Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Cortisol in hair measured in young adults - a biomarker of major life stressors?

<p>Abstract</p> <p>Background</p> <p>Stress as a cause of illness has been firmly established. In public health and stress research a retrospective biomarker of extended stress would be an indispensible aid. The objective of this pilot study was to investigate whether concentrations of cortisol in hair correlate with perceived stress, experiences of serious life events, and perceived health in young adults.</p> <p>Methods</p> <p>Hair samples were cut from the posterior vertex area of (n = 99) university students who also answered a questionnaire covering experiences of serious life events, perceived Stress Scale and perceived health during the last three months. Cortisol was measured using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised.</p> <p>Results</p> <p>Mean cortisol levels were significantly related to serious life events (p = 0.045), weakly negatively correlated to perceived stress (p = 0.025, r = -0.061) but nor affected by sex, coloured/permed hair, intake of pharmaceuticals or self-reported health. In a multiple regression model, only the indicator of serious life events had an independent (p = 0.041) explanation of increased levels of cortisol in hair. Out of four outliers with extremely high cortisol levels two could be contacted, both reported serious psychological problems.</p> <p>Conclusions</p> <p>These findings suggest that measurement of cortisol in hair could serve as a retrospective biomarker of increased cortisol production reflecting exposure to major life stressors and possibly extended psychological illness with important implications for research, clinical practice and public health. Experience of serious life events seems to be more important in raising cortisol levels in hair than perceived stress.</p

Adverse Effects of Methylmercury: Environmental Health Research Implications

Background: The scientific discoveries of health risks resulting from methylmercury exposure began in 1865 describing ataxia, dysarthria, constriction of visual fields, impaired hearing, and sensory disturbance as symptoms of fatal methylmercury poisoning. Objective: Our aim was to examine how knowledge and consensus on methylmercury toxicity have developed in order to identify problems of wider concern in research. Data sources and extraction: We tracked key publications that reflected new insights into human methylmercury toxicity. From this evidence, we identified possible caveats of potential significance for environmental health research in general. Synthesis: At first, methylmercury research was impaired by inappropriate attention to narrow case definitions and uncertain chemical speciation. It also ignored the link between ecotoxicity and human toxicity. As a result, serious delays affected the recognition of methylmercury as a cause of serious human poisonings in Minamata, Japan. Developmental neurotoxicity was first reported in 1952, but despite accumulating evidence, the vulnerability of the developing nervous system was not taken into account in risk assessment internationally until approximately 50 years later. Imprecision in exposure assessment and other forms of uncertainty tended to cause an underestimation of methylmercury toxicity and repeatedly led to calls for more research rather than prevention. Conclusions: Coupled with legal and political rigidity that demanded convincing documentation before considering prevention and compensation, types of uncertainty that are common in environmental research delayed the scientific consensus and were used as an excuse for deferring corrective action. Symptoms of methylmercury toxicity, such as tunnel vision, forgetfulness, and lack of coordination, also seemed to affect environmental health research and its interpretation

Adverse Effects of Methylmercury: Environmental Health Research Implications

Background: The scientific discoveries of health risks resulting from methylmercury exposure began in 1865 describing ataxia, dysarthria, constriction of visual fields, impaired hearing, and sensory disturbance as symptoms of fatal methylmercury poisoning. Objective: Our aim was to examine how knowledge and consensus on methylmercury toxicity have developed in order to identify problems of wider concern in research. Data sources and extraction: We tracked key publications that reflected new insights into human methylmercury toxicity. From this evidence, we identified possible caveats of potential significance for environmental health research in general. Synthesis: At first, methylmercury research was impaired by inappropriate attention to narrow case definitions and uncertain chemical speciation. It also ignored the link between ecotoxicity and human toxicity. As a result, serious delays affected the recognition of methylmercury as a cause of serious human poisonings in Minamata, Japan. Developmental neurotoxicity was first reported in 1952, but despite accumulating evidence, the vulnerability of the developing nervous system was not taken into account in risk assessment internationally until approximately 50 years later. Imprecision in exposure assessment and other forms of uncertainty tended to cause an underestimation of methylmercury toxicity and repeatedly led to calls for more research rather than prevention. Conclusions: Coupled with legal and political rigidity that demanded convincing documentation before considering prevention and compensation, types of uncertainty that are common in environmental research delayed the scientific consensus and were used as an excuse for deferring corrective action. Symptoms of methylmercury toxicity, such as tunnel vision, forgetfulness, and lack of coordination, also seemed to affect environmental health research and its interpretation

The gender specific frequency of risk factor and CHD diagnoses prior to incident MI: A community study

BACKGROUND: CHD is a chronic disease often present years prior to incident AMI. Earlier recognition of CHD may be associated with higher levels of recognition and treatment of CHD risk factors that may delay incident AMI. To assess timing of CHD and CHD risk factor diagnoses prior to incident AMI. METHODS: This is a 10-year population based medical record review study that included all medical care providers in Olmsted County, Minnesota for all women and a sample of men residing in Olmsted County, MN with confirmed incident AMI between 1995 and 2000. RESULTS: All medical care for the 10 years prior to incident AMI was reviewed for 150 women and 148 men (38% sample) in Olmsted County, MN. On average, women were older than men at the time of incident AMI (74.7 versus 65.9 years, p < 0.0001). 30.4% of the men and 52.0% of the women received diagnoses of CHD prior to incident AMI (p = 0.0002). Unrecognized and untreated CHD risk factors were present in both men (45% of men 5 years prior to AMI) and women (22% of women 5 years prior to first AMI), more common in men and those without a diagnosis of CHD prior to incident AMI (p < 0.0001). CONCLUSION: A CHD diagnosis prior to incident AMI is associated with higher rates of recognition and treatment of CHD risk factors suggesting that diagnosing CHD prior to AMI enhances opportunities to lower the risk of future CHD events

The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner

Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O6-methyldeoxyguanosine lesions, O6-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O6-mG DNA methyltransferase (MGMT) showed elevated O6-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease

INCIDENCE AND PREVALENCE OF HUNTINGTONS-DISEASE IN OLMSTED COUNTY, MINNESOTA (1950 THROUGH 1989)

Objective: To calculate average annual incidence rates for Huntington's disease (HD) from 1950 through 1989 and to estimate prevalence rates of the disease for January 1, 1960, and January 1, 1990