99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: Epstein-Barr virus and multiple sclerosis: epidemiological evidence.

While the causes of multiple sclerosis (MS) are unknown, there is strong evidence that infection with Epstein-Barr virus (EBV) is an important factor. In this review, we discuss the epidemiological evidence and argue for a causal role of EBV in MS aetiology. One of the most striking and consistent observations is that MS is extremely rare among EBV-negative individuals.

Combined effects of smoking, anti-EBNA antibodies, and HLA-DRB1*1501 on multiple sclerosis risk.

Objective: To examine the interplay between smoking, serum antibody titers to the Epstein-Barr virus nuclear antigens (anti-EBNA), and HLA-DR15 on multiple sclerosis (MS) risk.

Methods: Individual and pooled analyses were conducted among 442 cases and 865 controls from 3 MS case-control studies-a nested case-control study in the Nurses' Health Study/Nurses' Health Study II, the Tasmanian MS Study, and a Swedish MS Study. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for the association between smoking, anti-EBNA titers, HLA-DR15, and MS risk.

Epstein-barr virus infection and multiple sclerosis: a review.

Epstein-Barr virus (EBV) infection results in a life-long persistence of the virus in the host's B-lymphocytes and has been associated with numerous cancers including Burkitt's lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. There is considerable evidence that EBV infection is a strong risk factor for the development of multiple sclerosis. Early age at primary EBV infection is typically asymptomatic, but primary infection during adolescence or adulthood often manifests as infectious mononucleosis, which has been associated with a two- to threefold increased risk of MS.

Alcohol intake and risk of coronary heart disease in younger, middle-aged, and older adults.

Background: Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men <40 years of age and in women <50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults.

Persistent organochlorine pesticides in serum and risk of Parkinson disease.

Background: Pesticides have been implicated as likely environmental risk factors for Parkinson disease (PD), but assessment of past exposure to pesticides can be difficult. No prior studies of pesticide exposure and PD used biomarkers of exposure collected before the onset of PD. Our investigation examined the association between prospective serum biomarkers of organochlorine pesticides and PD.

Diethylstilbestrol exposure in utero and depression in women.

Diethylstilbestrol (DES) is an estrogenic endocrine disruptor with long-term health effects, possibly including depression, following exposure in utero. Understanding the relation between in utero DES exposure and depression will provide insight to the potential adverse effects of bisphenol A, a functionally similar and ubiquitous endocrine disruptor. The association between in utero DES exposure and depression was assessed among participants in the Nurses' Health Study II who first reported their history of antidepressant use in 1993 and lifetime history of depressive symptoms in 2001.

Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson's disease in men and women.

Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. In a nested case-control study within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we examined associations between single nucleotide polymorphisms (SNPs) of caffeine metabolizing genes (CYP1A2 and NAT2) and estrogen receptors (ESR1 and ESR2), their interaction with caffeine intake and hormone replacement therapy (PMH) use (collected prospectively) and risk of PD. We matched 159 female cases to 724 controls and 139 male cases to 561 controls on birth year, source of DNA (blood or buccal smear), age and sex.

Restless legs syndrome and erectile dysfunction.

Study Objectives: Dopaminergic hypofunction in the central nervous system may contribute to restless legs syndrome (RLS) and erectile dysfunction (ED). We therefore examined whether men with RLS have higher prevalences of ED.

Design: RLS was assessed using a set of standardized questions.

Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis.

The extent to which potential genetic determinants of vitamin D levels may be related to multiple sclerosis (MS) risk has not been thoroughly explored. The objective of this study was to determine whether polymorphisms in VDR, CYP27B1, CYP24A1, CYP2R1 and DBP are associated with the risk of MS and whether these variants may modify associations between environmental or dietary vitamin D on MS risk. A nested case-control study was conducted in two, large cohorts of US nurses, including 214 MS cases and 428 age-matched controls.

Body size and risk of MS in two cohorts of US women.

Objective: To examine whether obesity during childhood, adolescence, or adulthood is associated with an increased risk of multiple sclerosis (MS).

Methods: Women in the Nurses' Health Study (n = 121,700) and Nurses' Health Study II (n = 116,671) provided information on weight at age 18 and weight and height at baseline, from which body mass index was derived. Women also selected silhouettes representing their body size at ages 5, 10, and 20.

Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score.

Background: Prediction of susceptibility to multiple sclerosis (MS) might have important clinical applications, either as part of a diagnostic algorithm or as a means to identify high-risk individuals for prospective studies. We investigated the usefulness of an aggregate measure of risk of MS that is based on genetic susceptibility loci. We also assessed the added effect of environmental risk factors that are associated with susceptibility for MS.

Family history of melanoma and Parkinson disease risk.

Background: Co-occurrence of Parkinson disease (PD) and melanoma has been reported in numerous studies. If this was due to common genetic mechanisms, a positive family history of melanoma would be associated with an excessive PD risk, independent of environmental risk factors for PD.

Methods: We prospectively examined associations between a family history of melanoma and PD among 157,036 men and women free of PD at baseline (1990 for men and 1982 for women) who participated in 2 ongoing US cohorts: the Health Professional Follow-up Study and the Nurses' Health Study.

Urate as a predictor of the rate of clinical decline in Parkinson disease.

Background: The risk of Parkinson disease (PD) and its rate of progression may decline with increasing concentration of blood urate, a major antioxidant.

Objective: To determine whether serum and cerebrospinal fluid concentrations of urate predict clinical progression in patients with PD.

Design, Setting, And Participants: Eight hundred subjects with early PD enrolled in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial.

Smoking and disease progression in multiple sclerosis.

Background: Although cigarette smokers are at increased risk of developing multiple sclerosis (MS), the effect of smoking on the progression of MS remains uncertain.

Objective: To establish the relationship between cigarette smoking and progression of MS using clinical and magnetic resonance imaging outcomes

Design: Cross-sectional survey and longitudinal follow-up for a mean of 3.29 years, ending January 15, 2008.

Serum uric acid and risk of multiple sclerosis.

Because of evidence implicating oxidative stress in multiple sclerosis pathogenesis, it has been postulated that high levels of urate, a potent antioxidant, could reduce risk or favorably influence disease progression. We conducted a prospective study to determine whether serum urate levels contribute to prediction of multiple sclerosis risk. Analyses included 31 cases with blood collected a median of 1.

Reproductive factors, exogenous estrogen use, and risk of Parkinson's disease.

To determine if reproductive factors or exogenous estrogen are associated with risk of Parkinson's disease (PD), we conducted a prospective study with 22 years of follow-up among postmenopausal participants in the Nurses' Health Study. Relative risks (RRs) and 95% confidence intervals (CIs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. Risk of PD was not significantly associated with any of the reproductive factors measured or exogenous estrogen use.

The relationship between handedness and risk of multiple sclerosis.

Background: Left-handedness has been studied as a marker for in-utero exposure to sex steroid hormones, and an increased risk of autoimmune and immune disorders among left-handed individuals has been suggested.

Objective: This study examines the relationship between hand preference and risk of multiple sclerosis, a presumed autoimmune disorder of unknown etiology.

Methods: The study population comprised participants in the Nurses' Health Study, an ongoing prospective cohort study of 121,701 female nurses in the United States with followup from 1976 to 2002.

Prospective study of chemical exposures and amyotrophic lateral sclerosis.

Background: Although environmental toxins, including pesticides, are suspected of contributing to the risk of amyotrophic lateral sclerosis (ALS), no data exist from large prospective investigations. This study assessed the association between exposure to chemicals and risk of ALS in a prospective cohort study.

Methods: The relation between self-report of regular exposure to 11 different chemical classes or x rays and ALS mortality among over 1 million participants in the American Cancer Society's Cancer Prevention Study II was prospectively assessed.

Obesity and restless legs syndrome in men and women.

Background: Obesity and restless legs syndrome (RLS) are both associated with hypofunction of dopamine in the CNS. We therefore examined whether individuals who are obese have an increased risk of RLS in two ongoing US cohorts, the Nurses' Health Study II and the Health Professional Follow-up Study.

Methods: We included 65,554 women and 23,119 men free of diabetes, arthritis, and pregnancy in the current analyses.

Prenatal and perinatal factors and risk of multiple sclerosis.

Background: A potential role of prenatal and perinatal exposures in autoimmunity has been hypothesized, but few studies have examined the relation between various prenatal and perinatal factors and the risk of multiple sclerosis (MS).

Methods: The study population included participants in the Nurses' Health Studies--2 prospective cohorts that together comprise 238,381 female nurses, who self-reported exposure to prenatal and perinatal factors. In addition, 35,815 nurses' mothers participated by providing detailed information regarding experiences surrounding their daughter's birth.

Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies.

Background: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance.

Objective: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age.