A Predictive Autoantibody Signature in Multiple Sclerosis.

Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. Here, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster of PwMS that share an autoantibody signature against a common motif that has similarity with many human pathogens.

Spinal Cord Atrophy Predicts Progressive Disease in Relapsing Multiple Sclerosis.

Objective: A major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS).

Methods: From a single-center observational study, all RRMS (n = 360) and SPMS (n = 47) patients and 80 matched controls were evaluated.

Silent progression in disease activity-free relapsing multiple sclerosis.

Objective: Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability.

Pilot studies of estrogen-related physical findings in infants.

Background: Soy formula containing estrogenic isoflavones is widely used in the United States. Infants consuming soy formula exclusively have high isoflavone exposures. We wanted to study whether soy formula prolonged the physiologic estrogenization of newborns, but available quantitative descriptions of the natural history of breast and genital development are inadequate for study design.

Some evidence of effects of environmental chemicals on the endocrine system in children.

Pollutant chemicals that are widespread in the environment can affect endocrine function in laboratory experiments and in wildlife. Although human beings are commonly exposed to such pollutant chemicals, the exposures are generally low and clear effects on endocrine function from such exposures have been difficult to demonstrate. Human data including both exposure to the chemical agent and the endocrine outcome are reviewed here, including age at weaning, age at puberty, anogenital distance, and sex ratio at birth, and the strength of the evidence are discussed.

Recall of a lead-contaminated vitamin and mineral supplement in a clinical trial.

Purpose: The Treatment of Lead-exposed Children (TLC) trial tested whether developmental outcome differed between children treated for lead poisoning with succimer or placebo. On 7 July 1997, TLC was informed that the vitamin and mineral supplements it gave to all children were contaminated with about 35 microg of lead per tablet.

Methods: TLC recalled the contaminated supplements and measured the children's exposure.

Evidence of effects of environmental chemicals on the endocrine system in children.

Pollutant chemicals that are widespread in the environment can affect endocrine signaling, as evidenced in laboratory experiments and in wildlife with relatively high exposures. Although humans are commonly exposed to such pollutant chemicals, the exposures are generally low, and clear effects on endocrine function from such exposures have been difficult to demonstrate. Several instances in which there are data from humans on exposure to the chemical agent and the endocrine outcome are reviewed, including age at weaning, age at puberty, and sex ratio at birth, and the strength of the evidence is discussed.

Assessment of cleaning to control lead dust in homes of children with moderate lead poisoning: treatment of lead-exposed children trial.

In this article we describe the assessment and control of lead dust exposure in the Treatment of Lead-exposed Children (TLC) Trial, a clinical trial of the effects of oral chelation on developmental end points in urban children with moderately elevated blood lead levels. To reduce potential lead exposure from settled dust or deteriorated paint during the drug treatment phase of the trial, the homes of 765 (98%) of the randomized children (both active and placebo drug treatment groups) were professionally cleaned. Lead dust measurements were made in a sample of 213 homes before and after cleaning.

Do children with falling blood lead levels have improved cognition?

Objective: Exposure to lead at levels encountered by urban children impairs cognitive development. An observational study suggested improvement in IQ when blood lead level fell, but the only randomized trial of chelation showed no benefit in IQ.

Methods: We did a new analysis of the data from the clinical trial using change in blood lead level as the independent variable.

The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead.

Background: Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment.

Methods: We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter (1.

Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene.

Objectives: Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) are ubiquitous toxic environmental contaminants. Prenatal and early life exposures affect pubertal events in experimental animals. We studied whether prenatal or lactational exposures to background levels of PCBs or DDE were associated with altered pubertal growth and development in humans.

X-ray evidence of increased asbestos exposure in the US population from NHANES I and NHANES II, 1973-1978. National Health Examination Survey.

Objectives: Jobs involving heavy asbestos exposure increase risk for lung cancer and mesothelioma substantially, and low-level exposures may carry some risk. At least one indicator of asbestos exposure, mesothelioma, has been increasing in the US for decades. We investigated the prevalence of another indicator, pleural thickening on x-ray, in a defined sample of the US population.

Chemical contaminants, pharmacokinetics, and the lactating mother.

We review the commonly occurring persistent pesticides and industrial chemicals in breast milk. These chemicals are dichlorodiphenyl trichloroethane as dichlorodiphenyl dichloroethene dieldrin, chlordane as oxychlordane, heptachlor, polychlorinated biphenyls, polychlorinated dibenzofurans, and polychlorinated dibenzodioxins. We present a worked example of the kinds of pharmacokinetic assumptions and calculations necessary for setting regulatory limits of contaminants in the food supply, calculating dose of chemical contaminants to the nursed infant, converting risks from lifetime exposure in laboratory animals to risks for short-term exposure in humans, and estimating the excess cancer risk to the nursed infant.

Dermatological findings in children exposed transplacentally to heat-degraded polychlorinated biphenyls in Taiwan.

We studied 128 children who were transplacentally exposed to polychlorinated biphenyls and dibenzofurans in Taiwan, their parents and siblings who were directly exposed, and 115 control children. Direct exposure of the mothers stopped in 1979 and the children were born as late as 1985. At birth, exposed children had increased rates of hyperpigmentation, eyelid swelling and discharge, deformed nails, acne, natal teeth and swollen gums compared to controls.

Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan.

In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by thermally degraded polychlorinated biphenyls. Because these chemicals persist in human tissue, children born to female patients after the outbreak were exposed in utero. In 1985, 117 children born to affected women and 108 unexposed controls were examined and evaluated.

Urinary porphyrins in children exposed transplacentally to polyhalogenated aromatics in Taiwan.

In 1979, there was a large (greater than 2,000 cases) outbreak of poisoning due to contaminated rice oil in central Taiwan. The causal agent was a mixture of thermally degraded polychlorinated biphenyls (PCBs), polychlorinated quaterphenyls, and polychlorinated dibenzofurans, which had become mixed with the oil during processing. Patients remained symptomatic for several years afterward, and the chemicals persisted in their tissue.

US prevalence of occupational pleural thickening. A look at chest X-rays from the first National Health and Nutrition Examination Survey.

The prevalence of occupational pleural thickening in the United States in the mid-1970s was estimated; since asbestos often produces pleural thickening, this estimate in turn was used to estimate the prevalence of asbestos exposure. Chest x-rays obtained by the 1971-1975 National Health and Nutrition Examination Survey were reread by three readers using the International Labour Office criteria for diagnosis of pleural thickening consistent with dust exposure. All 289 x-rays showing any pleural abnormalities plus a 3-to-1 age-, sex-, and race-matched control series were reread.