The purpose of this study was to validate the accuracy and acceptability of the new VitalSense(R) telemetric physiological monitoring system (Mini Mitter Co., Inc., Bend, OR). It consists of a receiver/monitor and a thermistor-based ingestible capsule for core body temperature measurement. For comparison, each subject was also monitored with a standard thermistor probe inserted 11 cm beyond the anal sphincter (Mini-Logger(R) Series 2000). Both the measurement systems have specified accuracy of +/- 0.1 degreesC.Ten volunteers, four females, six males, mean age 51.1 +/- 11.8 years, gave informed consent to wear the two systems for the duration of the passage of the temperature capsule through their digestive tracts. Minute-by-minute comparisons were made between the temperatures recorded by the two systems. Parameters reported include: average transit time of the capsule; temperature at each minute of the experiment; mean difference in temperature at each time point; correlation coefficient for the two temperature measurements; and number of missed data points for each system. Mean capsule transit time was 48.6 +/- 35.5 h with a range of 12.4-136.2 h. The mean temperature for all subjects was 36.93 degreesC +/- 0.15 degreesC and 36.96 degreesC +/- 0.16 degreesC for the capsule and rectal probe respectively, with no significant difference between the means. The mean difference between readings (capsule-rectal probe) was 0.04 degreesC +/- 0.03 degreesC. There was a significant correlation between the capsule and rectal probe temperatures, R-2 = 0.80,p < 0.05 and R-2 = 0.90,p < 0.05 for all data points and quiescent periods respectively. Of the average 2916 +/- 2132 data points per subject, there was a significant (p < 0.05) difference in data points lost, 105 +/- 120 with VitalSense vs. 449 +/- 697 with the rectal probe. The percentage of missing data points was 3.1% +/- 2.5% for the capsule (monitor out of the one-meter range of the capsule) and 11.4% +/- 15.9% for the rectal probe (primarily due to probe slippage, but also due to removal for personal hygiene). The data support the finding that the VitalSense core body temperature monitoring system is at least as accurate as rectal probe monitors and the subjects found it to be much more acceptable. (C) 2004 Elsevier Ltd. All rights reserved.

1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the ε4 allele of the apolipoprotein E gene (on chromosome 19) is now recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease.

Diffuse axonal injury (DAI) in the central nervous system is a common cause of post‐traumatic coma and may result in varying degrees of disability up to and including the vegetative state. Experimental studies in man and animals have previously relied upon semiquantitative grading systems for determining the relationship between the extent of DAI and the clinical features of patients. Using β‐amyloid precursor protein immunocytochemistry for the detection of DAI in sections of corpus callosum from 15 cases of fatal head injury, we have developed a quantitative image analysis technique for the assessment of axonal injury. This new method is objective and reproducible and should allow better correlation with biomechanical, radiological, and clinical parameters to increase our understanding of DAI.

The role of glial inflammatory processes in Alzheimer's disease has been highlighted by recent epidemiological work establishing head trauma as an important risk factor, and the use of anti‐inflammatory agents as an important ameliorating factor, in this disease. This review advances the hypothesis that chronic activation of glial inflammatory processes, arising from genetic or environmental insults to neurons and accompanied by chronic elaboration of neuroactive glia‐derived cytokines and other proteins, sets in motion a cytokine cycle of cellular and molecular events with neurodegenerative consequences. In this cycle, interleukin‐1 is a key initiating and coordinating agent. Interleukin‐1 promotes neuronal synthesis and processing of the β‐amyloid precursor protein, thus favoring continuing deposition of β‐amyloid, and activates astrocytes and promotes astrocytic synthesis and release of a number of inflammatory and neuroactive molecules. One of these, S100β, is a neurite growth‐promoting cytokine that stresses neurons through its trophic actions and fosters neuronal cell dysfunction and death by raising intraneuronal free calcium concentrations. Neuronal injury arising from these cytokine‐induced neuronal insults can activate microglia with further overexpression of interleukin‐1, thus producing feedback amplification and self‐propagation of this cytokine cycle. Additional feedback amplification is provided through other elements of the cycle. Chronic propagation of this cytokine cycle represents a possible mechanism for progression of neurodegenerative changes culminating in Alzheimer's disease.

Chronic overexpression of the neurite growth-promoting factor S100β has been implicated in the pathogenesis of neuritic plaques in Alzheimer’s disease. Such plaques are virtually universal in middle-aged Down’s syndrome, making Down’s a natural model of Alzheimer’s disease. We determined numbers of astrocytes overexpressing S100β, and of neurons overexpressing β-amyloid precursor protein (β-APP), and assayed for neurofibrillary tangles in neocortex of 20 Down’s syndrome patients (17 weeks gestation to 68 years). Compared to controls, there were twice as many S100β-immunoreactive (S100β+) astrocytes in Down’s patients at all ages: fetal, young, and adult (p = 0.01, or better, in each age group). These were activated (i.e., enlarged), and intensely immunoreactive, even in the fetal group. There were no neurofibrillary changes in fetal or young Down’s patients. The numbers of S100β+ astrocytes in young and adult Down’s patients correlated with the numbers of neurons overexpressing β-APP (p < 0.05). Our findings are consistent with the idea that conditions—including Down’s syndrome—that promote chronic overexpression of S100β may confer increased risk for later development of Alzheimer’s disease.

Recreational fishers participating in a 12 mo diary survey provided per-trip data on number of snapper Pagrus auratus caught per unit effort (CPUE) in upper North Island, New Zealand. These data were analyzed for seasonal trends, differences between lunar quarters, and for an ordinal relationship with the daily ranking (on a scale of 1 to 5) of the duration of active feeding as predicted by a Maori fishing calendar. A strong seasonal trend explained 30% of the variation in CPUE, with CPUE peaking in early April and subsequently declining until late August. There was modest evidence of both a difference in CPUE between lunar quarters, and a relationship with the rankings of feeding duration given by the fishing calendar (p-values approximate to 0.1), but neither explained more than 2% of the variation in seasonally detrended CPUE. Days having the highest ranking of feeding duration sometimes had below average CPUE, but were never among the extremely low CPUE days. Conversely, days having the lowest ranking of feeding duration sometimes had above average CPUE, but never had extremely high CPUE.

Phosphorus magnetic resonance spectroscopy ( 31 P MRS) was used to determined whether focal cerebral injury caused by unilateral carotid artery occlusion and graded hypoxia in developing rats led to a delayed impairment of cerebral energy metabolism and whether the impairment was related to the magnitude of cerebral infarction. Forty-two 14-day-old Wistar rats were subjected to right carotid artery ligation, followed by 8% oxygen for 90 min. Using a 7T MRS system, 31 P brain spectra were collected during the period from before until 48 h after hypoxia-ischaemia. Twenty-eight control animals were studied similarly. In controls, the ratio of the concentration of phosphocreatine ([PCr]) to inorganic orthophosphate ([Pi]) was 1.75 (SD 0.34) and nucleotide triphosphate (NTP) to total exchangeable phosphate pool (EPP) was 0.20 (SD 0.04): both remained constant. In animals subjected to hypoxia-ischaemia, [PCr] to [Pi] and [NTP] to [EPP] were lower in the 0- to 3-h period immediately following the insult: 0.87 (0.48) and 0.13 (0.04), respectively. Values then returned to baseline level, but subsequently declined again: [PCr] to [Pi] at −0.02 h −1 ( P <0.0001). [PCr] to [Pi] attained a minimum of 1.00 (0.33) and [NTP] to [EPP] a minimum of 0.14 (0.05) at 30–40 h. Both ratios returned towards baseline between 40 and 48 h. The late declines in high-energy phosphates were not associated with a fall in pH i . There was a significant relation between the extent of the delayed impairment of energy metabolism and the magnitude of the cerebral infarction ( P <0.001). Transient focal hypoxia-ischaemia in the 14-day-old rat thus leads to a biphasic disruption of cerebral energy metabolism, with a period of recovery after the insult being followed by a secondary impaiment some hours later.

There is increasing evidence of a link between head injury and the subsequent onset of Alzheimer’s disease. Deposits of amyloid β-protein (Aβ) are found not only in cases of dementia pugilistica but in some 30% of patients dying after a single episode of severe head injury. Detailed clinicopathological studies have shown that Aβ deposition is most likely, but not exclusively, to occur, the older the patient at the time of injury, and if the injury is the result of a fall. Distribution studies have shown that the Aβ is widely deposited in the neocortex and there is no apparent association with any of the multiple primary or secondary pathologies of traumatic brain injury. There is an increased expression of β-APP particularly in the pre-α cells of the entorhinal cortex and in areas of axonal damage. Recent molecular genetic studies have shown that there is a strong association between deposits of Aß and the apolipoprotein E genotype of the individual.

Neurofibrillary lesions such as neurofibrillary tangles, neurites and neuropil threads are used as neuropathological markers of Alzheimer's disease (AD). However these lesions are also seen in non-demented elderly cases as well as in several other disorders such as Down's syndrome (DS), dementia pugilistica (DP) and Parkinson's disease. Quantitative studies may therefore help in understanding the pathophysiological role of these lesions. Using a novel image analysis technique we have quantified the extent of neurofibrillary damage in AD, DS and DP. We have found that the extent of neurofibrillary change did not significantly differ beween AD and DS, though there were also strong parallels between AD and DP. We conclude that both genetic (as in DS) and environmental (as in DP) risk factors for AD-type pathology provide a similar pattern of neurofibrillary degeneration to that in AD itself suggesting that similar degenerative mechanisms might be triggered in all three conditions.

The neuropathological diagnosis of Alzheimer's disease requires an assessment of the quantity of pathology present. Advances in molecular biology have highlighted the role of β-amyloid precursor protein (βAPP) in the pathogenesis of the disease. This protein is found in neurons and other cells and many neuropathological studies would benefit from a method which generates reliable data on the numbers of cells containing significant amounts of the protein. Classically, generation of such data would have involved laborious manual counting. This particular approach carries low levels of inter- and intra-rater reliability and is much dependent on the skill and experience of the operator. We have used immunocytochemistry to specifically define a single cell population, pre-α cells, containing βAPP, and have developed a computerized cell counting programme that can reliably quantify these cells in human post-mortem brain samples. We have obtained a high level of accuracy (>95%) and efficiency in identifying and quantifying target cells and have demonstrated that our protocol can be used effectively by both novice and expert. This method could be easily configured to provide quantitative data for a wide range of immunocytochemically defined cell populations.

In a previous publication we hypothesized that Alzheimer's disease (AD) can be induced by the age-related increase in expression of beta-amyloid precursor protein (beta APP) in the medial temporal lobe. Head injury has also been identified as a risk factor for AD and as such, similarities should exist between the pathology found after head injury and the earliest stages of pathology in AD. In this study, we have quantified the number of beta APP-immunoreactive neurones in the medial temporal cortex (pre-alpha cells, layer II) of 13 head injured and 17 control patients. Significantly more beta APP immunoreactive neurones were observed in head injury cases (mean 18.4 per cluster) compared with controls (mean 13.4 per cluster, p < 0.05). These data provide a mechanism to explain how an environmental event such as head injury can generate the same molecular pathology (increased neuronal beta APP) as is found in the earliest stages of AD.

beta-Amyloid protein (beta A4) deposition was characterised in the sulci and gyri of frontal cortex in 14 cases of Alzheimer's disease. A quantitative study was made of two distinct plaque sub-types (diffuse and classic) using immunocytochemistry and image analysis using a discriminant function design. As reported previously more beta A4 was observed in sulci than gyri. Diffuse plaques were more numerous than classic plaques in sulci and gyri (P less than 0.01). Classic plaques were more abundant in the sulci (P less than 0.01). Increased beta A4 deposition in the sulci is accounted for by increased numbers of classic plaques. No correlation was observed between the numbers of diffuse and classic plaques in either region. Our data suggest that the two plaque types form discrete populations and that their evolution is governed by distinct pathophysiological parameters.