Mark V. Rubertone

Bio: Mark V. Rubertone is an academic researcher from United States Department of the Army. The author has contributed to research in topics: Risk factor & Seminoma. The author has an hindex of 23, co-authored 40 publications receiving 4219 citations. Previous affiliations of Mark V. Rubertone include University of Southern California & Walter Reed Army Institute of Research.

Development of autoantibodies before the clinical onset of systemic lupus erythematosus.

Abstract: Background Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis. Methods The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls. Results In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti–double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 pe...

Temporal Relationship Between Elevation of Epstein-Barr Virus Antibody Titers and Initial Onset of Neurological Symptoms in Multiple Sclerosis

Abstract: Context Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. Objective To determine whether antibodies to EBV are elevated before the onset of MS. Design, Setting, and Participants Nested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n=83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Serial samples collected before the onset of symptoms were available for 69 matched case-control sets. Main Outcome Measures Antibodies including IgA against EBV viral capsid antigen (VCA), and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. Results The average time between blood collection and MS onset was 4 years (range, 1-11 years). The strongest predictors of MS were serum levels of IgG antibodies to EBNA complex or EBNA-1. Among individuals who developed MS, serum antibody titers to EBNA complex were similar to those of controls before the age of 20 years (geometric mean titers: cases=245, controls=265), but 2- to 3-fold higher at age 25 years and older (cases=684, controls=282; P.001). The risk of MS increased with these antibody titers; the relative risk (RR) in persons with EBNA complex titers of at least 1280 compared with those with titers less than 80 was 9.4 (95% confidence interval [CI], 2.5-35.4; P for trend .001). In longitudinal analyses, a 4-fold increase in anti-EBNA complex or anti–EBNA-1 titers during the follow-up was associated with a 3-fold increase in MS risk (EBNA complex: RR,3.0; 95% CI, 1.36.5; EBNA-1: RR, 3.0; 95% CI, 1.2-7.3). No association was found between cytomegalovirus antibodies and MS. Conclusion These results suggest an age-dependent relationship between EBV infection and development of MS.

The Defense Medical Surveillance System and the Department of Defense serum repository: glimpses of the future of public health surveillance.

Abstract: The Defense Medical Surveillance System (DMSS) is the central repository of medical surveillance data for the US armed forces. The DMSS integrates data from sources worldwide in a continuouslyexpanding relational database that documents the military and medical experiences of servicemembers throughout their careers. The Department of Defense Serum Repository (DoDSR) is a central archive of sera drawn from servicemembers for medical surveillance purposes. Currently, the DMSS contains data relevant to more than 7 million individuals who have served in the armed forces since 1990, and the DoDSR contains more than 27 million specimens that are linkable to data in the DMSS. Recent applications of the DMSS and DoDSR provide glimpses of the capabilities and uses of comprehensive public health surveillance systems.

Persistent Organochlorine Pesticides and Risk of Testicular Germ Cell Tumors

Abstract: BACKGROUND Exposure to endocrine-disrupting chemicals, such as persistent organochlorine pesticides, has been suggested to increase the risk of testicular germ cell tumors (TGCTs). METHODS To study the relationship of POP exposure to TGCT risk, prediagnostic serum samples from 754 case subjects and 928 control subjects enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study were analyzed for cis-nonachlor, trans-nonachlor, oxychlordane, total chlordanes, beta-hexachlorocyclohexane, mirex, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyltrichloroethane. Adjusted odds ratios (ORs) and their associated 95% confidence intervals (CIs) for the risk of TGCT overall and for the histological subgroups, seminoma and nonseminoma, were estimated using multivariable logistic regression. All statistical tests were two-sided. RESULTS TGCT risk was statistically significantly associated with higher plasma levels of p,p'-DDE (for highest quartile [Q4] vs lowest quartile [Q1], OR = 1.71, 95% CI = 1.23 to 2.38, P(trend) = .0002) and of two chlordane components, cis-nonachlor (Q4 vs Q1, OR = 1.56, 95% CI = 1.11 to 2.18, P(trend) = .009) and trans-nonachlor (Q4 vs Q1, OR = 1.46, 95% CI = 1.07 to 2.00, P(trend) = .026). Seminoma risk was statistically significantly associated with p,p'-DDE (Q4 vs Q1, OR = 1.91, 95% CI = 1.22 to 2.99, P(trend) = .0008), cis-nonachlor (Q4 vs Q1, OR = 1.93, 95% CI = 1.27 to 2.93, P(trend) = .0045), trans-nonachlor (Q4 vs Q1, OR = 1.72, 95% CI = 1.11 to 2.67, P(trend) = .033), and a chlordane metabolite, oxychlordane (Q4 vs Q1, OR = 1.64, 95% CI = 1.04 to 2.60, P(trend) = .048), whereas nonseminoma risk showed a statistically significant association with p,p'-DDE only (Q4 vs Q1, OR = 1.63, 95% CI = 1.10 to 2.42, P(trend) = .0044). CONCLUSIONS Increased exposure to p,p'-DDE may be associated with the risk of both seminomatous and nonseminomatous TGCTs, whereas exposure to chlordane compounds and metabolites may be associated with the risk of seminoma. Because evidence suggests that TGCT is initiated in very early life, it is possible that exposure to these persistent organic pesticides during fetal life or via breast feeding may increase the risk of TGCT in young men.

Multiple sclerosis and Epstein-Barr virus.

Abstract: ContextInfection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear.ObjectiveTo determine whether antibodies to EBV are elevated before the onset of MS.Design, Setting, and PopulationNested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n = 83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected.Main Outcome MeasuresAntibodies including IgA against EBV viral capsid antigen (VCA) and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus.ResultsThe average time between blood collection and MS onset was 4 years. The strongest predictors of MS were serum levels of IgG antibodies to VCA or EBNA complex. The risk of MS increased monotonically with these antibody titers; relative risk (RR) in persons in the highest category of VCA (≥2560) compared with those in the lowest (≤160) was 19.7 (95% confidence interval [CI], 2.2-174; P for trend = .004). For EBNA complex titers, the RR for those in the highest category (≥1280) was 33.9 (95% CI, 4.1-283; P for trend <.001) vs those in the lowest category (≤40). Similarly strong positive associations between EBV antibodies and risk of MS were already present in samples collected 5 or more years before MS onset. No association was found between cytomegalovirus antibodies and MS.ConclusionThese results suggest a relationship between EBV infection and development of MS.

Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care.

Abstract: background The current combat operations in Iraq and Afghanistan have involved U.S. military personnel in major ground combat and hazardous security duty. Studies are needed to systematically assess the mental health of members of the armed services who have participated in these operations and to inform policy with regard to the optimal delivery of mental health care to returning veterans. methods We studied members of four U.S. combat infantry units (three Army units and one Marine Corps unit) using an anonymous survey that was administered to the subjects either before their deployment to Iraq (n=2530) or three to four months after their return from combat duty in Iraq or Afghanistan (n=3671). The outcomes included major depression, generalized anxiety, and post-traumatic stress disorder (PTSD), which were evaluated on the basis of standardized, self-administered screening instruments. results Exposure to combat was significantly greater among those who were deployed to Iraq than among those deployed to Afghanistan. The percentage of study subjects whose responses met the screening criteria for major depression, generalized anxiety, or PTSD was significantly higher after duty in Iraq (15.6 to 17.1 percent) than after duty in Afghanistan (11.2 percent) or before deployment to Iraq (9.3 percent); the largest difference was in the rate of PTSD. Of those whose responses were positive for a mental disorder, only 23 to 40 percent sought mental health care. Those whose responses were positive for a mental disorder were twice as likely as those whose responses were negative to report concern about possible stigmatization and other barriers to seeking mental health care. conclusions This study provides an initial look at the mental health of members of the Army and the Marine Corps who were involved in combat operations in Iraq and Afghanistan. Our findings indicate that among the study groups there was a significant risk of mental health problems and that the subjects reported important barriers to receiving mental health services, particularly the perception of stigma among those most in need of such care.

Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology

Abstract: The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Development of autoantibodies before the clinical onset of systemic lupus erythematosus.

Abstract: Background Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis. Methods The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls. Results In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti–double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 pe...