Biomedical subjects

Mark V Rubertone

Publications and source records attributed to Mark V Rubertone.

12 recordsLinked to original sources

PubMed2007

A case-control investigation of immune function gene polymorphisms and risk of testicular germ cell tumors.

There is reason to suspect that testicular germ cell tumor (TGCT) development may be influenced by cytokines, secreted proteins that modulate tumor immune surveillance activity as well as a variety of processes in the testis. To address this hypothesis, we conducted a case-control analysis (508 cases, 608 controls) of 32 putatively functional single-nucleotide polymorphisms (SNP) in 16 immune function genes among non-Hispanic Caucasian participants in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study. The TGFB1 Ex5-73C>T variant was positively associated with TGCT (CT/TT versus CC: odds ratio, 1.73; 95% confidence interval, 1.01-2.95; P(trend) = 0.05); additionally, haplotypes of the assessed TGFB1 SNPs (-509C>T, 327C>T, Ex1-282C>G, and Ex5-73C>T) differed in frequency between cases and controls (all TGCT, P 0.07; seminoma, P 0.04; nonseminoma, P 0.11). We also observed excess frequencies among TGCT cases versus controls of LTA 252G (P(trend) = 0.08) and of the TNF variants -1042C (P(trend) = 0.06), -1036T (P(trend) = 0.07), and -238G (P(trend) = 0.09). Analyses of haplotypes for LTA-TNF SNPs (LTA -91C>A, LTA 252A>G, TNF -863C>A, TNF -857C>T, TNF -308G>A, and -238G>A) were similarly suggestive of an association with TGCT (P = 0.06) and nonseminoma (P = 0.04), but not seminoma (P = 0.21). Polymorphisms in other genes were found to be associated only with seminoma (IL2) or nonseminoma (IFNGR2 and IL10). However, none of the associations remained noteworthy after applying the false discovery rate method to control for multiple testing. In conclusion, our findings suggest that polymorphisms in TGFB1 and LTA/TNF, and possibly other immune function genes, may influence susceptibility to TGCT.

Case-Control Studies↗

PubMed2006

Body size, dairy consumption, puberty, and risk of testicular germ cell tumors.

The etiology of testicular germ cell tumors (TGCTs) is poorly understood, with cryptorchidism and family history being the only well-established risk factors. Body size, age at puberty, and dairy consumption, however, have been suggested to be related to TGCTs. To clarify the relation of these variables to TGCT risk and to one another, the authors analyzed data from 767 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study (2002-2005). Overall, increased height was significantly related to risk (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.36, 2.45), though body mass index was not (OR = 1.06, 95% CI: 0.66, 1.69). There was no association with age at puberty, based on ages at first shaving (OR = 1.29, 95% CI: 0.96, 1.73), voice changing (OR = 0.97, 95% CI: 0.71, 1.32), and nocturnal emissions (OR = 1.00, 95% CI: 0.73, 1.37). Similarly, there was no relation with dairy consumption at any age between birth and 12th grade. These results suggest that height is a risk factor for TGCTs, but the relation is unlikely explained by childhood dairy consumption. As adult height is largely determined in the first 2 years of life, increased attention to events in this interval may help elucidate the etiology of TGCTs.

Adult↗

PubMed2006

Maternal smoking and testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a non-parent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, non-seminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons.

Adolescent↗

PubMed2006

Comparing the population health impacts of medical conditions using routinely collected health care utilization data: nature and sources of variability.

Prevention activities are designed and resourced based on perceptions of the relative population health impacts of various conditions. We examined the nature and variability of rankings of "conditions" based on how they are defined and how their population health impacts are measured. The first listed diagnosis from all hospitalizations and ambulatory visits of U.S. service members during 2002 was used to rank conditions (as defined by two standard classification systems) using five different measures of population health impacts. Less than 10% of all conditions accounted for more than one-half of total population health impact, regardless of how conditions were defined or impacts measured. However, specific conditions with the largest impacts varied depending on the classification system and impact measure. Four groups of related conditions--acute musculoskeletal injuries, pregnancy-related conditions, respiratory infections, and mental disorders (including substance abuse)--accounted for disproportionately large impacts regardless of the measure. The identification of conditions with the largest population health impacts depends on the nature and degree of aggregation in defining conditions and the measure of impact. The findings are relevant to prevention planning and resourcing.

Acute Disease↗

PubMed2005

Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis.

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, 1.3-6.5; 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.

Adult↗

PubMed2004

The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus.

OBJECTIVE: To determine whether antiphospholipid antibodies (aPL) occur before the diagnosis of systemic lupus erythematosus (SLE) and before initial clotting events, and whether their presence early in the disease course influences clinical outcome. METHODS: Serum samples obtained from 130 lupus patients before and after SLE diagnosis were screened for IgG and IgM aPL using an anticardiolipin (aCL) enzyme-linked immunosorbent assay. Medical records of all patients were carefully reviewed for data on the time of onset of SLE features meeting clinical criteria and on disease manifestations. RESULTS: Twenty-four patients (18.5%) were positive for IgG and/or IgM aCL prior to SLE diagnosis. Anticardiolipin antibodies appeared from 7.6 years prior to SLE diagnosis to within the same month as SLE diagnosis, with a mean onset occurring 3.0 years before SLE diagnosis. Additionally, aCL presence early in the disease process seemed to predict a more severe clinical outcome; these patients eventually met an average of 6.1 of the 11 classification criteria for SLE, compared with 4.9 criteria for other patients (P < 0.001). The early aCL-positive population also had more frequent renal disease, central nervous system disease, thrombocytopenia, and clotting events. In this population, aCL preceded initial thrombotic events by a mean of 3.1 years. CONCLUSION: Anticardiolipin antibodies in SLE patients tend to precede initial clotting events by several years. Furthermore, the presence of early, prediagnosis aPL seems to herald a more varied, severe clinical course with earlier onset in patients with SLE.

Adolescent↗

PubMed2003

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

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 percent, anti-nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti-nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti-double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti-nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies. CONCLUSIONS: Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.

Antibodies, Antinuclear↗

PubMed2003

Comprehensive systematic surveillance for adverse effects of anthrax vaccine adsorbed, US Armed Forces, 1998-2000.

Routine vaccinations of US military personnel with Anthrax Vaccine Adsorbed began in 1998. To systematically identify clinical diagnoses reported more frequently after vaccination than before, all military personnel were retrospectively assigned to pre- or post-vaccination cohorts. Cohort assignments were based on vaccination statuses each day of the 3-year surveillance period. For each cohort, rates of hospitalizations and ambulatory visits for 843 specific diagnoses were calculated using data in a public health surveillance system. Compared to the pre-vaccination cohort, the post-vaccination cohort had statistically higher rates of hospitalizations for 17 diagnoses, of ambulatory visits for 34 diagnoses, and in both clinical settings for one diagnosis (malaria). After accounting for systematic differences in coding/reporting and residual confounding, the number and nature of clinical diagnoses more frequent after anthrax vaccination than before were consistent with expectations due to random variation. This surveillance suggests that Anthrax Vaccine Adsorbed has few, if any, clinically significant adverse effects.

Adolescent↗

PubMed2003

Multiple sclerosis and Epstein-Barr virus.

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 POPULATION: 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. 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. 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 (> or =2560) compared with those in the lowest (< or =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 (> or =1280) was 33.9 (95% CI, 4.1-283; P for trend <.001) vs those in the lowest category (< or =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. CONCLUSION: These results suggest a relationship between EBV infection and development of MS.

Adolescent↗

PubMed2003

Analysis of adverse events after anthrax immunization in US Army medical personnel.

A broad range of health effects in a cohort of 601 health care personnel, immunized with anthrax vaccine adsorbed (AVA) as a military occupational health requirement, were assessed to evaluate adverse events both qualitatively and quantitatively. Active surveillance showed that localized reactions were common and occurred more often in women than men. Five patients were reported to the Vaccine Adverse Event Reporting System, but only one event could be definitively attributed to immunization, a large localized reaction. Two separate cohort studies, one using nested data from a standardized health risk appraisal instrument and the other comparing rates of outpatient visits and hospitalizations, did not reveal significant differences between AVA-immunized and unimmunized individuals. Our findings suggest that AVA is relatively reactogenic but do not indicate serious adverse health effects due to immunization.

Adult↗

PubMed2003

Timing and completeness of routine testing for antibodies to human immunodeficiency virus type 1 among active duty members of the U.S. Armed Forces.

Since 1985, the U.S. Armed Forces have conducted routine testing of personnel for antibodies to human immunodeficiency virus type 1. Sera that remain after testing are archived in the Department of Defense serum repository for potential uses in medical surveillance, clinical, and research activities. The goal of this study was to document the timing and completeness of routine human immunodeficiency virus type 1 testing among active duty military personnel and to identify factors associated with more recent testing. Demographic characteristics for active duty personnel were obtained from the Defense Medical Surveillance System. Of all individuals on active duty on August 31, 2001 (N = 1,370,367), 98.6% had been tested. Older personnel, those with postgraduate degrees, and married personnel had the longest time intervals since their most recent tests. The results of this analysis may inform the planning and conduct of human immunodeficiency virus type 1 prevention programs as well as deployment-related or other surveillance activities.

AIDS Serodiagnosis↗

PubMed2002

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

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 continuously expanding relational database that documents the military and medical experiences of service members throughout their careers. The Department of Defense Serum Repository (DoDSR) is a central archive of sera drawn from service members 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.

Confidentiality↗