Peter M. Cummings

Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E.

OBJECTIVES The goal of this study was to determine whether postprandial hyperglycemia, induced by oral glucose loading, attenuates endothelial function in healthy subjects without diabetes and whether coadministration of vitamins C and E could prevent these postprandial changes. BACKGROUND Epidemiologic evidence suggests that postprandial hyperglycemia, below diabetic levels, is a risk factor for cardiovascular disease. Postprandial hyperglycemia may promote atherosclerosis through endothelial dysfunction and oxidative stress. METHODS We evaluated the acute effects of oral glucose loading (75 g), alone and with vitamins C (2 g) and E (800 IU), on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery, in a randomized, double-blind, placebo-controlled, crossover study of 10 healthy volunteers. Changes in the levels of markers of oxidative stress (plasma malondialdehyde and erythrocyte glutathione, glutathione peroxidase and superoxide dismutase) were also assessed. RESULTS Increases in plasma glucose and insulin after glucose loading were unaffected by vitamin coadministration. With glucose loading alone, FMD fell from 6.5+/-2.2 at baseline to 5.4+/-1.7, 3.7+/-2.1*, 4.1+/-3.5* and 5.7+/-1.9% at 1, 2, 3 and 4 h (*p < 0.05 vs. 0 h). In contrast, FMD did not change significantly after glucose plus vitamins (6.4+/-1.3, 7.6+/-1.8, 7.9+/-2.7, 6.9+/-2.3, 6.9+/-1.9% at 0, 1, 2, 3 and 4 h). By two-way repeated measures analysis of variance we found a significant interaction between vitamin treatment and time (p = 0.0003), indicating that vitamins prevented the glucose-induced attenuation of FMD. Oxidative stress markers did not significantly change with glucose loading alone or with vitamins. CONCLUSIONS Oral glucose loading causes an acute, transient decrease of FMD in healthy subjects without diabetes, which is prevented by vitamins C and E.

Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease.

OBJECTIVES The purpose of this study was to determine whether lowering homocysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD). BACKGROUND Elevated plasma homocysteine levels are a risk factor for atherosclerosis. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress. METHODS In a double-blind, placebo-controlled, randomized trial, we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level > or =9 micromol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months. Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment. RESULTS Plasma folate, homocysteine and FMD were unchanged in the placebo group. Compared with placebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduced plasma homocysteine by 11% (p = 0.23) and significantly improved FMD from 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlated with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FMD from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-mediated dilation did not change significantly in any group. CONCLUSIONS Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis. Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events.

Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis

Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues.

Neuroimaging assessment of memory-related brain structures in a rat model of acute space-like radiation.

To investigate the acute effects on the central nervous system (CNS) of 56Fe radiation, a component of high‐energy charged particles (HZE) in space radiation, using quantitative magnetic resonance imaging (MRI) noninvasively.

Sudden death of a 7-year-old boy due to undiagnosed glioblastoma.

We present a case of sudden death of a 7-year-old boy who at autopsy was found to have an undiagnosed glioblastoma. The boy was asymptomatic until 2 hours before death complaining of a headache and was later found unresponsive in bed. A medicolegal autopsy was notable for a large hemorrhagic mass of the right frontal lobe, which on analysis was diagnostic of a glioblastoma. We feel that this is a unique case for 2 main reasons; high-grade gliomas of the cerebral cortex are rare in the pediatric population, and it is unusual for a large neoplasm to remain asymptomatic until 2 hours prior to death.

Tau accumulations in the brains of woodpeckers

Woodpeckers experience forces up to 1200–1400 g while pecking. It is assumed due to evolutionary adaptations, the woodpecker is immune to brain injury. This assumption has led to the use of the woodpecker as a model in the development of sports safety equipment such as football helmets. However, it is unknown at this time if the woodpecker brain develops neuro-trauma in relation to the high g-forces experienced during pecking. The brains of 10 ethanol preserved woodpeckers and 5 ethanol preserved red-winged black bird experimental controls were examined using Gallyas silver stain and anti-phospho-tau. The results demonstrated perivascular and white matter tract silver-positive deposits in eight out of the 10 woodpecker brains. The tau positive accumulations were seen in white matter tracts in 2 of the 3 woodpeckers examined. No staining was identified in control birds. The negative staining of controls birds contrasted with the diffuse positive staining woodpecker sections suggest the possibility that pecking may induce the accumulation of tau in the woodpecker brain. Further research is needed to better understand the relationship.

Homicidal Violence Among National Football League Athletes

Given the concerns regarding chronic traumatic encephalopathy and its potential association with violent behavior in football players, we investigated the rates of deaths and arrests related to homicide among the National Football League (NFL) population. In order to accomplish this, we performed a retrospective analysis of the 27 155 individuals who had played, or are currently playing, professional football since its inception in 1920. The number of observed homicides in this cohort was compared to the number of expected homicides using the Centers for Disease Control and Prevention annual tables. Information regarding player cause of death was obtained from web-based sources. We identified 17 (0.27%) homicides among the 6356 NFL player deaths. The average age of individuals dying as the result of homicide was 31.4 years (range 24-50 years). Gunshot wound was the leading cause of death. The standardized mortality ratio for death by homicide was historically below 5%. As compared to the general US population, there were about 70% fewer deaths by homicide in the NFL population than would be expected. Our study also found only 0.04% of the NFL player population has ever been the focus of a homicide investigation, with only 0.02% of the NFL player population having been convicted. Our findings suggest homicidal violence among NFL players is rare, as NFL players have substantially lower rates of dying and being arrested as a consequence of homicidal violence compared to the general US population.