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1.  Vascular Complications of Systemic Sclerosis during Pregnancy 
Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by progressive fibrosis of the skin and visceral tissues as well as a noninflammatory vasculopathy. Vascular disease in systemic sclerosis is a major cause of morbidity and mortality among nonpregnant patients with SSc and is even a bigger concern in the pregnant SSc patient, as the underlying vasculopathy may prevent the required hemodynamic changes necessary to support a growing pregnancy. Vascular manifestations including scleroderma renal crisis and pulmonary arterial hypertension should be considered relative contraindications against pregnancy due to the high associations of both maternal and fetal morbidity and mortality. In contrast, Raynaud's phenomenon may actually improve somewhat during pregnancy. Women with SSc who are considering a pregnancy or discover they are pregnant require evaluation for the presence and extent of underlying vasculopathy. In the absence of significant visceral vasculopathy, most women with SSc can expect to have reasonable pregnancy outcomes.
doi:10.1155/2010/287248
PMCID: PMC2931377  PMID: 20814538
2.  Lifestyle Risk Factors Predict Disability and Death in Healthy Aging Adults 
The American Journal of Medicine  2012;125(2):190-197.
Background
Associations between modifiable health risk factors during middle age with disability and mortality in later life are critical to maximizing longevity while preserving function. Positive health effects of maintaining normal weight, routine exercise, and non-smoking are known for the short and intermediate term. We studied the effects of these risk factors into advanced age.
Methods
A cohort of 2,327 college alumnae ≥60 years was followed annually (1986–2005) by questionnaires addressing health risk factors, history, and Health Assessment Questionnaire disability (HAQ-DI). Mortality data were ascertained from the National Death Index. Low, medium, and high risk groups were created based upon the number (0, 1, ≥2) of health risk factors (overweight, smoking, inactivity) at baseline. Disability and mortality for each group were estimated from unadjusted data and regression analyses. Multivariable survival analyses estimated time to disability or death.
Results
Medium and high-risk groups had higher disability than the low risk group throughout the study (p<0.001). Low-risk subjects had onset of moderate disability delayed 8.3 years compared with high-risk. Mortality rates were higher in the high risk group (384 versus 247 per 10,000 person-years). Multivariable survival analyses showed the number of risk factors to be associated with cumulative disability and increased mortality.
Conclusions
Seniors with fewer behavioral risk factors during middle age have lower disability and improved survival. These data document that the associations of lifestyle risk factors upon health continue into the ninth decade.
doi:10.1016/j.amjmed.2011.08.006
PMCID: PMC3266548  PMID: 22269623
disability; aging; mortality; exercise; smoking; weight; longitudinal study
3.  Vitamin D Deficiency in a Multiethnic Healthy Control Cohort and Altered Immune Response in Vitamin D Deficient European-American Healthy Controls 
PLoS ONE  2014;9(4):e94500.
Objective
In recent years, vitamin D has been shown to possess a wide range of immunomodulatory effects. Although there is extensive amount of research on vitamin D, we lack a comprehensive understanding of the prevalence of vitamin D deficiency or the mechanism by which vitamin D regulates the human immune system. This study examined the prevalence and correlates of vitamin D deficiency and the relationship between vitamin D and the immune system in healthy individuals.
Methods
Healthy individuals (n = 774) comprised of European-Americans (EA, n = 470), African–Americans (AA, n = 125), and Native Americans (NA, n = 179) were screened for 25-hydroxyvitamin D [25(OH)D] levels by ELISA. To identify the most noticeable effects of vitamin D on the immune system, 20 EA individuals with severely deficient (<11.3 ng/mL) and sufficient (>24.8 ng/mL) vitamin D levels were matched and selected for further analysis. Serum cytokine level measurement, immune cell phenotyping, and phosphoflow cytometry were performed.
Results
Vitamin D sufficiency was observed in 37.5% of the study cohort. By multivariate analysis, AA, NA, and females with a high body mass index (BMI, >30) demonstrate higher rates of vitamin D deficiency (p<0.05). Individuals with vitamin D deficiency had significantly higher levels of serum GM-CSF (p = 0.04), decreased circulating activated CD4+ (p = 0.04) and CD8+ T (p = 0.04) cell frequencies than individuals with sufficient vitamin D levels.
Conclusion
A large portion of healthy individuals have vitamin D deficiency. These individuals have altered T and B cell responses, indicating that the absence of sufficient vitamin D levels could result in undesirable cellular and molecular alterations ultimately contributing to immune dysregulation.
doi:10.1371/journal.pone.0094500
PMCID: PMC3984168  PMID: 24727903
4.  Excess female siblings and male fetal loss in families with systemic lupus erythematosus 
The Journal of rheumatology  2013;40(4):430-434.
Background
Systemic lupus erythematosus (SLE) occurs more frequently among woman than men. We undertook the present study to determine whether the male-female ratio in SLE families is different than expected by chance, and whether excess male fetal loss is found.
Methods
All SLE patients met the revised American College of Rheumatology Classification criteria, while SLE-unaffected subjects were shown not to satisfy these same criteria. Putative family relationships were confirmed by genetic testing. Pregnancy history was obtained from all subjects, including unrelated control woman. Adjusted Wald binomial confidence intervals (CI) were calculated for ratio of boys to girls in families and compared to the expected ratio of 1.06
Results
There were 2578 subjects with SLE with 6056 siblings. Considering all subjects, we found 3201 boys and 5434 girls (ratio=0.59, of 95% CI 0.576–0.602). When considering only the SLE-unaffected siblings, there were 2919 boys and 3137 girls (ratio=0.93, 95%CI 0.92–0.94). In both cases, the ratio of males-to-females is statistically different than the known birth rate. Among SLE patients as well as among their sisters and mothers there was an excess of male fetal loss compared to the controls.
Conclusion
Siblings of SLE patients are more likely to be girls than expected. This finding may be in part explained by excess male fetal loss, which is found among SLE patients and their first degree relatives.
doi:10.3899/jrheum.120643
PMCID: PMC3693848  PMID: 23378464
Systemic lupus erythematosus; sex ratio; fetal loss; pregnancy
5.  Reduced Disability and Mortality among Aging Runners: a 21-year Longitudinal Study 
Archives of internal medicine  2008;168(15):1638-1646.
Background
Exercise has been shown to improve many health outcomes and well-being of people of all ages. Long-term studies in older adults are needed to confirm disability and survival benefits of exercise.
Methods
Annual self-administered questionnaires were sent to 538 members of a nationwide running club and 423 healthy controls from Northern California aged 50 years and older beginning in 1984. Data included running and exercise frequency, body mass index (BMI), and disability assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI scored 0–3) through 2005. 284 runners and 156 controls completed 21-years of follow-up. Causes of death through 2003 were ascertained using the National Death Index. Multivariable regression techniques compared groups on disability and mortality.
Results
At baseline, runners were younger, leaner, and less likely to smoke than controls. HAQ-DI was higher for controls than runners at all time points and increased with age in both groups, but to a lesser degree in runners (0.17, SD 0.34) than controls (0.36, SD 0.55, p<0.001). Multivariable analyses showed that runners had significantly lower risk of HAQ-DI=0.5 (HR 0.62, 95% CI 0.46–0.84). At 19 years, 15% of runners had died compared to 34% of controls. After adjustment for covariates, runners demonstrated a survival benefit (HR 0.61, 95% CI 0.45–0.82). Disability and survival curves continued to diverge between groups after 21-years of follow-up as participants approached their ninth decade of life.
Conclusions
Vigorous exercise (running) at middle and older ages is associated with reduced disability in later life and a notable survival advantage.
doi:10.1001/archinte.168.15.1638
PMCID: PMC3175643  PMID: 18695077
exercise; disability; aging; mortality; running; longitudinal study
6.  Pregnancy outcomes in systemic sclerosis, primary pulmonary hypertension, and sickle cell disease 
Obstetrics and gynecology  2008;111(4):927-934.
Purpose
Systemic sclerosis (SSc), primary pulmonary hypertension (PPH), and sickle cell disease (SCD) are uncommon vasculopathic diseases affecting women. We estimated the nationwide occurrence of pregnancies in women with these conditions and compared pregnancy outcomes to the general obstetric population.
Methods
We studied the 2002–2004 Nationwide Inpatient Sample (NIS), of the Healthcare Cost and Utilization Project to estimate the number of obstetric hospitalizations and deliveries among women with SSc, PPH, SCD, and the general population. Pregnancy outcomes included length of hospital stay (LOS), hypertensive disorders including preeclampsia (HTN), intrauterine growth restriction (IUGR), and cesarean delivery. Multivariable regression analyses were performed using maternal age, race/ethnicity, antiphospholipid antibody syndrome, diabetes mellitus, and renal failure as covariates.
Results
Of an estimated 11.2 million deliveries, 504 occurred in women with SSc, 182 with PPH, and 4,352 with SCD. SSc was associated with an increased risk of HTN (OR 3.71, 95%CI 2.25–6.15), IUGR (OR 3.74, 95%CI 1.51–9.28), and increased LOS. PPH was associated with an increase in the odds of antenatal hospitalization (OR 4.67, 95%CI 2.88–7.57), HTN (OR5.62, 95%CI 2.60–12.15) and a substantial increase in LOS. SCD was associated with an increased odds of antenatal hospitalization (OR 5.55, 95%CI 5.08–6.09), HTN (OR 1.78, 95%CI 1.48–2.14), and IUGR (OR 2.91, 95% CI 2.16–3.93), with a modest increase in LOS.
Conclusions
Women with SSc, PPH, and SCD have significantly increased rates of adverse pregnancy outcomes, requiring extensive preconceptional counseling about the risks of pregnancy. All pregnancies should be monitored closely for the development of complications.
doi:10.1097/01.AOG.0000308710.86880.a6
PMCID: PMC3171290  PMID: 18378753
Pregnancy; sickle cell disease; systemic sclerosis; pulmonary hypertension; outcomes; hospitalization
7.  Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus 
The Journal of Clinical Investigation  2013;123(12):5135-5145.
Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor–binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor–binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell–activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α–driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE.
doi:10.1172/JCI70231
PMCID: PMC3859403  PMID: 24270423
8.  Long Distance Running and Knee Osteoarthritis A Prospective Study 
Background
Prior studies of the relationship of physical activity to osteoarthritis (OA) of the knee have shown mixed results. The objective of this study was to determine if differences in the progression of knee OA in middle- to older-aged runners exist when compared with healthy nonrunners over nearly 2 decades of serial radiographic observation.
Methods
Forty-five long-distance runners and 53 controls with a mean age of 58 (range 50–72) years in 1984 were studied through 2002 with serial knee radiographs. Radiographic scores were two-reader averages for Total Knee Score (TKS) by modified Kellgren & Lawrence methods. TKS progression and the number of knees with severe OA were compared between runners and controls. Multivariate regression analyses were performed to assess the relationship between runner versus control status and radiographic outcomes using age, gender, BMI, education, and initial radiographic and disability scores among covariates.
Results
Most subjects showed little initial radiographic OA (6.7% of runners and 0 controls); however, by the end of the study runners did not have more prevalent OA (20 vs 32%, p =0.25) nor more cases of severe OA (2.2% vs 9.4%, p=0.21) than did controls. Regression models found higher initial BMI, initial radiographic damage, and greater time from initial radiograph to be associated with worse radiographic OA at the final assessment; no significant associations were seen with gender, education, previous knee injury, or mean exercise time.
Conclusions
Long-distance running among healthy older individuals was not associated with accelerated radiographic OA. These data raise the possibility that severe OA may not be more common among runners.
doi:10.1016/j.amepre.2008.03.032
PMCID: PMC2556152  PMID: 18550323
9.  Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort 
Autoimmune Diseases  2012;2012:819634.
Purpose. This study evaluates high-throughput autoantibody screening and determines associated systemic lupus erythematosus (SLE) clinical features in a large lupus cohort. Methods. Clinical and demographic information, along with serum samples, were obtained from each SLE study participant after appropriate informed consent. Serum samples were screened for 10 distinct SLE autoantibody specificities and examined for association with SLE ACR criteria and subcriteria using conditional logistic regression analysis. Results. In European-American SLE patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients with proteinuria. In African-American SLE patients, cellular casts associate with autoantibodies against dsDNA, Sm, and Sm/nRNP. Conclusion. Using a high-throughput, bead-based method of autoantibody detection, anti-dsDNA is significantly enriched in patienets with SLE ACR renal criteria as has been previously described. However, lymphopenia is associated with several distinct autoantibody specificities. These findings offer meaningful information to allow clinicians and clinical investigators to understand which autoantibodies correlate with select SLE clinical manifestations across common racial groups using this novel methodology which is expanding in clinical use.
doi:10.1155/2012/819634
PMCID: PMC3439936  PMID: 22988489
10.  Fibromyalgia, Systemic Lupus Erythematosus (SLE) and the Evaluation of SLE Activity 
The Journal of rheumatology  2009;36(1):82-88.
Purpose
To determine if fibromyalgia or fibromyalgianess is increased in SLE compared with non-SLE patients, whether fibromyalgia or fibromyalgianess (the tendency to respond to illness and psychosocial stress with fatigue, widespread pain, general increase in symptoms and similar factors ) biases the Systemic Lupus Erythematosus Activity Questionnaire (SLAQ), and to determine if the SLAQ is overly sensitive to fibromyalgia symptoms.
Method
We developed a 16-item SLE symptom scale (SLESS) modeled on the SLAQ and used that scale to investigate the relation between SLE symptoms and fibromyalgianess in 23,321 rheumatic disease patients. Fibromyalgia was diagnosed by survey fibromyalgia criteria and fibromyalgianess was measured using the Symptom Intensity Scale (SI). As comparison groups, we combined patients with rheumatoid arthritis (RA) and non-inflammatory rheumatic disorders into an “arthritis” group and also utilized a physician-diagnosed group of fibromyalgia patients.
Results
Fibromyalgia was identified in 22.1% of SLE and 17.0% of those with arthritis. The SI scale was minimally increased in SLE. The correlation between SLAQ and SLESS was 0.738. SLESS/SLAQ scale items: Raynaud’s, rash, fever, easy bruising and hair loss were significantly more associated with SLE than fibromyalgia, while the reverse was true for headache, abdominal pain, paresthesias/stroke, fatigue, cognitive problems and muscle pain or weakness. There was no evidence of a disproportionate symptom reporting associated with fibromyalgianess. Self-reported SLE was associated with an increased prevalence of fibromyalgia when unconfirmed by physicians compared to SLE confirmed by physicians.
Conclusions
The prevalence of fibromyalgia in SLE is minimally increased compared with its prevalence in patients with arthritis. Fibromyalgianess does not bias the SLESS and should not bias SLE assessments, including the SLAQ.
doi:10.3899/jrheum.080212
PMCID: PMC2944223  PMID: 19004039
Systemic Lupus Erythematosus; Fibromyalgia; Systemic Lupus Erythematosus Activity Questionnaire; SLAQ; SLAM
11.  Prevalence of Adult Systemic Lupus Erythematosus in California and Pennsylvania in 2000: Estimates Using Hospitalization Data 
Arthritis and rheumatism  2007;56(6):2092-2094.
doi:10.1002/art.22641
PMCID: PMC2530907  PMID: 17530651
Systemic lupus erythematosus; prevalence; epidemiology; ethnicity; gender; age
12.  A randomized, controlled trial of interferon-β-1a (Avonex®) in patients with rheumatoid arthritis: a pilot study [ISRCTN03626626] 
Arthritis Research & Therapy  2003;6(1):R73-R77.
The objective of this study was to evaluate the safety and possible efficacy of IFN-β-1a for the treatment of patients with rheumatoid arthritis (RA). Twenty-two patients with active RA were enrolled in a phase II randomized, double-blind, placebo-controlled trial of 30 μg IFN-β-1a by weekly self-injection for 24 weeks. The primary outcome of the study was safety. Secondary outcomes included the proportion of patients achieving an American College of Rheumatology (ACR) 20 response at 24 weeks. There were no significant differences in adverse events reported in the two groups. Fewer than 20% of patients in each arm of the study achieved an ACR 20 response at 24 weeks (P = 0.71). Sixty-nine percent of patients receiving IFN-β and 67% receiving placebo terminated the study early, most of them secondary to a perceived lack of efficacy. Overall, IFN-β-1a had a safety profile similar to that of placebo. There were no significant differences in the proportion of patients achieving an ACR 20 response between the two groups.
doi:10.1186/ar1026
PMCID: PMC400417  PMID: 14979940
clinical trials; cytokines; interferon-β; rheumatoid arthritis; therapy

Results 1-12 (12)