Bio

Clinical Focus


  • Pediatric Rheumatology

Academic Appointments


Administrative Appointments


  • Vice President of Medical Affairs, Lucile Packard Children's Hospital at Stanford (2012 - Present)
  • Associate Chair, Department of Pediatrics (2008 - Present)
  • Chief of Staff, Lucile Packard Children's Hospital at Stanford (2008 - 2012)
  • Co-Director, Spectrum Child Health, Lucile Packard Children's Hospital and Stanford School of Medicine (2005 - Present)
  • Immediate Past Chair, Childhood Arthritis and Rheumatology Research Alliance (CARRA), Stanford (2007 - 2010)
  • Chief of Pediatric Rheumatology, Stanford (1997 - 2012)

Professional Education


  • Board Certification: Pediatrics, American Board of Pediatrics (1984)
  • Residency:Children's Hospital Los Angeles (1979) CA
  • Board Certification: Pediatric Rheumatology, American Board of Pediatrics (1992)
  • Fellowship:Children's Hospital (1981) CA
  • Medical Education:UCLA School of Medicine (1977) CA
  • MD, UCLA, Medicine (1977)

Research & Scholarship

Current Research and Scholarly Interests


The major emphasis of my work in the past decade has been focused on the future of academic pediatrics and pediatric rheumatology through providing training, research opportunities and environments to nurture and challenge future pediatric rheumatologists and subspecialists, and has now expanded to encompass design of new models of care for children with complex chronic illness

In the area of pediatric rheumatology, I am a founder of the pediatric research rheumatology
research network (Childhood Arthritis and Rheumatology Research Alliance -CARRA) which now includes the vast majority of practicing pediatric rheumatologists and trainees in the US and Canada with over 270 members and 91 sites. The network supports 15-20 studies and trials and currently has 4 major NIH clinical trials, and 2 ARRA funded projects (one RC1 in Clinical Effectiveness Research, and one RC2 to develop a pediatric rheumatic disease registry). The clinical trials include Atherosclerosis Prevention in Pediatric Lupus Erythematosus--APPLE, Trial of Early Agressive Treatment of polyarticular JIA--TREAT JIA, Randomized Placebo Phase of Rilonacept Treatment in systemic JIA (RAPPORT), and Rituximab in Myositis (RIM).

At Stanford, I have focused my scholarly work on developing programs to enhance career development of faculty and trainees. Through my role as co-director of the pediatric portion of Stanford's CTSA, Spectrum Child Health, we have developed programs for mentoring, career development, and clinical research personnel support. for child health clinical and translational research investigators. In addition, Hannah Valantine MD, Senior Associate Dean of Diversity and Leadership, and I are collaborating on new approaches to improving the academic success and retention of women and young family-oriented faculty, through a variety of programs and research on stereotype threat, flexibilty in careers, and the role of clinical excellence in our faculty lines.

Since early 2011, I have expanded my interest to encompass health care delivery, extending my interest in children with rheumatic chronic illness to broadly study the most complex and highest cost children across all diagnoses. . LPCH, a high quality tertiary and quaternary institution, provides an outstanding venue to study and test innovative models of care with an emphasis on the most complex and chronically ill children, with very high costs of care. The rich collaboration between pediatric faculty and researchers--Lee Sanders, John Mark, David Bergman, Ken Cox and others, with LPCH leaders, Alexandria Combs, Karen Wayman, Doug Cameron and many others, and a hybrid strategy firm Jump Associates, has led to the design of the Children's Complex Care Model, which is currently in pilot testing. The basic premis of the model is to cxreate true partnerships between patients and families, providers --both subspecialty and primary care providers, and the community to improve the quality and outcomes while decreasing costs across the entire continuum of care.

Clinical Trials


  • Safety and Effectiveness of Rilonacept for Treating Systemic Juvenile Idiopathic Arthritis in Children and Young Adults Not Recruiting

    Systemic juvenile idiopathic arthritis (SJIA) is a type of arthritis that typically occurs before 16 years of age. SJIA usually involves heat, pain, swelling, and stiffness in the body's joints. It can also involve fever, rash, anemia, and inflammation in various parts of the body. Rilonacept is a drug that can reduce inflammation. The purpose of this study is to determine whether a rilonacept drug regimen initiated early is more effective than a similar rilonacept drug regimen initiated 4 weeks later when treating children and young adults with SJIA.

    Stanford is currently not accepting patients for this trial. For more information, please contact Christy Sandborg, (650) 723 - 8295.

    View full details

Teaching

2013-14 Courses


Publications

Journal Articles


  • Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein. Annals of the rheumatic diseases Ardoin, S. P., Schanberg, L. E., Sandborg, C. I., Barnhart, H. X., Evans, G. W., Yow, E., Mieszkalski, K. L., Ilowite, N. T., Eberhard, A., Imundo, L. F., Kimura, Y., Levy, D., von Scheven, E., Silverman, E., Bowyer, S. L., Punaro, L., Singer, N. G., Sherry, D. D., McCurdy, D. K., Klein-Gitelman, M., Wallace, C., Silver, R. M., Wagner-Weiner, L., Higgins, G. C., Brunner, H. I., Jung, L., Soep, J. B., Reed, A. M., Thompson, S. D. 2014; 73 (3): 557-566

    Abstract

    OBJECTIVE: Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy. METHODS: Subgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score ≥4 as post-pubertal or <4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or <110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or <1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models. RESULTS: Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures. CONCLUSIONS: Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy. CLINICALTRIALS.GOV IDENTIFIER:: NCT00065806.

    View details for DOI 10.1136/annrheumdis-2012-202315

    View details for PubMedID 23436914

  • Shrinking Lung Syndrome as a Manifestation of Pleuritis: A New Model Based on Pulmonary Physiological Studies JOURNAL OF RHEUMATOLOGY Henderson, L. A., Loring, S. H., Gill, R. R., Liao, K. P., Ishizawar, R., Kim, S., Perlmutter-Goldenson, R., Rothman, D., Son, M. B., Stoll, M. L., Zemel, L. S., Sandborg, C., Dellaripa, P. F., Nigrovic, P. A. 2013; 40 (3): 273-281

    Abstract

    The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients.Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantify lung volume and parenchymal density.Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging results were free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39%-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density.Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with 2 characteristic physiological abnormalities: (1) impaired respiratory force at high but not low lung volumes; and (2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example through neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.

    View details for DOI 10.3899/jrheum.121048

    View details for Web of Science ID 000316527500011

    View details for PubMedID 23378468

  • An i2b2-based, generalizable, open source, self-scaling chronic disease registry JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION Natter, M. D., Quan, J., Ortiz, D. M., Bousvaros, A., Ilowite, N. T., Inman, C. J., Marsolo, K., McMurry, A. J., Sandborg, C. I., Schanberg, L. E., Wallace, C. A., Warren, R. W., Weber, G. M., Mandl, K. D. 2013; 20 (1): 172-179

    Abstract

    Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software.Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions.The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA.We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing.The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases.

    View details for DOI 10.1136/amiajnl-2012-001042

    View details for Web of Science ID 000313512900028

    View details for PubMedID 22733975

  • A New Era in the Treatment of Systemic Juvenile Idiopathic Arthritis NEW ENGLAND JOURNAL OF MEDICINE Sandborg, C., Mellins, E. D. 2012; 367 (25): 2439-2440

    View details for DOI 10.1056/NEJMe1212640

    View details for Web of Science ID 000312531600015

    View details for PubMedID 23252530

  • Correlation analyses of clinical and molecular findings identify candidate biological pathways in systemic juvenile idiopathic arthritis BMC MEDICINE Ling, X. B., Macaubas, C., Alexander, H. C., Wen, Q., Chen, E., Peng, S., Sun, Y., Deshpande, C., Pan, K., Lin, R., Lih, C., Chang, S. P., Lee, T., Sandborg, C., Begovich, A. B., Cohen, S. N., Mellins, E. D. 2012; 10

    Abstract

    Clinicians have long appreciated the distinct phenotype of systemic juvenile idiopathic arthritis (SJIA) compared to polyarticular juvenile idiopathic arthritis (POLY). We hypothesized that gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with each disease would reveal distinct biological pathways when analyzed for significant associations with elevations in two markers of JIA activity, erythrocyte sedimentation rate (ESR) and number of affected joints (joint count, JC).PBMC RNA from SJIA and POLY patients was profiled by kinetic PCR to analyze expression of 181 genes, selected for relevance to immune response pathways. Pearson correlation and Student's t-test analyses were performed to identify transcripts significantly associated with clinical parameters (ESR and JC) in SJIA or POLY samples. These transcripts were used to find related biological pathways.Combining Pearson and t-test analyses, we found 91 ESR-related and 92 JC-related genes in SJIA. For POLY, 20 ESR-related and 0 JC-related genes were found. Using Ingenuity Systems Pathways Analysis, we identified SJIA ESR-related and JC-related pathways. The two sets of pathways are strongly correlated. In contrast, there is a weaker correlation between SJIA and POLY ESR-related pathways. Notably, distinct biological processes were found to correlate with JC in samples from the earlier systemic plus arthritic phase (SAF) of SJIA compared to samples from the later arthritis-predominant phase (AF). Within the SJIA SAF group, IL-10 expression was related to JC, whereas lack of IL-4 appeared to characterize the chronic arthritis (AF) subgroup.The strong correlation between pathways implicated in elevations of both ESR and JC in SJIA argues that the systemic and arthritic components of the disease are related mechanistically. Inflammatory pathways in SJIA are distinct from those in POLY course JIA, consistent with differences in clinically appreciated target organs. The limited number of ESR-related SJIA genes that also are associated with elevations of ESR in POLY implies that the SJIA associations are specific for SJIA, at least to some degree. The distinct pathways associated with arthritis in early and late SJIA raise the possibility that different immunobiology underlies arthritis over the course of SJIA.

    View details for DOI 10.1186/1741-7015-10-125

    View details for Web of Science ID 000312394300001

    View details for PubMedID 23092393

  • Algorithm development for corticosteroid management in systemic juvenile idiopathic arthritis trial using consensus methodology PEDIATRIC RHEUMATOLOGY Ilowite, N. T., Sandborg, C. I., Feldman, B. M., Grom, A., Schanberg, L. E., Giannini, E. H., Wallace, C. A., Schneider, R., Kenney, K., Gottlieb, B., Hashkes, P. J., Imundo, L., Kimura, Y., Lang, B., Miller, M., Milojevic, D., O'Neil, K. M., Punaro, M., Ruth, N., Singer, N. G., Vehe, R. K., Verbsky, J., Woodward, A., Zemel, L. 2012; 10

    Abstract

    The management of background corticosteroid therapy in rheumatology clinical trials poses a major challenge. We describe the consensus methodology used to design an algorithm to standardize changes in corticosteroid dosing during the Randomized Placebo Phase Study of Rilonacept in Systemic Juvenile Idiopathic Arthritis Trial (RAPPORT).The 20 RAPPORT site principal investigators (PIs) and 4 topic specialists constituted an expert panel that participated in the consensus process. The panel used a modified Delphi Method consisting of an on-line questionnaire, followed by a one day face-to-face consensus conference. Consensus was defined as ? 75% agreement. For items deemed essential but when consensus on critical values was not achieved, simple majority vote drove the final decision.The panel identified criteria for initiating or increasing corticosteroids. These included the presence or development of anemia, myocarditis, pericarditis, pleuritis, peritonitis, and either complete or incomplete macrophage activation syndrome (MAS). The panel also identified criteria for tapering corticosteroids which included absence of fever for ? 3?days in the previous week, absence of poor physical functioning, and seven laboratory criteria. A tapering schedule was also defined.The expert panel established consensus regarding corticosteroid management and an algorithm for steroid dosing that was well accepted and used by RAPPORT investigators. Developed specifically for the RAPPORT trial, further study of the algorithm is needed before recommendation for more general clinical use.

    View details for DOI 10.1186/1546-0096-10-31

    View details for Web of Science ID 000312638100001

    View details for PubMedID 22931206

  • European ancestry decreases the risk of early onset, severe lupus nephritis in a single center, multiethnic pediatric lupus inception cohort LUPUS Frankovich, J. D., Hsu, J. J., Sandborg, C. I. 2012; 21 (4): 421-429

    Abstract

    To determine whether pediatric SLE patients without European ancestry are at higher risk for development of severe lupus nephritis (ISN/RPS class III, IV or V).Ninety-eight of 101 patients with pediatric SLE (age <18 years at diagnosis) were enrolled. Race/ethnicity of four grandparents, socioeconomic status (SES) and language proficiency were collected. The primary outcome was time to development of severe lupus nephritis.Based on patient report of four grandparent ancestry, 29% had at least one grandparent of European ancestry (14% had all four grandparents of European ancestry). Patients without European ancestry were 46% Hispanic, 47% Asian, and 3% African American. In the entire 98 patient cohort, 12% had ?3 different ancestries. Patients without European ancestry had significantly lower SES levels and English proficiency. There was no significant difference between patients with or without European ancestry in duration of SLE, age of onset, and lag time between symptoms and diagnosis. Patients with at least one grandparent of European ancestry had a decreased risk of developing severe lupus nephritis, which remained significant after controlling for age, gender, SES and English proficiency (hazard ratio 0.4, 95% confidence interval 0.2-0.9).This study demonstrates that presence of at least one grandparent of European ancestry decreases the risk of severe lupus nephritis, a finding that is not explained by measurable socioeconomic differences and language barriers.

    View details for DOI 10.1177/0961203312437805

    View details for Web of Science ID 000301583400008

    View details for PubMedID 22427363

  • Use of atorvastatin in systemic lupus erythematosus in children and adolescents ARTHRITIS AND RHEUMATISM Schanberg, L. E., Sandborg, C., Barnhart, H. X., Ardoin, S. P., Yow, E., Evans, G. W., Mieszkalski, K. L., Ilowite, N. T., Eberhard, A., Imundo, L. F., Kimura, Y., von Scheven, E., Silverman, E., Bowyer, S. L., Punaro, M., Singer, N. G., Sherry, D. D., McCurdy, D., Klein-Gitelman, M., Wallace, C., Silver, R., Wagner-Weiner, L., Higgins, G. C., Brunner, H. I., JUNG, L., Soep, J. B., Reed, A. M., Provenzale, J., Thompson, S. D. 2012; 64 (1): 285-296

    Abstract

    Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE.A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n=113) or placebo (n=108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes.Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). The atorvastatin group achieved lower hsCRP (P=0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups.Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.

    View details for DOI 10.1002/art.30645

    View details for Web of Science ID 000298598100035

    View details for PubMedID 22031171

  • Implementing an Interoperable Personal Health Record in Pediatrics: Lessons Learned at an Academic Children's Hospital. Journal of participatory medicine Anoshiravani, A., Gaskin, G., Kopetsky, E., Sandborg, C., Longhurst, C. A. 2011; 3

    Abstract

    This paper describes the development of an innovative health information technology creating a bidirectional link between the electronic medical record (EMR) of an academic children's hospital and a commercially available, interoperable personal health record (PHR). The goal of the PHR project has been to empower pediatric patients and their families to play a more active role in understanding, accessing, maintaining, and sharing their personal health information to ultimately improve health outcomes. The most notable challenges proved more operational and cultural than technological. Our experience demonstrates that an interoperable PHR is technically and culturally achievable at a pediatric academic medical center. Recognizing the complex social, cultural, and organizational contexts of these systems is important for overcoming barriers to a successful implementation.

    View details for PubMedID 21853160

  • Plasma profiles in active systemic juvenile idiopathic arthritis: Biomarkers and biological implications PROTEOMICS Ling, X. B., Park, J. L., Carroll, T., Nguyen, K. D., Lau, K., Macaubas, C., Chen, E., Lee, T., Sandborg, C., Milojevic, D., Kanegaye, J. T., Gao, S., Burns, J., Schilling, J., Mellins, E. D. 2010; 10 (24): 4415-4430

    Abstract

    Systemic juvenile idiopathic arthritis (SJIA) is a chronic arthritis of children characterized by a combination of arthritis and systemic inflammation. There is usually non-specific laboratory evidence of inflammation at diagnosis but no diagnostic test. Normalized volumes from 89/889 2-D protein spots representing 26 proteins revealed a plasma pattern that distinguishes SJIA flare from quiescence. Highly discriminating spots derived from 15 proteins constitute a robust SJIA flare signature and show specificity for SJIA flare in comparison to active polyarticular juvenile idiopathic arthritis or acute febrile illness. We used 7 available ELISA assays, including one to the complex of S100A8/S100A9, to measure levels of 8 of the15 proteins. Validating our DIGE results, this ELISA panel correctly classified independent SJIA flare samples, and distinguished them from acute febrile illness. Notably, data using the panel suggest its ability to improve on erythrocyte sedimentation rate or C-reactive protein or S100A8/S100A9, either alone or in combination in SJIA F/Q discriminations. Our results also support the panel's potential clinical utility as a predictor of incipient flare (within 9?wk) in SJIA subjects with clinically inactive disease. Pathway analyses of the 15 proteins in the SJIA flare versus quiescence signature corroborate growing evidence for a key role for IL-1 at disease flare.

    View details for DOI 10.1002/pmic.201000298

    View details for Web of Science ID 000285882200008

    View details for PubMedID 21136595

  • Behcet's disease and heart transplantation: A word of caution JOURNAL OF HEART AND LUNG TRANSPLANTATION Hollander, S. A., Yasnovsky, J. R., Reinhartz, O., Chan, F., Sandborg, C., Hunt, S., Bernstein, D., Chin, C. 2010; 29 (11): 1306-1308

    Abstract

    Behcet's disease is a rare autoimmune disease characterized by oral and genital ulcers, and by multisystem disease, including arthritis, neurologic complications and vasculitis. Large-vessel and coronary artery aneurysms are often an indication for surgery, but the return of aneurysms, thrombosis, and the tendency to exhibit an exaggerated inflammatory response at puncture sites (pathergy) complicate surgical recovery. As such, cardiac transplantation, which requires atrial and large-vessel anastomoses, has not been reported in patients with Behcet's disease. We report the first orthotopic heart transplant with >1-year survival in a patient with Behcet's disease despite major complications. The investigators remain pessimistic about cardiac transplantation in patients with Behcet's disease until advances in preventing recurrent vascular pathology ensue.

    View details for DOI 10.1016/j.healun.2010.07.010

    View details for Web of Science ID 000284030700015

    View details for PubMedID 20822920

  • Living Profiles: Design of a health media platform for teens with special healthcare needs JOURNAL OF BIOMEDICAL INFORMATICS Chira, P., Nugent, L., Miller, K., Park, T., Donahue, S., Soni, A., Nugent, D., Sandborg, C. 2010; 43 (5): S9-S12

    Abstract

    Living Profiles is a health media platform in development that aggregates multiple data flows to help teens with special healthcare needs (SHCN), particularly with regard to self-management and independence. A teen-oriented personal health record (PHR) incorporates typical teen behaviors and attitudes about health and wellness, encompasses how teens perceive and convey quality of life, and aligns with data related to their chronic medical condition. We have conceived a secure personalized user interface called the Quality of Life Timeline, which will assist with the transition from pediatric care to an adult provider through modules that include a mood meter, reminder device, and teleport medicine. With this personalized PHR, teens with SHCN can better understand their condition and its effects on daily activities and life goals and vice versa; additionally, use of this PHR allows for better information sharing and communication between providers and patients. The use of a teen-oriented tool such as Living Profiles can impact teens' overall quality of life and disease self-management, important attributes for a successful transition program.

    View details for DOI 10.1016/j.jbi.2010.05.008

    View details for Web of Science ID 000293686500004

    View details for PubMedID 20937487

  • Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort LUPUS Ardoin, S. P., Schanberg, L. E., Sandborg, C., Yow, E., Barnhart, H. X., Mieszkalski, K. L., Ilowite, N. T., von Scheven, E., Eberhard, A., Levy, D. M., Kimura, Y., Silverman, E., Bowyer, S. L., Punaro, L., Singer, N. G., Sherry, D. D., McCurdy, D., Klein-Gitelman, M., Wallace, C., Silver, R., Wagner-Weiner, L., Higgins, G. C., Brunner, H. I., Jung, L. K., Imundo, L., Soep, J. B., Reed, A. M. 2010; 19 (11): 1315-1325

    Abstract

    As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

    View details for DOI 10.1177/0961203310373937

    View details for Web of Science ID 000282090700007

    View details for PubMedID 20861207

  • Decrease in Hospital-wide Mortality Rate After Implementation of a Commercially Sold Computerized Physician Order Entry System PEDIATRICS Longhurst, C. A., Parast, L., Sandborg, C. I., Widen, E., Sullivan, J., Hahn, J. S., Dawes, C. G., Sharek, P. J. 2010; 126 (1): 14-21

    Abstract

    Implementations of computerized physician order entry (CPOE) systems have previously been associated with either an increase or no change in hospital-wide mortality rates of inpatients. Despite widespread enthusiasm for CPOE as a tool to help transform quality and patient safety, no published studies to date have associated CPOE implementation with significant reductions in hospital-wide mortality rates.The objective of this study was to determine the effect on the hospital-wide mortality rate after implementation of CPOE at an academic children's hospital.We performed a cohort study with historical controls at a 303-bed, freestanding, quaternary care academic children's hospital. All nonobstetric inpatients admitted between January 1, 2001, and April 30, 2009, were included. A total of 80,063 patient discharges were evaluated before the intervention (before November 1, 2007), and 17,432 patient discharges were evaluated after the intervention (on or after November 1, 2007). On November 4, 2007, the hospital implemented locally modified functionality within a commercially sold electronic medical record to support CPOE and electronic nursing documentation.After CPOE implementation, the mean monthly adjusted mortality rate decreased by 20% (1.008-0.716 deaths per 100 discharges per month unadjusted [95% confidence interval: 0.8%-40%]; P = .03). With observed versus expected mortality-rate estimates, these data suggest that our CPOE implementation could have resulted in 36 fewer deaths over the 18-month postimplementation time frame.Implementation of a locally modified, commercially sold CPOE system was associated with a statistically significant reduction in the hospital-wide mortality rate at a quaternary care academic children's hospital.

    View details for DOI 10.1542/peds.2009-3271

    View details for Web of Science ID 000279431000003

    View details for PubMedID 20439590

  • PEDIATRIC RHEUMATIC DISEASE Standards of care for JIA-the basic foundation for quality NATURE REVIEWS RHEUMATOLOGY Sandborg, C. 2010; 6 (7): 389-390

    View details for DOI 10.1038/nrrheum.2010.98

    View details for Web of Science ID 000279428500004

    View details for PubMedID 20596052

  • Distribution of circulating cells in systemic juvenile idiopathic arthritis across disease activity states CLINICAL IMMUNOLOGY Macaubas, C., Nguyen, K., Deshpande, C., Phillips, C., Peck, A., Lee, T., Park, J. L., Sandborg, C., Mellins, E. D. 2010; 134 (2): 206-216

    Abstract

    Juvenile idiopathic arthritis (JIA) encompasses a group of chronic childhood arthritides of unknown etiology. One subtype, systemic JIA (SJIA), is characterized by a combination of arthritis and systemic inflammation. Its systemic nature suggests that clues to SJIA pathogenesis may be found in examination of peripheral blood cells. To determine the immunophenotypic profiles of circulating mononuclear cells in SJIA patients with different degrees of disease activity, we studied PBMC from 31 SJIA patients, 20 polyarticular JIA patients (similar to adult rheumatoid arthritis), and 31 age-matched controls. During SJIA disease flare, blood monocyte numbers were increased, whereas levels of myeloid dendritic cells (DC) and gammadelta T cells were reduced. At both flare and quiescence, increased levels of CD14 and CD16 were found on SJIA monocytes. Levels of CD16-DC were elevated at SJIA quiescence compared both to healthy controls and to SJIA subjects with active disease. Overall, our findings suggest dysregulation of innate immunity in SJIA and raise the possibility that quiescence represents a state of compensated inflammation.

    View details for DOI 10.1016/j.clim.2009.09.010

    View details for Web of Science ID 000273701800013

    View details for PubMedID 19879195

  • Premature Atherosclerosis in Pediatric Systemic Lupus Erythematosus ARTHRITIS AND RHEUMATISM Schanberg, L. E., Sandborg, C., Barnhart, H. X., Ardoin, S. P., Yow, E., Evans, G. W., Mieszkalski, K. L., Ilowite, N. T., Eberhard, A., Levy, D. M., Kimura, Y., von Scheven, E., Silverman, E., Bowyer, S. L., Punaro, L., Singer, N. G., Sherry, D. D., McCurdy, D., Klein-Gitelman, M., Wallace, C., Silver, R., Wagner-Weiner, L., Higgins, G. C., Brunner, H. I., Jung, L., Soep, J. B., Reed, A. 2009; 60 (5): 1496-1507

    Abstract

    To evaluate risk factors for subclinical atherosclerosis in a population of patients with pediatric systemic lupus erythematosus (SLE).In a prospective multicenter study, a cohort of 221 patients underwent baseline measurements of carotid intima-media thickness (CIMT) as part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE disease measures, medications, and traditional risk factors for atherosclerosis were assessed. A standardized protocol was used to assess the thickness of the bilateral common carotid arteries and the mean maximal IMT of 12 segments. Univariable analysis identified potential associations with CIMT, which were examined in multivariable linear regression modeling.Based on the mean-mean common or the mean-max CIMT as the dependent variable, univariable analysis showed significant associations of the following variables with increased CIMT: increasing age, longer SLE duration, minority status, higher body mass index (BMI), male sex, increased creatinine clearance, higher lipoprotein(a) level, proteinuria, azathioprine treatment, and prednisone dose. In multivariable modeling, both azathioprine use (P=0.005 for the mean-mean model and P=0.102 for the mean-max model) and male sex (P<0.001) were associated with increases in the mean-max CIMT. A moderate dosage of prednisone (0.15-0.4 mg/kg/day) was associated with decreases in the mean-max CIMT (P=0.024), while high-dose and low-dose prednisone were associated with increases in the mean-mean common CIMT (P=0.021) and the mean-max CIMT (P=0.064), respectively. BMI (P<0.001) and creatinine clearance (P=0.031) remained associated with increased mean-mean common CIMT, while increasing age (P<0.001) and increasing lipoprotein(a) level (P=0.005) were associated with increased mean-max CIMT.Traditional as well as nontraditional risk factors were associated with increased CIMT in this cohort of patients in the APPLE trial. Azathioprine treatment was associated with increased CIMT. The relationship between CIMT and prednisone dose may not be linear.

    View details for DOI 10.1002/art.24469

    View details for Web of Science ID 000266071700036

    View details for PubMedID 19404953

  • Adalimumab with or without methotrexate in juvenile rheumatoid arthritis NEW ENGLAND JOURNAL OF MEDICINE Lovell, D. J., Ruperto, N., Goodman, S., Reiff, A., Jung, L., Jarosova, K., Nemcova, D., Mouy, R., Sandborg, C., Bohnsack, J., Elewaut, D., Foeldvari, I., Gerloni, V., Rovensky, J., Minden, K., Vehe, R. K., Weiner, L. W., Horneff, G., Huppertz, H., Olson, N. Y., Medich, J. R., Carcereri-De-Prati, R., McIlraith, M. J., Giannini, E. H., Martini, A. 2008; 359 (8): 810-820

    Abstract

    Tumor necrosis factor (TNF) has a pathogenic role in juvenile rheumatoid arthritis. We evaluated the efficacy and safety of adalimumab, a fully human monoclonal anti-TNF antibody, in children with polyarticular-course juvenile rheumatoid arthritis.Patients 4 to 17 years of age with active juvenile rheumatoid arthritis who had previously received treatment with nonsteroidal antiinflammatory drugs underwent stratification according to methotrexate use and received 24 mg of adalimumab per square meter of body-surface area (maximum dose, 40 mg) subcutaneously every other week for 16 weeks. We randomly assigned patients with an American College of Rheumatology Pediatric 30% (ACR Pedi 30) response at week 16 to receive adalimumab or placebo in a double-blind fashion every other week for up to 32 weeks.Seventy-four percent of patients not receiving methotrexate (64 of 86) and 94% of those receiving methotrexate (80 of 85) had an ACR Pedi 30 response at week 16 and were eligible for double-blind treatment. Among patients not receiving methotrexate, disease flares (the primary outcome) occurred in 43% of those receiving adalimumab and 71% of those receiving placebo (P=0.03). Among patients receiving methotrexate, flares occurred in 37% of those receiving adalimumab and 65% of those receiving placebo (P=0.02). At 48 weeks, the percentages of patients treated with methotrexate who had ACR Pedi 30, 50, 70, or 90 responses were significantly greater for those receiving adalimumab than for those receiving placebo; the differences between patients not treated with methotrexate who received adalimumab and those who received placebo were not significant. Response rates were sustained after 104 weeks of treatment. Serious adverse events possibly related to adalimumab occurred in 14 patients.Adalimumab therapy seems to be an efficacious option for the treatment of children with juvenile rheumatoid arthritis. (ClinicalTrials.gov number, NCT00048542.)

    View details for Web of Science ID 000258568600006

    View details for PubMedID 18716298

  • Therapy Insight: cardiovascular disease in pediatric systemic lupus erythematosus NATURE CLINICAL PRACTICE RHEUMATOLOGY Sandborg, C., Ardoin, S. P., Schanberg, L. 2008; 4 (5): 258-265

    Abstract

    In 15-20% of cases, systemic lupus erythematosus (SLE) presents before the age of 18 years, and such early-onset SLE seems to be particularly severe. SLE is an independent risk factor for premature atherosclerosis and death in young, premenopausal women with SLE, even after controlling for traditional cardiovascular risk factors. Children and adolescents with SLE are particularly susceptible to this long-term threat to their cardiovascular health because they have an increased disease severity and a lengthy disease burden. Factors that contribute to premature atherosclerosis include the inflammatory and immune abnormalities that are intrinsic to SLE, primary dyslipidemias, and the secondary effects of treatments such as corticosteroids. However, few rheumatologists provide appropriate preventive or management strategies for the increased atherosclerosis risk in this age-group. Screening should be performed on a regular basis, including evaluation of, and counseling for, traditional risk factors. Studies of treatment in pediatric patients are limited, and treatment strategies are often extrapolated from adult studies. Statins hold promise because they have both lipid-lowering and anti-inflammatory effects. There have been few studies of the use of statins in adults or adolescents with SLE; however, trials are currently underway to address the safety and efficacy of statin use in pediatric SLE.

    View details for DOI 10.1038/ncprheum0789

    View details for Web of Science ID 000255348000009

    View details for PubMedID 18349862

  • Management of dyslipidemia in children and adolescents with systemic lupus erythematosus LUPUS Ardoin, S. P., Sandborg, C., Schanberg, L. E. 2007; 16 (8): 618-626

    Abstract

    Systemic lupus erythematosus (SLE) is an independent risk factor for atherosclerosis, placing children and adolescents with SLE at great risk for developing cardiovascular sequelae, including myocardial infarction, in adulthood. Dyslipidemia and other traditional cardiac risk factors occur frequently in pediatric SLE and are often under-recognized and under-treated. Two dyslipidemia patterns are evident in pediatric SLE. Active disease is characterized by elevated triglycerides (TG) and low high density lipoprotein (HDL). With SLE treatment HDL and TG often normalize, while total cholesterol and low density lipoprotein (LDL) rise. The complex pathophysiology of dyslipidemia in SLE involves cytokines, autoantibodies, disease activity, medications, diet, and physical activity level, as well as other factors. Routine screening for dyslipidemia with fasting lipid profiles is indicated for children and adolescents with SLE. If lipoprotein levels are abnormal, first line therapy involves diet and exercise interventions for a minimum of six months. For persistent dyslipidemia, several pharmacologic therapies are available. Hydroxychloroquine, a common treatment for SLE, can improve lipid profiles and should be considered for all patients with SLE. Statins and bile acid sequestrants are typically added first for dyslipidemia, while niacin and fibrates are reserved for refractory disease and optimally prescribed in a multidisciplinary lipid clinic. Future research is needed to further illuminate the mechanisms of dyslipidemia in pediatric SLE with well designed clinical trials to determine the safest and most effective interventions to correct lipid profiles and prevent atherosclerosis.

    View details for DOI 10.1177/0961203307079566

    View details for Web of Science ID 000249490500014

    View details for PubMedID 17711898

  • Availability of pediatric rheumatology training in United States pediatric residencies. Arthritis and rheumatism Mayer, M. L., Brogan, L., Sandborg, C. I. 2006; 55 (6): 836-842

    Abstract

    To characterize the availability of pediatric rheumatology training in general pediatric residencies.We surveyed 195 pediatric residency program directors in the US using a combined Web-based and paper-based survey format. The survey asked directors about the availability of an on-site pediatric rheumatologist in their institution, the availability of formal pediatric rheumatology rotations, and the types of physicians involved in teaching curriculum components related to pediatric rheumatology. Survey responses were analyzed using descriptive and bivariate statistics.Of the 195 program directors surveyed, 127 (65%) responded. More than 40% of responding programs did not have a pediatric rheumatologist on site. Programs with on-site pediatric rheumatologists were significantly more likely than those without on-site pediatric rheumatologists to have an on-site pediatric rheumatology rotation available (94% versus 9%; P < 0.001). Although pediatric rheumatologists' involvement in 4 curriculum areas relevant to pediatric rheumatology is nearly universal in programs with on-site pediatric rheumatologists, nearly two-thirds of programs without on-site pediatric rheumatologists rely on internist rheumatologists, general pediatricians, or other physicians to cover these areas.Programs without pediatric rheumatologists on site are less likely to have pediatric rheumatology rotations and are more likely to rely on internist rheumatologists and nonrheumatologists to address rheumatology-related curriculum components. Lack of exposure to pediatric rheumatology during residency may impede general pediatricians' ability to identify and treat children with rheumatic diseases, undermine resident interest in this field, and perpetuate low levels of supply.

    View details for PubMedID 17139658

  • Rafting the ethical rapids. HEC forum : an interdisciplinary journal on hospitals' ethical and legal issues Collier, J., Rorty, M., Sandborg, C. 2006; 18 (4): 332-341

    View details for PubMedID 17717757

  • Candidate early predictors for progression to joint damage in systemic juvenile idiopathic arthritis JOURNAL OF RHEUMATOLOGY Sandborg, C., Holmes, T. H., Lee, T., Biederman, K., Bloch, D. A., Emery, H., McCurdy, D., Mellins, E. D. 2006; 33 (11): 2322-2329

    Abstract

    To assess if joint damage at 2 years after diagnosis in patients with systemic juvenile idiopathic arthritis (SJIA) can be predicted by clinical or laboratory features assessed up to 3 or 6 months after diagnosis.Medical records from 70 children were retrospectively reviewed. The primary outcome measure was presence of joint damage at 2 years after diagnosis (JD2) as defined by presence of erosions or fusion in one or more joints. Potential predictor variables for JD2 in the first 3 and 6 months after diagnosis consisted of the highest observed white blood cell count, platelet count, erythrocyte sedimentation rate, active joint count, and presence of symptomatic pulmonary or cardiac disease or macrophage activation syndrome, and treatment data.The outcome of interest, JD2, was identified in 15/70 patients. Classification-tree analysis identified a pair of variables (highest observed platelet count and number of active joints) measured within the first 3 months after diagnosis that together predicted progression to JD2 with an estimated sensitivity of 87%, specificity of 82%, and positive predictive value of 57%. Multivariate logistic regression analyses at 3 months found that higher quantities of joints with active arthritis and early use of methotrexate (MTX) were factors significantly associated with increased odds of progression to JD2 (active joints odds ratio = 1.08, 95% CI 1.00-1.16, p = 0.04; MTX OR = 11.85, 95% CI 1.89-74.26, p = 0.01). Unsupervised cluster analysis identified 2 major phenotypes of patients at 3 months characterized by different ages at onset, acute phase markers, active joint counts, and presence of serositis. These phenotypes differed 3-fold in proportion of subjects progressing to JD2 (p < 0.05).By 3 months after diagnosis, a clinical phenotype based on active joint count and platelet count may be prognostic of an increased risk of progression to JD2. Use of corticosteroids did not appear to change the risk of joint damage. In contrast, the presence of serositis appeared to be associated with decreased risk of joint damage.

    View details for Web of Science ID 000242010700035

    View details for PubMedID 16960920

  • Systemic hyalinosis: A distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (ANTRX2) PEDIATRICS Shieh, J. T., Swidler, P., Martignetti, J. A., Ramirez, M. C., Balboni, I., Kaplan, J., Kennedy, J., Abdul-Rahman, O., Enns, G. M., Sandborg, C., Slavotinek, A., Hoyme, H. E. 2006; 118 (5): E1485-E1492

    Abstract

    We sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood.We report on 3 children who presented in infancy with symptoms and signs that initially were not recognized to be those of systemic hyalinosis. Although the children were evaluated for a variety of problems, including lysosomal storage disorders and nonaccidental trauma, all eventually underwent genetic analysis of the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic hyalinosis.We describe the recognizable but variable clinical phenotype of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals presented in early infancy with severe pain and progressive contractures. Initial diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case. Although 2 of the children died in infancy as a result of complications of chronic diarrhea, the third child has survived into midchildhood. These data suggest that some ANTRX2 mutations, such as that identified in the long-term survivor, may be associated with a less severe course of disease.Although some aspects of systemic hyalinosis may resemble lysosomal storage disorders, the clinical features of systemic hyalinosis are distinctive, and detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of affected individuals should allow for aggressive pain control and expectant management of the multiple associated problems, including gastrointestinal dysfunction.

    View details for DOI 10.1542/peds.2006-0824

    View details for Web of Science ID 000241731700101

    View details for PubMedID 17043134

  • Neuropsychiatric manifestations in pediatric systemic lupus erythematosus and association with antiphospholipid antibodies JOURNAL OF RHEUMATOLOGY Harel, L., Sandborg, C., Lee, T., von Scheven, E. 2006; 33 (9): 1873-1877

    Abstract

    To determine the prevalence of neuropsychiatric (NP) manifestations in children with systemic lupus erythematosus (SLE) using the 1999 American College of Rheumatology case definitions for NP syndromes in SLE, and their association with antiphospholipid antibodies (aPL).We performed a retrospective cohort study of 106 pediatric and adolescent SLE patients at 2 academic medical centers. Clinical and laboratory data were obtained by medical record review. All aPL testing was performed in standard clinical laboratories.Twenty-five patients (23.6%) had NP manifestations, including seizures (9.4%), headaches (4.7%), mood disorders (4.7%), cognitive dysfunction (4.7%), cerebrovascular accident (CVA), psychosis and pseudotumor (2.8% each), aseptic meningitis (0.9%), acute confusional state (0.9%), anxiety (0.9%), and cranial neuropathy (0.9%). NP events were not necessarily accompanied by an SLE flare. aPL were positive in 70% of all SLE patients, including anticardiolipin antibodies (aCL) in 64%, aCL IgG in 56%, aCL IgM in 35%, rapid plasma reagin or Venereal Disease Research Laboratory test in 13%, and lupus anticoagulant (LAC) in 18%. The only significant association between NP manifestations and aPL was for CVA and IgM aCL (p=0.03). LAC was slightly more common among patients with NP events, and the finding of LAC on more than one occasion was significantly associated with developing a NP event (p = 0.01).NP manifestations occur in about one-fourth of children with SLE, are an early event in the course of the disease, and are not necessarily accompanied by an SLE flare. Seizures are the most frequent symptom. Although aPL are common, their association with NP events, unlike in adults, is weak, except for CVA, suggesting a different pathogenic mechanism for NP manifestations in pediatric SLE.

    View details for Web of Science ID 000240377400030

    View details for PubMedID 16845706

  • The future of rheumatology research: the Childhood Arthritis and Rheumatology Research Alliance. Current problems in pediatric and adolescent health care Sandborg, C. 2006; 36 (3): 104-109

    View details for PubMedID 16473287

  • History of infection before the onset of juvenile dermatomyositis: Results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH Pachman, L. M., Lipton, R., Ramsey-Goldman, R., Shamiyeh, E., Abbott, K., Mendez, E. P., Dyer, A., McCurdy, D., Vogler, L., Reed, A., Cawkwell, G., Zemel, L., Sandborg, C., Rivas-Chacon, R., Hom, C., Ilowite, N., Gedalia, A., Gitlin, J., Borzy, M. 2005; 53 (2): 166-172

    Abstract

    To obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM).Parents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis.Children for which both a parent interview and physician medical records at diagnosis were available (n = 286) were included. Diagnoses were as follows: definite/probable JDM (n = 234, 82%), possible JDM (n = 43, 15%), or rash only (n = 9, 3%). The group was predominantly white (71%) and had a girl:boy ratio of 2:1. Although the mean age at onset was 6.7 years for girls and 7.3 years for boys, 25% of the children were < or =4 years old at disease onset. In the 3 months before onset, 57% of the children had respiratory complaints, 30% had gastrointestinal symptoms, and 63% of children with these symptoms of infection were given antibiotics.This study provides evidence that JDM affects young children. The symptoms of the typical rash and weakness often follow a history of respiratory or gastrointestinal complaints. These data suggest that the response to an infectious process may be implicated in JDM disease pathogenesis.

    View details for DOI 10.1002/art.21068

    View details for Web of Science ID 000228362800003

    View details for PubMedID 15818654

  • The first step: DNAR outside the hospital and the role of pediatric medical care providers AMERICAN JOURNAL OF BIOETHICS Collier, J., Sandborg, C. 2005; 5 (1): 85-86

    View details for DOI 10.1080/15265160590931197

    View details for Web of Science ID 000228667800029

    View details for PubMedID 16036677

  • Dyslipoproteinemia and premature atherosclerosis in pediatric systemic lupus erythematosus. Current rheumatology reports Schanberg, L. E., Sandborg, C. 2004; 6 (6): 425-433

    Abstract

    While modern treatments for systemic lupus erythematosus (SLE) have resulted in greatly improved long term outcome in children and adults, complications of atherosclerosis have become a major cause of morbidity and mortality. Although children and adolescents with SLE rarely experience adverse cardiovascular events before adulthood, dyslipoproteinemia and early evidence of premature atherosclerosis is present much earlier. Accelerated atherogenesis in SLE is multifactorial, most likely reflecting vascular, immune, and inflammatory changes along with medication effects. The long term complications of cardiovascular disease in childhood lupus present a particularly important target for intervention because of the potential return on investment by significantly lengthening life and improving quality of life over many decades. An ongoing multi-center, randomized, controlled trial, Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE), testing the efficacy of statins in preventing premature atherosclerosis in children and adolescents with SLE will guide future therapeutic intervention.

    View details for PubMedID 15527701

  • Adolescent rheumatology transitional care: steps to bringing health policy into practice RHEUMATOLOGY Chira, P., Sandborg, C. 2004; 43 (6): 687-689

    View details for DOI 10.1093/rheumatology/keh206

    View details for Web of Science ID 000221750700001

    View details for PubMedID 15126671

  • Frontal lobe seizures and uveitis associated with acute human parvovirus B19 infection JOURNAL OF CHILD NEUROLOGY Hsu, D., Sandborg, C., Hahn, J. S. 2004; 19 (4): 304-306

    Abstract

    We report a 5-year-old girl who developed repeated episodes of behavioral alterations shortly after human parvovirus B19 infection and uveitis. Video-electroencephalographic study demonstrated that these brief episodes were frontal lobe seizures. Seizures responded promptly to antiepilepsy medications. Further diagnostic testing did not reveal any rheumatologic disorders. Human parvovirus B19 infections in children are more commonly associated with febrile seizures and meningoencephalitis. Our case demonstrates that, rarely, it may be associated with the development of partial epilepsy.

    View details for Web of Science ID 000221419000013

    View details for PubMedID 15163099

  • Role of pediatric and internist rheumatologists in treating children with rheumatic diseases PEDIATRICS Mayer, M. L., Sandborg, C. I., Mellins, E. D. 2004; 113 (3): E173-E181

    Abstract

    To quantify and describe the role of internist and pediatric rheumatologists in the care of children with rheumatic diseases and identify factors associated with internist rheumatologists' willingness to treat children.We surveyed physician members of the American College of Rheumatology who currently practice in California (n = 589). Bivariate and logit analyses were used to examine the effects of training, provider, practice, and distance to the nearest pediatric rheumatologist on the likelihood that an internist rheumatologist treated children.Our effective response rate was 51%. More than one third of internist rheumatologists who practice in California reported treating pediatric patients. On average, internist rheumatologists who treated children saw 3.1 patients younger than 18 years weekly; half of these patients were 16 and 17 years of age. In logistic regression analysis, internist rheumatologists who treat pediatric patients were significantly more likely to practice in a multispecialty clinic (adjusted odds ratio: 3.5; 95% confidence interval: 1.9-9.7) and to live >50 miles from a pediatric rheumatologists (adjusted odds ratio: 6.8; 95% confidence interval: 2.1-22.7). In aggregate, we estimate that pediatric rheumatologists and internist rheumatologists provide care to 550 and 419 patients younger than 18 years per week, respectively.A substantial number of California internist rheumatologists are involved in the care of children, especially adolescents. The heavy involvement of internist rheumatologists in the care of children suggests that additional pediatric rheumatologists may be needed in select areas. Our findings have important implications for the size and distribution of the pediatric rheumatology workforce, the content of fellowship training for internist rheumatologists, and future studies of the relative quality of pediatric rheumatology care offered by internist rheumatologists. Furthermore, the role of internist subspecialists in caring for children with other chronic illness should be assessed.

    View details for Web of Science ID 000189344400048

    View details for PubMedID 14993573

  • Access to pediatric rheumatology care in the United States ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH Mayer, M. L., Mellins, E. D., Sandborg, C. I. 2003; 49 (6): 759-765

    Abstract

    To describe rheumatology providers, depict their availability, and determine the extent to which internist rheumatologists may expand access to care for children with rheumatic diseases.Using data from the American College of Rheumatology and the Bureau of Health Professions Area Resource File, we generated a national map of providers' practice locations and calculated distances between each county and the nearest rheumatologist. We also performed a logit analysis to identify provider and county characteristics that were associated with internist rheumatologists' willingness to treat children.Approximately 50% of the under 18 population in the United States live within 50 miles of a pediatric rheumatologist and nearly 90% live within 50 miles of a pediatric rheumatologist or an internist rheumatologist who treats children. Internist rheumatologists in private practice were 3 times as likely as those in medical schools to treat children (P < 0.001). Likewise, internist rheumatologists who live 200 or more miles from a pediatric rheumatologist were more than twice as likely to treat children as those who lived within 10 miles of a pediatric rheumatologist (P < 0.001).Our analysis suggests that internist rheumatologists are more geographically diffuse than pediatric rheumatologists and act as substitutes for pediatric rheumatologists in those regions that lack such providers. Research is needed to understand the role of internist rheumatologists in caring for children with rheumatic diseases and the quality of the care that they provide to this population.

    View details for DOI 10.1002/art.11462

    View details for Web of Science ID 000187232700004

    View details for PubMedID 14673961

  • Novel therapies in pediatric rheumatic diseases CURRENT OPINION IN PEDIATRICS Chira, P., Sandborg, C. I. 2003; 15 (6): 579-585

    Abstract

    Better understanding of the etiology of autoimmune diseases and their progression has brought about numerous novel therapies used in the treatment of pediatric rheumatic diseases. The introduction of biologic agents such as tumor necrosis factor inhibitors has changed how we approach and manage autoimmune diseases. This has led to a proliferation of other therapies targeting specific inflammatory processes evident in many rheumatic illnesses, with hopes of improving efficacy and decreasing adverse effects from treatment.Clinical studies demonstrate safety and efficacy of these newer medications in both adults and children. Although most of the novel therapies have been studied primarily in the adult rheumatic population, many are being evaluated in children in randomized controlled and open label trials as well. Long-term results are being collected regarding these newer regimens in both adults and children.This review looks at the risks and benefits of the variety of novel therapies including the new biologics, immunosuppressives, and stem cell transplantation currently being used in rheumatic conditions. Using these new therapies along with traditional antirheumatic medications, pediatric rheumatologists intervene to control disease early and more effectively to prevent long-term damage and complications.

    View details for Web of Science ID 000186887200007

    View details for PubMedID 14631203

  • Magnetic resonance imaging in the diagnosis and follow up of Takayasu's arteritis in children ANNALS OF THE RHEUMATIC DISEASES Aluquin, V. P., Albano, S. A., Chan, F., Sandborg, C., Pitlick, P. T. 2002; 61 (6): 526-529

    Abstract

    Takayasu's arteritis (TA) has a mortality rate of up to 40% in children. Because the clinical presentation of TA is often non-specific, accurate and prompt diagnosis depends on a high degree of awareness and appropriate laboratory and imaging studies.To examine the use of advanced magnetic resonance imaging (MRI) in evaluating, gauging activity, and following the complications of TA.T1 weighted, T2 weighted, contrast enhanced MR images, and MR angiograms of the chest and abdomen were obtained in three children (age range 11-14 years). The MRI studies confirmed the diagnosis of active TA and were repeated to evaluate response to treatment. Two patients showed complete resolution of lesions found on MRI at six and 12 months' follow up, while the third patient showed no significant improvement.MRI can be used to help establish the initial diagnosis of TA in children, and it can also be used to monitor disease activity and to guide treatment.

    View details for Web of Science ID 000175769200012

    View details for PubMedID 12006326

  • Expression of autoimmunity in the transition from childhood to adulthood: Role of cytokines and gender JOURNAL OF ADOLESCENT HEALTH Sandborg, C. 2002; 30 (4): 76-80

    View details for Web of Science ID 000174924300011

    View details for PubMedID 11943578

  • Type 1 diabetes mellitus and epilepsia partialis continua in a 6-year-old boy with elevated anti-GAD65 antibodies PEDIATRICS Olson, J. A., Olson, D. M., Sandborg, C., Alexander, S., Buckingham, B. 2002; 109 (3)

    Abstract

    A 6-year-old boy presented with epilepsia partialis continua 6 months after diagnosis of type 1 diabetes. Anti-glutamic acid decarboxylase 65 antibodies were found in his serum and cerebrospinal fluid. Anti-epileptic agents did not improve his seizures. High-dose steroids, plasmapheresis, and intravenous immunoglobulin resulted in decreased anti-glutamic acid decarboxylase 65 antibody levels and resolution of his seizures.

    View details for Web of Science ID 000174202800012

    View details for PubMedID 11875178

  • Systemic lupus erythematosus and antiphospholipid syndrome in children and adolescents CURRENT OPINION IN RHEUMATOLOGY Lee, T., von Scheven, E., Sandborg, C. 2001; 13 (5): 415-421

    Abstract

    Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) can be associated with significant morbidity in children and adolescents. Renal involvement in SLE appears to be more severe and more frequent in the pediatric age group, with the major predictors for poor outcome being the severity of histopathologic lesions, severity of renal impairment at diagnosis, and hypertension. In addition to currently recognized cardiovascular and pulmonary involvement, accelerated atherosclerosis is of increasing concern in young individuals with SLE, because of both disease effects and medication usage. Neuropsychiatric SLE seen in childhood ranges from subtle cognitive dysfunction to severe central nervous system involvement; however, there is controversy over the value of different diagnostic studies. APS in children may be associated with SLE, idiopathic, or associated with viral infections. Systemic anticoagulation is recommended for patients with thrombotic events, but long-term management has not been well studied in children.

    View details for Web of Science ID 000171262000013

    View details for PubMedID 11604598

  • Development of systemic lupus erythematosus following autologous bone marrow transplant for acute lymphocytic leukemia JOURNAL OF RHEUMATOLOGY Steinbach, W. J., Sandborg, C. I. 2001; 28 (6): 1467-1468

    View details for Web of Science ID 000169007900100

    View details for PubMedID 11409148

  • A randomized trial of methotrexate in newly diagnosed patients with type 1 diabetes mellitus CLINICAL IMMUNOLOGY Buckingham, B. A., Sandborg, C. I. 2000; 96 (2): 86-90

    Abstract

    The aim of this study was to determine whether low-dose, oral methotrexate therapy would prolong the remission phase at the onset of Type 1 diabetes. Ten newly diagnosed, nonacidotic, ICA-positive, Type 1 diabetics were randomly assigned to receive either methotrexate (5 mg/m(2)/week) or no immunosuppressive treatment. The study was not blinded and no placebo was given. Endogenous insulin production was assessed every 3 months by fasting and Sustacal-stimulated C-peptide levels. Methotrexate therapy was not beneficial in prolonging islet survival as assessed by fasting and stimulated C-peptide levels. Insulin requirements were generally lower in the control group, and islet failure, determined by an insulin requirement of >0.7 u/kg/day, occurred earlier for those receiving MTX (P < 0.02). Side effects of methotrexate treatment were minimal. There was no benefit from methotrexate therapy, and methotrexate therapy was associated with an earlier increase in insulin requirements.

    View details for DOI 10.1006/clim.2000.4882

    View details for Web of Science ID 000088615500003

    View details for PubMedID 10900154

  • Position statement of the American college of rheumatology regarding referral of children and adolescents to pediatric rheumatologists ARTHRITIS CARE AND RESEARCH Sandborg, C. I., Wallace, C. A. 1999; 12 (1): 48-51

    View details for Web of Science ID 000078495600008

    View details for PubMedID 10513490

  • Progressive multifocal leukoencephalopathy in a 15-year-old boy with scleroderma and secondary amyloidosis PEDIATRICS Hahn, J. S., Harris, B. T., Gutierrez, K., Sandborg, C. 1998; 102 (6): 1475-1479

    View details for Web of Science ID 000077311500033

    View details for PubMedID 9832587

  • Childhood systemic lupus erythematosus and neonatal lupus syndrome. Current opinion in rheumatology Sandborg, C. I. 1998; 10 (5): 481-487

    Abstract

    Systemic lupus erythematosus in children can present with a wide spectrum of disease manifestations. Significant organ system involvement appears to be more severe in children than in adults. Central nervous system disease continues to be difficult to diagnose because of the lack of sensitive and specific diagnostic tests. Renal function is the major determinant of long-term prognosis and management in children with lupus. Identification of patients who are most at risk for progression of renal disease and aggressive treatment, including corticosteroids and immunosuppressive agents, are indicated. Genetic susceptibility studies in lupus reveal multiple contributions from HLA and non-HLA genes. Current concepts regarding apoptosis and DNA-protein complexes and autoreactive T-cell help for anti-DNA antibody production suggest novel directions for therapies. New understandings of the pathogenesis of neonatal lupus syndrome and congenital heart block reveals important information about prospective monitoring and management of mothers and fetuses at risk.

    View details for PubMedID 9746865

  • Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus JOURNAL OF IMMUNOLOGY Berman, M. A., Sandborg, C. I., Wang, Z. S., Imfeld, K. L., Zaldivar, F., Dadufalza, V., Buckingham, B. A. 1996; 157 (10): 4690-4696

    Abstract

    IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). The mean IL-4 response of patients in the honeymoon stage was higher than the mean of the new onset patients, but significantly lower than the control group (p = 0.01). Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. IL-4 mRNA levels were measured using competitive reverse transcription PCR. The results showed greatly reduced mRNA levels in new onset IDDM. In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. The results suggest an imbalance of inflammatory vs anti-inflammatory cytokine production at the onset of IDDM. Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress.

    View details for Web of Science ID A1996VR79300053

    View details for PubMedID 8906850

  • IL-4 EXPRESSION IN HUMAN T-CELLS IS SELECTIVELY INHIBITED BY IL-1-ALPHA AND IL-1-BETA JOURNAL OF IMMUNOLOGY Sandborg, C. I., Imfeld, K. L., Zaldivar, F., Wang, Z. S., Buckingham, B. A., Berman, M. A. 1995; 155 (11): 5206-5212

    Abstract

    Imbalances in anti-inflammatory and proinflammatory cytokines may be responsible for initiation or progression of diverse pathologic states including autoimmune and infectious diseases. IL-4 production of proinflammatory cytokines and IL-12 promotes differentiation and activation of IFN-gamma-producing T cells, but does a counter-regulatory effect of proinflammatory cytokines on IL-4 production exist? This study evaluates the effect of proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-12, and TNF-alpha) on IL-4 production in primary human T cell cultures. PBMCs from healthy individuals were tested for IL-4 production in response to PHA and various cytokines. IL-4 was measured by proliferation of the IL-4-sensitive T cell line (CT.h4S) or ELISA. IL-1 alpha and IL-1 beta inhibited IL-4 production by 20 to 80% in > 92% of healthy individuals (p = 0.0001, paired t-test). IL-12 had an inhibitory effect on PBMC IL-4 production as previously described, but neither IL-6 nor TNF-alpha inhibited IL-4 production. IL-1 had no effect on PHA-induced PBMC or purified T cell proliferation or IL-2 production. IL-4 production by purified T cells stimulated by PHA or the combination of PMA with calcium ionophore (A23187) was inhibited by IL-1, and reconstitution with peripheral blood-derived adherent macrophages had no effect. IL-12 did not inhibit IL-4 production in stimulated purified T cells. Steady state IL-4 mRNA levels were determined by semiquantitative competitive reverse transcribed PCR (RT-PCR). Marked inhibition of IL-4 mRNA levels were seen at 5 h after exposure to IL-1. This interaction between IL-1 and IL-4 may be an important physiologic regulator of the balance between proinflammatory cytokines from activated macrophages and anti-inflammatory cytokines from T cells.

    View details for Web of Science ID A1995TF68600016

    View details for PubMedID 7594531

  • HIV TYPE-1 INDUCTION OF INTERLEUKIN-1 AND INTERLEUKIN-6 PRODUCTION BY HUMAN THYMIC CELLS AIDS RESEARCH AND HUMAN RETROVIRUSES Sandborg, C. I., Imfeld, K. L., Zaldivar, F., Berman, M. A. 1994; 10 (10): 1221-1229

    Abstract

    In vitro and in vivo studies have demonstrated that HIV can infect thymocytes at different maturational stages and lead to changes in the thymic microenvironment. To determine the effect of HIV on thymic stromal cells and the production of cytokines important in thymocyte development, three types of adherent thymic cultures were established and studied: thymic epithelial cells (TECs), macrophage-enriched, and mixed cultures of macrophages and TECs (M phi/TEC). Cultures were exposed to HIV-1 strains HIV-1IIIB and HIV-1Ba-L, and studied from day 2 to day 26 for the presence of infection, cytopathology, and cytokine (IL-1 alpha, IL-1 beta, and IL-6) production. M phi/TEC and macrophage-enriched cultures were infected by both HIV strains without cytopathic changes. The TECs grew well in culture for at least 6 weeks and showed no evidence of infection, cytopathology, or changes in cytokine production with HIV. Only cultures containing macrophages (M phi/TEC or macrophage enriched) showed changes in cytokine production with HIV. Sustained production of IL-1 alpha was seen for up to 20 days, with small or no increases in IL-1 beta. M phi/TEC cultures produced high constitutive levels of IL-6 that were not changed by HIV. Unstimulated macrophage-enriched cultures produced small amounts of IL-6 that were increased by HIV 20-fold. This study suggests that HIV infection in vivo can lead to infection of thymic macrophages resulting in cytokine abnormalities and a constant source for HIV to infect maturing thymocytes. These cytokine effects could lead to abnormal maturation and contribute to the lack of regeneration of the mature CD4+ T cell pool.

    View details for Web of Science ID A1994PP91000005

    View details for PubMedID 7848680

  • HIV-1 INFECTION OF MACROPHAGES PROMOTES LONG-TERM SURVIVAL AND SUSTAINED-RELEASE OF INTERLEUKIN-1-ALPHA AND INTERLEUKIN-6 AIDS RESEARCH AND HUMAN RETROVIRUSES Berman, M. A., Zaldivar, F., Imfeld, K. L., Kenney, J. S., Sandborg, C. I. 1994; 10 (5): 529-539

    Abstract

    HIV infection of macrophages in vivo may result in activation of monokine genes and cause persistent release of immunomodulatory and inflammatory cytokines. Studies that have examined cytokine (IL-1, IL-6, and TNF-alpha) activation by in vitro infection of normal peripheral blood mononuclear cells (PBMCs) with HIV-1 have produced conflicting results. The present study shows that for monokine induction by HIV-1-IIIB preparations derived from the H9 tumor cell line, partial purification of virus particles is essential. Infectious HIV-1 induces the release of high levels of IL-1 alpha, IL-1 beta, and IL-6 bioactivity by adherent PBMCs in the first 3 days following in vitro infection, but only IL-1 alpha and IL-6 continue to be released over several weeks of culture. High levels of bioactive IL-1 beta were released only up to 72 hr following infection, although intracellular IL-1 beta was detectable for at least 3 weeks. No TNF-alpha bioactivity or immunoreactive protein was detectable at > 48 hr in HIV-infected cultures. This time course of monokine release was dependent on the number of infectious particles added to PBMC cultures. In long-term cultures (> 1 month) HIV infection was found to promote the viability of macrophages. The finding of sustained release of IL-1 alpha and IL-6 by infected macrophages, without additional stimulation, suggests that these mediators are released by HIV-1-infected macrophages in AIDS patients, where they may interfere with proper immune regulation.

    View details for Web of Science ID A1994NR14600005

    View details for PubMedID 7917515

  • A NATURALLY-OCCURRING 6-9-KILODALTON INTERLEUKIN-1 (IL-1) INHIBITOR PREVENTS IL-1-MEDIATED ISLET CYTOTOXICITY BUT NOT IL-1-MEDIATED SUPPRESSION OF INSULIN-SECRETION JOURNAL OF IMMUNOTHERAPY KAWAHARA, D. J., Everts, M., Buckingham, B., Sandborg, C., Berman, M. 1991; 10 (3): 182-188

    Abstract

    Earlier studies have shown direct effects of interleukin-1 (IL-1) on isolated pancreatic islets. Coculture of isolated rat pancreatic islets with human rIL-1 beta for 6 days resulted in dose-dependent cytotoxicity (up to 100%) and suppression of insulin secretion (up to 88.5%). The cytotoxic effects of rIL-1 beta beta were blocked by the simultaneous presence of a naturally occurring 6-9-kilodalton (kDa) inhibitor of IL-1-induced T-cell proliferation. However, the ability of rIL-1 beta to suppress insulin secretion was not blocked by the 6-9-kDa inhibitor of IL-1 activity. This IL-1 inhibitor is produced by mononuclear cells and is resistant to pH 2, sensitive to heating at 56 degrees C for 30 min, has a pI of 4.5-5.6, and appears to be different from other recognized IL-1 inhibitors in both composition and mechanism of action. Unlike this IL-1 inhibitor, a monoclonal antibody specific for rIL-1 beta was able to neutralize both the islet cytotoxic and insulin modulatory effects of rIL-1 beta. These results demonstrate the use of an IL-1 inhibitor to prevent at least one mechanism of islet destruction, and suggest separate pathways for IL-1 mediated islet cytotoxicity and suppression of insulin secretion.

    View details for Web of Science ID A1991FM89500004

    View details for PubMedID 1868042

  • INTERLEUKIN-1 AND A 7-KDA T-CELL INHIBITORY MONOKINE REFLECT DISEASE-ACTIVITY IN INFECTION WITH HIV-1 JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY Sandborg, C. I., Berman, M. A., Imfeld, K. L., Cesario, T. C., Zaldivar, F. 1990; 3 (12): 1148-1154

    Abstract

    Previous studies demonstrated that cultured peripheral blood mononuclear cells (PBMC) from patients with AIDS produce high levels of interleukin 1 (IL-1) and a 7-kDa T-cell inhibitory monokine (TCIM). To determine if the increase in the production of these cytokines corresponded with disease activity, we studied the production of IL-1 and TCIM by PBMC from patients with different stages of human immunodeficiency virus (HIV) infection. Eight patients with asymptomatic seropositive infection, three patients with AIDS-related complex (ARC), three patients with persistent generalized lymphadenopathy (PGL), and six patients meeting the full criteria for diagnosis of AIDS were studied. Patients with AIDS produced increased amounts of TCIM (4.1 times control values, p less than 0.003) and IL-1 (2.0 times control values, p less than 0.05). In contrast, asymptomatic seropositive patients produced less TCIM (0.36 times control values, p less than 0.004) and IL-1 (0.61 times control values, p less than 0.05). Different trends in the levels of these factors produced by patients with ARC and PGL were noted, although results were not statistically significant in general. Patients with ARC tended to produce less IL-1 (0.42 times control values, p less than 0.05), whereas patients with PGL tended to produce increased amounts of IL-1 (1.7 times control values, NS). ARC patients produced a wide range of TCIM values (0.05-2.8 times control values, NS), and patients with PGL tended to produce increased TCIM values, (4.0 times control values, p less than 0.02). No correlations between the levels of IL-1 or TCIM and T-cell subpopulation numbers (CD4 or CD8) or CD4/CD8 ratios were found.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1990EK89100005

    View details for PubMedID 2123004

  • MODULATION OF IL-1-ALPHA, IL-1-BETA, AND 25K MR NON-IL-1 ACTIVITY RELEASED BY HUMAN MONONUCLEAR-CELLS JOURNAL OF LEUKOCYTE BIOLOGY Sandborg, C. I., Berman, M. A., Imfeld, K. L., Zaldivar, F., MASADA, M. P., Kenney, J. S. 1989; 46 (5): 417-427

    Abstract

    To determine if the release of IL-1 alpha and IL-1 beta by cultured PBMC could be independently modulated by different exogenous stimuli, we examined the effect of LPS, IFN gamma, latex beads, and indomethacin on the release of IL-1 alpha and IL-1 beta. PBMC culture supernatants were fractionated by Sephacryl-S-200 column chromatography or HPLC (TSK G3000SW), and each fraction was tested for thymocyte mitogenic activity in the presence or absence of preincubation with anti-IL-1 alpha or anti IL-1 beta monoclonal antibody (mAb) and for the presence of IL-1 alpha or IL-1 beta protein by ELISA. In all experiments, thymocyte mitogenic activity not neutralizable by anti-IL-1 alpha or anti-IL-1 beta mAb was detected in the 25K Mr range, which ranged from 12 to 50% of the total thymocyte mitogenic activity released, depending on the stimuli. Cultured PBMC from 95% of individuals release thymocyte mitogenic activity in the absence of exogenous stimuli, which was increased 1.3-to 7-fold by lopopolysaccharide (LPS) (25-50 micrograms/ml). All of this increased activity was due to increased release of IL-1 beta and non-IL-1 thymocyte mitogenic activity, with no change in the total amount of IL-1 alpha released. Indomethacin (0.1 microgram/ml) induced release of increased thymocyte mitogenic activity of 1.3- to 1.4-fold over unstimulated cultures. All of this increased activity was due to increased release of IL-1 alpha and non-IL-1 activity with a concomitant decrease in IL-1 beta release. Interferon gamma (40-100 U/ml) increased the amount of IL-1 alpha and decreased IL-1 beta and non-IL-1 activity released, resulting in no overall change in the total amount of thymocyte mitogenic activity. Molecular weight fractionation of the PBMC culture supernatants revealed that thymocyte mitogenic activity eluting in the 25K Mr range was not due to IL-1 alpha or IL-1 beta. With certain culture conditions, thymocyte mitogenic activity was detected in the 30-40K Mr range. PBMC cultured with LPS and latex beads in the absence of serum released 30-40K Mr IL-1 alpha, as well as 17K Mr IL-1 alpha and 17K Mr IL-1 beta. PBMC cultured in 2% fetal calf serum (FCS) alone from some donors released only 30-40K Mr thymocyte mitogenic activity. Both IL-1 alpha and IL-1 beta protein was detected by ELISA in this Mr range but only the IL-1 alpha was bioactive.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1989AX73400002

    View details for PubMedID 2509610

  • CHANGES IN CIRCULATING MONOCYTES IN PATIENTS WITH PROGRESSIVE SYSTEMIC-SCLEROSIS JOURNAL OF RHEUMATOLOGY Andrews, B. S., FRIOU, G. J., Berman, M. A., Sandborg, C. I., Mirick, G. R., Cesario, T. C. 1987; 14 (5): 930-935

    Abstract

    Circulating monocytes in 30 patients with progressive systemic sclerosis (PSS, scleroderma) and 28 age and sex matched normal controls were studied. Binding of the lectin peanut agglutinin (PA) was significantly reduced in PSS monocytes (p less than 0.001) together with a reduction in the density of nonspecific esterase staining (p less than 0.001) suggesting advanced maturation. Using monoclonal antibodies to identify cell surface markers, we demonstrated a significant reduction in PSS monocytes bearing the Leu M2 antigen (Mac 120, antigen presenting cells) over controls (p less than 0.05), but were unable to show any differences in the monocyte subpopulations using antisera against Leu M3 and HLA-DR surface antigens. The ectoenzymes 5'-nucleotidase (5'N) and alkaline phosphodiesterase 1 (APD1) were lower and leucine aminopeptidase (LAP) levels were higher in patients with PSS, compatible with immune activation. Interferon-gamma levels in serum did not appear to account for these changes, whereas the levels of Clq binding complexes correlated inversely with the levels of LAP (p less than 0.05). There was a strong correlation between the number of Leu M3 positive cells and the level of the ectoenzyme LAP (p less than 0.001). With increasing disease duration, higher levels of Clq binding complexes were detected (p less than 0.05). These results indicate that monocytes in PSS differ from those in normals and appear to have undergone advanced differentiation and activation changes.

    View details for Web of Science ID A1987K693100013

    View details for PubMedID 3501471

  • INTERLEUKIN-1 INHIBITOR MASKS HIGH INTERLEUKIN-1 PRODUCTION IN ACQUIRED-IMMUNODEFICIENCY-SYNDROME (AIDS) CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY Berman, M. A., Sandborg, C. I., CALABIA, B. S., Andrews, B. S., FRIOU, G. J. 1987; 42 (1): 133-140

    Abstract

    Monocyte functions, including interleukin 1 (IL-1) production, have been shown previously to be impaired in acquired immunodeficiency syndrome (AIDS). We have fractionated culture supernatants from unstimulated peripheral blood mononuclear cells (PBMCs) to determine whether the low IL-1 activity in AIDS was due to the presence of IL-1 inhibitors. The results demonstrate that PBMCs from patients with AIDS produce increased amounts of IL-1 activity compared with those of controls together with marked increases (10- to 20-fold) in the amounts of 50,000-100,000 and 6000-9000 molecular weight (MW) factors which inhibit IL-1 activity. These inhibitors mask IL-1 activity measured in the standard thymocyte proliferation assay for IL-1. The 6000-9000 MW IL-1 inhibitor shows the greatest increase in all AIDS patients (n = 5) compared with that of controls (n = 7). This inhibitor may block the IL-1 dependent maturation of T lymphocytes in AIDS and thereby contribute to the immunodeficiency.

    View details for Web of Science ID A1987F488600014

    View details for PubMedID 3491712

  • INCREASED PRODUCTION OF AN INTERLEUKIN-1 (IL-1) INHIBITOR WITH FIBROBLAST STIMULATING ACTIVITY BY MONONUCLEAR-CELLS FROM PATIENTS WITH SCLERODERMA CLINICAL AND EXPERIMENTAL IMMUNOLOGY Sandborg, C. I., Berman, M. A., Andrews, B. S., Mirick, G. R., FRIOU, G. J. 1986; 66 (2): 312-319

    Abstract

    We have previously demonstrated low IL-1 activity produced by peripheral blood mononuclear cells (PBMC) from patients with scleroderma (Sandborg et al., 1985) and the production of a 6-9 K IL-1 inhibitor by normal monocytes (Berman et al., 1986). To determine whether this inhibitor accounted for the low IL-1 activity present in scleroderma, the production of IL-1 and IL-1 inhibitor by PBMC from eight scleroderma patients was studied. Concentrated supernatants from 24 h cultures of unstimulated PBMC were fractionated on Sephacryl S-200 and tested for IL-1 and IL-1 inhibitor activity in the standard IL-1 thymocyte proliferation assay. In seven of eight patients, IL-1 inhibitor production was increased (average 3.3 X) compared to matched controls. IL-1 production was less than controls in six of eight patients. Partially purified preparations of the 6-9 K mol. wt IL-1 inhibitor were inhibitory to IL-1 induced thymocyte proliferation but stimulatory to fibroblast proliferation when purified by gel chromatography and chromatofocusing (pI 4.5-5.6). These data suggest that an IL-1 inhibitor with fibroblast stimulating activity is produced in higher amounts by PBMC from patients with scleroderma, and may contribute to the fibroblast proliferation and excessive collagen synthesis which is typical of this disease.

    View details for Web of Science ID A1986E801700008

    View details for PubMedID 3493098

  • SKIN, JOINT, AND PULMONARY CHANGES IN TYPE-I DIABETES-MELLITUS AMERICAN JOURNAL OF DISEASES OF CHILDREN Buckingham, B., PEREJDA, A. J., Sandborg, C., KERSHNAR, A. K., UITTO, J. 1986; 140 (5): 420-423

    Abstract

    Three hundred seventy-five patients with diabetes mellitus were examined for the presence of sclerodermalike skin changes, limited joint mobility, and vital capacity changes. Nineteen percent of patients had vital capacities 2 SDs below the mean of predicted values. There was no significant relationship between decreased vital capacities and duration of diabetes, sclerodermalike skin changes, limited joint mobility, smoking history, proteinuria, or retinopathy. Cutaneous involvement consisting of thickening, tightening, and/or a waxy quality of the skin was noted in 190 patients (51%). The severity of skin involvement correlated positively with the patients' duration of diabetes, age, severity of joint contractures, and diabetic retinopathy. Thus, sclerodermalike skin changes appear to reflect generalized connective tissue alterations in diabetes and may indicate increased risk for diabetic microvascular complications.

    View details for Web of Science ID A1986C085200017

    View details for PubMedID 3962933

  • LOSS OF EPIDERMAL LANGERHANS CELLS AND ENDOTHELIAL-CELL HLA-DR ANTIGENS IN THE SKIN IN PROGRESSIVE SYSTEMIC-SCLEROSIS JOURNAL OF RHEUMATOLOGY Andrews, B. S., FRIOU, G. J., Barr, R. J., Mirick, G. R., Berman, M., Sandborg, C., Ross, P. A. 1986; 13 (2): 341-348

    Abstract

    Skin biopsies from the volar aspect of the forearm were studied in 26 patients with progressive systemic sclerosis (PSS) (16 diffuse, 10 CREST) and 4 controls using monoclonal antibodies against Langerhans' cells, T lymphocytes, macrophages, B lymphocytes, NK/K cells and HLA-DR antigen(s). Langerhans' cells were reduced or absent (anti-T6, anti-HLA-DR) in 19 of 20 clinically involved and in all 6 uninvolved PSS skin biopsies. Electron microscopic studies of 3 PSS patients indicated a reduction in the number of Langerhans' cells, with normal morphology of the remaining. HLA-DR antigen(s) on dermal endothelial cells were absent or reduced in 8 of 20 involved and 5 of 6 uninvolved PSS skin biopsies, but were present on the surface of dermal mononuclear cells presumably representing activated T lymphocytes. Increased numbers of dermal macrophages were found in 19% of PSS biopsies compared with controls. Absence of Langerhans' cells appears to represent the most widespread immunopathological feature of PSS. It is also associated with absent endothelial HLA DR surface antigens and activated T lymphocytes within the dermis.

    View details for Web of Science ID A1986C612000022

    View details for PubMedID 2941574

  • STUDIES OF AN INTERLEUKIN-1 INHIBITOR - CHARACTERIZATION AND CLINICAL-SIGNIFICANCE CLINICAL AND EXPERIMENTAL IMMUNOLOGY Berman, M. A., Sandborg, C. I., CALABIA, B. S., Andrews, B. S., FRIOU, G. J. 1986; 64 (1): 136-145

    Abstract

    Supernatants from 24 h cultures of human peripheral blood mononuclear cells (PBMNC) were fractionated and tested for interleukin (IL-1) activity in the mouse thymocyte assay with phytohaemagglutinin (PHA). By the addition of individual supernatant fractions together with partially purified IL-1 to the thymocyte assay, we demonstrate the presence of strong inhibitory activity with a mol. wt of 5,000-9,000 and an isoelectric point of 4.5-5.6. The activity is both heat (56 degrees C) and acid (pH 1.5) resistant. This inhibitor has no detectable suppressive effect on optimal and suboptimal concanavalin A (Con A), pokeweed mitogen (PWM), and PHA responses of PBMNC. The action of the inhibitor appears to be specifically directed against IL-1 action on thymocytes and has no inhibitory effect on interleukin 2 (IL-2) activity. The findings show that adherent PBMNC produce both IL-1 and a factor which opposes IL-1 action on thymocytes but not on peripheral (mature) T cells. This factor may regulate T cell maturation, activation, and proliferation.

    View details for Web of Science ID A1986A802300020

    View details for PubMedID 3488147

  • INTERLEUKIN-1 PRODUCTION BY MONONUCLEAR-CELLS FROM PATIENTS WITH SCLERODERMA CLINICAL AND EXPERIMENTAL IMMUNOLOGY Sandborg, C. I., Berman, M. A., Andrews, B. S., FRIOU, G. J. 1985; 60 (2): 294-302

    Abstract

    Interleukin-1 (IL-1) production by peripheral blood mononuclear cells (PBMC) from patients with scleroderma and healthy controls was studied. Supernatants from unstimulated PBMC cultures from 10 of 13 patients with progressive systemic sclerosis (PSS) had significantly less IL-1 activity as measured by thymocyte proliferation than controls. IL-1 activity per monocyte/macrophage in both patients and controls was 10 times greater when PBMC were cultured at 10(5) cells/ml compared to 10(6) cells/ml. Five-fold dilution of supernatants from PBMC cultured at 10(6) cells/ml revealed more IL-1 activity than undiluted supernatant and addition of indomethacin increased IL-1 activity primarily of the undiluted supernatant. The results show that IL-1 activity from crude PBMC supernatants from PSS patients is low and may be regulated by non-dialysable inhibitors produced by PBMC and/or cell interactions.

    View details for Web of Science ID A1985AFY7200009

    View details for PubMedID 3874022

  • SCLERODERMA-LIKE CHANGES IN INSULIN-DEPENDENT DIABETES-MELLITUS - CLINICAL AND BIOCHEMICAL-STUDIES DIABETES CARE Buckingham, B. A., UITTO, J., Sandborg, C., Keens, T., Roe, T., Costin, G., KAUFMAN, F., Bernstein, B., Landing, B., Castellano, A. 1984; 7 (2): 163-169

    Abstract

    Children with insulin-dependent diabetes mellitus (IDDM) were examined for scleroderma-like changes of digital sclerosis and joint contractures. Of the 104 patients, 19 (18%) demonstrated these features; five patients had both multiple joint involvement and skin changes; three were studied in detail. All three had restrictive pulmonary disease. Histopathology of skin in these three patients demonstrated increased accumulation of collagen in the lower dermis. In two of the patients, the extractability of collagen in 0.5 N acetic acid was decreased by about 50% as compared with normal controls, which suggests increased cross-linkage of collagen. In addition, the mean nonenzymatic glycosylation of collagen in these three patients was 13 times that of controls. The results indicate that distinct histopathologic and biochemical changes can be detected in the skin of these patients. The results further support the hypothesis that nonenzymatic glycosylation may alter the turnover of collagen, thus contributing to the development of a scleroderma-like syndrome with skin, joint, and pulmonary findings in patients with IDDM.

    View details for Web of Science ID A1984SN20800012

    View details for PubMedID 6734383

  • NEONATAL HYPER-NATREMIA ASSOCIATED WITH ELEVATED SODIUM CONCENTRATION OF BREAST-MILK JOURNAL OF PEDIATRICS Anand, S. K., Sandborg, C., Robinson, R. G., Lieberman, E. 1980; 96 (1): 66-68

    View details for Web of Science ID A1980JB09500016

    View details for PubMedID 7350318

  • COMPETITION FOR HOST ESSENTIAL AND NONESSENTIAL FATTY-ACIDS BY EHRLICH ASCITES-CARCINOMA IN MICE CANCER RESEARCH Baker, N., Sandborg, C., Morris, D., Ookhtens, M. 1977; 37 (7): 2218-2225

    View details for Web of Science ID A1977DL36800043

    View details for PubMedID 861947

  • BLOOD-SAMPLING TECHNIQUES FOR STUDYING RAPIDLY TURNING OVER METABOLIC FUELS IN MICE LIPIDS Baker, N., Morris, D., Sandborg, C. 1976; 11 (11): 818-820

    Abstract

    Experiments were carried out in control and Ehrlich ascites carcinomatous mice to determine whether orbital venous sinus blood could be used to reflect blood in the systemic circulation (decapitation blood) in the case of a rapidly turning over metabolic fuel such as free fatty acids. The early time course of intravenously injected, labeled free fatty acids was measured using (9, 10-(3)H) palmitic acid and (1-(14)C) linoleate complexed to mouse serum. No significant differences between decapitation and orbital sinus blood were found at early times in either group of mice. The orbital sinus clearly contains blood that is not stagnant and is replaced so rapidly that it is suitable for studying very rapidly turning over, circulating metabolites.

    View details for Web of Science ID A1976CM57000008

    View details for PubMedID 994753

Conference Proceedings


  • The Childhood Arthritis & Rheumatology Research Alliance Network Registry: Demographics and Characteristics of the Initial One Year Cohort Natter, M. D., Winsor, J. R., Fox, K. A., Ilowite, N. T., Mandl, K. D., Mieszkalski, K. L., Sandborg, C. I., Sundy, J. S., Wallace, C. A., Schanberg, L. E. WILEY-BLACKWELL. 2011: S291-S292
  • Consensus development of a corticosteroid (CS) tapering algorithm for the randomized placebo phase study of rilonocept in the treatment of systemic JIA (RAPPORT) Sandborg, C., Giannini, E. H., Feldman, B. M., GOTTLIEB, B., Grom, A., Hashkes, P., Imundo, L., Kimura, Y., Lang, B., Miller, M. L., Milojevic, D., O'Neil, K., Punaro, M., Ruth, N., Schanberg, L. E., Singer, N., Vehe, R., Verbsky, J., Wallace, C., Woodward, C., Zemel, L., Kenney, K., Rivera, M., Ilowite, N. WILEY-BLACKWELL. 2008: S248-S249
  • Clinical laboratory markers of cardiovascular risk in a pediatric SLE cohort Ardoin, S., Schanberg, L., Bamhart, H., Yow, E., Mieszkalski, K., von Scheven, E., Ilowite, N., Eberhard, A., Levy, D., Kimura, Y., Silverman, E., Bowyer, S., Punaro, M., Singer, N., Sherry, D., Silver, R., McCurdy, D., Klein-Gitelman, M., Wallace, C., Wagner-Weiner, L., Higgins, G., Brunner, H., Jung, L., Jennifer, S. A., Sandborg, C. WILEY-BLACKWELL. 2008: S252-S253
  • Reduced levels of FasL and apoptosis resistance in SJIA monocytes Srivastava, S., Macaubas, C., Lee, T., Sandborg, C., Mellins, E. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2008: S93-S93
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