Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and an oxidized amino acid, nitrotyrosine in vulnerable neurons of patients with Alzheimer disease (AD). To determine whether oxidative damage is an early- or end-stage event in the process of neurodegeneration in AD, we investigated the relationship between neuronal 8OHG and nitrotyrosine and histological and clinical variables, i.e. amyloid-beta (A beta) plaques and neurofibrillary tangles (NFT), as well as duration of dementia and apolipoprotein E (ApoE) genotype. Our findings show that oxidative damage is quantitatively greatest early in the disease and reduces with disease progression. Surprisingly, we found that increases in A beta deposition are associated with decreased oxidative damage. These relationships are more significant in ApoE epsilon4 carriers. Moreover, neurons with NFT show a 40%-56% decrease in relative 8OHG levels compared with neurons free of NFT. Our observations indicate that increased oxidative damage is an early event in AD that decreases with disease progression and lesion formation. These findings suggest that AD is associated with compensatory changes that reduce damage from reactive oxygen.
Autonomic dysreflexia (AD) is an uncommon but potentially life-threatening clinical syndrome consisting of acute episodes of excessive, uncontrolled sympathetic output that may occur in quadriplegics and in paraplegics whose spinal cord lesions are above the level of T6. These uncontrolled bouts of sympathetic output can cause transient and pronounced elevations of blood pressure that on occasion can lead to serious sequela such as the precipitation of a hypertensive intracerebral hemorrhage. The episodes of AD are often triggered by some type of noxious stimulus such as a distended urinary bladder or a fecal impaction. We present the case of a 62-year-old man with a history of quadriplegia resulting from a diving accident 40 years ago that was complicated clinically by episodes of autonomic dysreflexia. While hospitalized, he experienced an episode of autonomic dysreflexia with severe hypertension, which was soon followed by neurologic deterioration and death. Antemortem imaging revealed a large hypertensive-type intracerebral hemorrhage originating in his right caudate nucleus. Although his death at first appeared to be a natural death due to a spontaneous hypertensive-type intracerebral hemorrhage, his clinically documented autonomic dysreflexia convincingly linked the remote spinal cord injury and the fatal intracerebral hemorrhage, engendering an accidental manner of death.
Background Accelerometers can objectively measure steps taken per day in individuals without gait deficits, but accelerometers also have the ability to estimate frequency, intensity, and duration of physical activity. However, thresholds to distinguish varying levels of activity intensity using the Actical brand accelerometer are standardized only for the general population and may underestimate intensity in stroke. Objective To derive Actical activity count thresholds specific to stroke disability for use in more accurately gauging time spent at differing activity levels. Methods Men (n=18) and women (n=10) with chronic hemiparetic gait (4±2 years latency, 43% Caucasian, 56% African American, ages of 47–83 yrs, BMI 19 – 48 kg/m2) participated in the study. Actical accelerometers were placed on the non-paretic hip to obtain accelerometry counts during eight activities of varying intensity: 1) watching TV; 2) seated stretching; 3) standing stretching; 4) floor sweeping; 5) stepping in place; 6) over-ground walking; 7) lower speed treadmill walking (1.0 mph at 4% incline); and 8) higher speed treadmill walking (2.0 mph at 4% incline). Simultaneous portable monitoring (Cosmed K4b2) enabled quantification of energy cost for each activity in metabolic equivalents (METs, or oxygen consumption in multiples of resting level). Measurements were obtained for 10 min of standard rest and 5 minutes during each of the eight activities. Results Regression analysis yielded the following new stroke-specific Actical minimum thresholds: 125 counts per minute (cpm) for sedentary/light activity, 667 cpm for light/moderate activity, and 1546 cpm for moderate/vigorous activity. Conclusion Our revised cut-points better reflect activity levels after stroke and suggest significantly lower thresholds relative to those observed for the general population of healthy individuals. We conclude that the standard, commonly applied Actical thresholds are inappropriate for this unique population.
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