone replacement therapy. Patients were divided into premenopausal and postmenopausal categories. Socioeconomic status, cumulative clinical manifestations, disease activity (at study entry or time 0, last visit, and over time), as measured by the Systemic Lupus Activity Measure, and damage accrual, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (at time 0 and at last visit) were compared between the 2 groups of women. Multivariable models were then examined making adjustments for all possible known confounders. Dependent variables in the models were renal involvement, damage accrual, arterial vascular events, and venous thrombosis. RESULTS: Five hundred eighteen women from the LUMINA cohort were included; 436 (84.2%) were premenopausal and 82 (15.8%) were postmenopausal. Disease onset after menopause was more common among Caucasians. Renal involvement was more common in premenopausal women, whereas vascular arterial events were more frequent in postmenopausal women. All other disease manifestations, as well as disease activity, were comparable between both groups. The presence of damage accrual at time 0 and study end was more frequent in postmenopausal women. Age, rather than menopausal status, independently contributed to damage accrual, renal involvement, and vascular arterial events in these women. CONCLUSION: A hypoestrogenemic state secondary to menopause appears not to be protective against disease activity and damage accrual. Age rather than menopausal status is a strong independent predictor of damage accrual and of vascular events in women with lupus. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine whether hydroxychloroquine (HCQ) usage is associated with a reduced risk of damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: Patients (n = 518) meeting the American College of Rheumatology criteria for diagnosis of SLE and with

ObjectiveTo determine the prevalence of radiographic knee osteoarthritis (OA) as well as knee-related symptoms and functional limitations in female soccer players 12 years after an anterior cruciate ligament (ACL) injury.Methods Female soccer players who sustained an ACL injury 12 years earlier were examined with standardized weight-bearing knee radiography and 2 self-administered patient questionnaires, the Knee Injury and Osteoarthritis Outcome Score questionnaire and the Short Form 36-item health survey. Joint space narrowing and osteophytes were graded according to the radiographic atlas of the Osteoarthritis Research Society International. The cutoff value to define radiographic knee OA approximated a Kellgren/Lawrence grade of 2.Results Of the available cohort of 103 female soccer players, 84 (82%) answered the questionnaires and 67 (65%) consented to undergo knee radiography. The mean age at assessment was 31 years (range 26-40 years) and mean body mass index was 23 kg/m[2] (range 18-40 kg/m[2]). Fifty-five women (82%) had radiographic changes in their index knee, and 34 (51%) fulfilled the criterion for radiographic knee OA. Of the subjects answering the questionnaires, 63 (75%) reported having symptoms affecting their knee-related quality of life, and 28 (42%) were considered to have symptomatic radiographic knee OA. Slightly more than 60% of the players had undergone reconstructive surgery of the ACL. Using multivariate analyses, surgical reconstruction was found to have no significant influence on knee symptoms.Conclusion A very high prevalence of radiographic knee OA, pain, and functional limitations was observed in young women who sustained an ACL tear during soccer play 12 years earlier. These findings constitute a strong rationale to direct increased efforts toward prevention and better treatment of knee injury. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine if folinic acid supplementation during methotrexate (MTX) therapy for rheumatoid arthritis (RA) reduces both urinary 5-aminoimidazole-4-carboxamide (AICA) and urinary adenosine excretion more than does folic acid supplementation. AICA and adenosine are markers for MTX interference with purine metabolism. METHODS: Forty patients with RA who received MTX for 6 weeks were randomized to receive either daily folic acid or folinic acid supplements during an additional week of MTX therapy. Colorimetric and radioimmunocompetition assays were used to measure 24-hour urinary AICA and adenosine excretion levels, respectively. RESULTS: At the end of 6 weeks, 24-hour urinary levels of AICA, but not adenosine, were elevated as compared with baseline levels (i.e., prior to MTX therapy). Folinic acid, but not folic acid, supplementation normalized urinary AICA levels during MTX therapy. Relatively high urinary levels of AICA were correlated with reduced disease activity. No similar correlations were seen with urinary adenosine levels. CONCLUSION: The blockade of purine nucleotide biosynthesis by MTX at the AICA ribonucleotide transformylase-catalyzed step may be related to the efficacy of MTX, and this blockade is effectively relieved by folinic acid, but not by folic acid, supplementation. Copyright 2004 American College of Rheumatology [ABSTRACT FROM AUTHOR]

The aim of this study was to compare and contrast the clinical, immunogenetic and outcome features of two subgroups of Hispanic patients with systemic lupus erythematosus (SLE), one from Northern Spain (Spaniards) and one of from the USA (Hispano-Americans: Hispanics primarily of Mexican ancestry (Amerindian and Spaniard backgrounds). Patients with SLE as per the American College of Rheumatology classification criteria, from two University-affiliated Hospitals (Universidad de Cantabria) and disease of five or less years in duration (n = 28) and with four years of follow up constituted the Spaniard subgroup. Fifty-two patients of Hispano-American ancestry from the LUMINA (Lupus in Minority populations: Nature versus Nurture) cohort constituted the Hispano-American subgroup. Patients were studied using a similar protocol. In short, sociodemographic, clinical, immunological, immunogenetic and psychosocial and behavioral features were obtained at enrollment into the study (baseline visit) and yearly thereafter. The relationship between these variables and disease activity at baseline and over time, as measured by the systemic lupus activity measure (SLAM) and disease damage, as measured by the SLICC (Systemic Lupus International Collaborating Clinics) Damage Index (SDI) were determined. Variables found to be significant at P = 0.10 were then entered into multivariable linear regression models with disease activity at baseline and over time, and damage as the outcome measures. Patients of Hispano-American and Spaniard ethnicity had comparable sociodemographic features except for home density, which was higher among the Hispano-Americans. HLA-DRB1*08 was associated with SLE among the Hispano-Americans but not among the Spaniards. Hispano-American patients had more severe disease as manifested by more frequent clinical manifestations (renal and neurological), higher SLAM scores at baseline and over time and higher SDI scores at the year 4 visit (that despite the fact that Hispano-American patients had overall shorter disease duration than the Spaniard patients). Hispano-American ethnicity, younger age at disease onset and the number of ACR criteria at baseline and over time were consistently associated with disease activity, whereas increased home density and the absence of HLA-DRB1*0301 were significant predictors only overtime. Disease damage was associated with disease activity over time, the number of ACR criteria at baseline, increased home density and the presence of HLA-DRB1*08. This is the first longitudinal study of SLE in two different Hispanic subgroups. Hispanics with a strong Amerindian background have a more serious disease than that observed in Spaniards. Genetic and socio-economic differences between these two Hispanic subgroups probably account for these findings. [ABSTRACT FROM AUTHOR]