The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M J Ball.
Explore the source record for details and available documents.
OBJECTIVE: To describe the relationship between neuropathologic aging and longitudinal measures of cognitive function in healthy oldest old individuals. METHODS: Nondemented individuals without cardiovascular or other age-associated diseases of age > or =85 years were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to clinical status, cognitive measures, and rate of cognitive change. RESULTS: Among 19 healthy individuals, 10 became demented or had incipient dementia develop. Clinical status and rate of change in cognitive scores correlated with increasing brain lesion burden, particularly in neocortical regions. Compared to demented individuals, nondemented individuals had few or no neocortical NFT (p = 0.009) or SP (p = 0.001). There was a strong correlation between rate of cognitive change on Mini-Mental State Examination (MMSE) and neocortical NFT (r = 0.859, p = 0.001). The few NFT and SP in nondemented patients had a predilection for limbic areas. CONCLUSIONS: These results support a continuum in which AD is infrequent in the healthy, cognitively stable, oldest old. The minimal abnormalities in cognitively stable individuals are consistent with the notion that preclinical pathologic AD precedes obvious cognitive impairment. Longitudinal cognitive testing shows an increased burden of neuropathologic changes in those who have cognitive decline but are not functionally impaired and do not meet criteria for the diagnosis of dementia. The strong relationship between cumulative pathologic changes and rate of cognitive decline suggests that these lesions may have clinical consequences at any age and are not likely to be benign senescent changes.
Vegetarians have a lower incidence of many chronic diseases than omnivores. However, vegetarian diets could potentially result in lower intakes of some minerals, particularly Zn. In a cross-sectional study, dietary Zn intake was measured using 12 d weighed records in ninety-nine vegetarians (ten vegans) aged 18-50 years and forty-nine age- and sex-matched omnivores. In men, the mean daily Zn intake and Zn density values were similar in omnivores, ovolactovegetarians and vegans, but in women they were significantly lower in vegetarians (mean intake 6.8 mg v. 8.4 mg in omnivores) and few achieved the recommended intake. Significantly more vegetarian than omnivorous women had a daily Zn intake < 6 mg (44% v. 13%). Mean serum Zn concentrations were similar in female omnivores and vegetarians, despite the differences in intake. However, omnivorous men had a lower mean serum Zn concentration (0.85 microgram/ml v. 0.95 microgram/ml) and more subjects had levels below the reference range of 0.72-1.44 micrograms/ml than ovolactovegetarians (P < 0.01). Overall more women than men had low Zn concentrations; and these women generally had intakes below 6 mg/d. There was a significant correlation between serum Zn concentration and dietary Zn density in vegetarians, especially females (P < 0.001), but not in omnivores. Ovolactovegetarians did not have a significantly greater risk of low Zn status than omnivores.
A randomised crossover dietary intervention study was performed to evaluate the effects of replacing meat protein in the diet with a soyabean product, tofu, on blood concentrations of testosterone, dihydrotestosterone, androstanediol glucuronide, oestradiol, sex hormone-binding globulin (SHBG), and the free androgen index (total testosterone concentration/SHBG concentration x 100; FAI). Forty-two healthy adult males aged 35-62 years were studied. Diets were isoenergetic, with either 150 g lean meat or 290 g tofu daily providing an equivalent amount of macronutrients, with only the source of protein differing between the two diets. Each diet lasted for 4 weeks, with a 2-week interval between interventions. Fasting blood samples were taken between 07.00 and 09.30 hours. Urinary excretion of genistein and daidzein was significantly higher after the tofu diet (P < 0.001). Blood concentrations of sex hormones did not differ after the two diets, but the mean testosterone:oestradiol value was 10% higher (P = 0.06) after the meat diet. SHBG was 3% higher (P = 0.07), whereas the FAI was 7% lower (P = 0.06), after the tofu diet compared with the meat diet. There was a significant correlation between the difference in SHBG and testosterone:oestradiol and weight change. Adjusting for weight change revealed SHBG to be 8.8% higher on the tofu diet (mean difference 3 (95% CI 0.7, 5.2) nmol/l; P = 0.01) and testosterone:oestradiol to be significantly lower, P = 0.049). Thus, replacement of meat protein with soyabean protein, as tofu, may have a minor effect on biologically-active sex hormones, which could influence prostate cancer risk. However, other factors or mechanisms may also be responsible for the different incidence rates in men on different diets.
No longer focused on mere automation of manual processes, healthcare technology is poised to transform practice. Healthcare information systems can extend and enhance the memory; streamline administrative processes; provide access to information where, when, and how it is needed; and manage the cost of care while protecting and improving clinical quality and customer satisfaction. To reap the benefits of information systems, healthcare professionals must take stock of the industry's current position on the road to transformation and determine how to manage the journey ahead. This article explores healthcare information technology trends, discusses emerging technologies such as the Internet and the computerized patient record, and offers future recommendations for achieving technology integration and acceptance. Key to this discussion is the belief that people-based skills such as cooperation, leadership, and creative thinking are just as important as--if not more important than--the actual technology.
Explore the source record for details and available documents.
OBJECTIVE: The study was designed to investigate the iron intake and status of Australian, male vegetarians aged between 20 and 50 y. DESIGN: Cross-sectional comparison of male vegetarians and age/sex matched omnivores. SETTING: Free-living community subjects. SUBJECTS: 39 ovolactovegetarians, 10 vegans and 25 omnivores were recruited by local advertisement. OUTCOME MEASURES: A 12-d semiquantitative dietary record to assess iron and zinc intake. Iron status was assessed by measurement of serum ferritin and haemoglobin concentrations. RESULTS: Mean (s.d.) daily iron intakes of both the ovolactovegetarians (20.4 (7.7) mg/d) and vegans (22.9 (6.2) mg/d), were significantly higher than the omnivores' intake of 15.8 (4.5) mg/d. Ovo-lactovegetarians and vegans had significantly (P < 0.001 and P < 0.05, respectively) lower serum ferritin concentrations than omnivores: mean (s.d.): 64 (46.9), 65 (49.9) and 121 (72.5) ng/ml, respectively. Significantly more ovolactovegetarians and vegans than omnivores had serum ferritin concentrations below 25 ng/ml and below 12 ng/ml (P < 0.05). A higher proportion of omnivores had concentrations above 200 ng/ml (P < 0.05). The differences in serum ferritin concentrations between the vegetarians and omnivores remained significant even after exclusion of iron supplement users. CONCLUSION: Australian male vegetarians had iron intakes higher than those of omnivores and above recommended levels, but their iron status was significantly lower.
BACKGROUND: Gastroplasty results in a considerable reduction in food intake and dramatic weight loss. This is likely to have a nutritional impact, although it is expected that this may be minimised by good advice and supplement use. METHODS: Twenty six obese subjects were studied in detail before and after modified long vertical gastroplasty (MLVG), in a setting where comprehensive nutritional advice on symptom avoidance was readily available and multivitamin supplements advised. Nutritional intake and anthropometry were measured preoperatively and at 2, 5 (n = 22) and 12 months (n = 11) postoperatively. RESULTS: Mean weight loss was 13%, 22% and 31% of initial body weight at the respective time points. Energy intake (EI) was significantly reduced postoperatively, with the mean protein intake being only 40 g/d. At 2 months, mean intakes of iron, calcium and zinc from food were 40%, 71% and 39%, respectively, of the Australian recommended dietary intake (RDI), and iron and zinc intake remained below half the RDI at 5 months. Only regular adherence to the vitamin/mineral supplement, brought iron and calcium intakes close to RDI, but zinc remained low. Haemoglobin and serum ferritin concentrations did not alter significantly and remained within the reference range, but serum folate fell significantly between 5 months and 12 months. By 5 months, 60% of subjects never regurgitated or regurgitated less than once a week. Fresh bread was the least tolerated food. Frequency of regurgitation was not correlated with adequacy of nutrient intake. CONCLUSIONS: The results emphasise the need for regular follow-up of MLVG patients, and nutritional advice which includes diet quality as well as symptom management, and regular intake of the vitamin/mineral supplement for at least a year postoperatively. Low protein intakes, however, remain of potential long-term concern.
BACKGROUND: Despite the possible overall health benefits of a vegetarian diet, there is concern that some vegetarians and infrequent meat eaters, particularly females, may have inadequate iron status because of low or no heme-iron intakes. OBJECTIVE: The objective was to investigate the nutritional intake and iron status of vegetarian women. DESIGN: The nutritional intakes of 50 free-living vegetarian women aged 18-45 y and 24 age-matched omnivorous control women were assessed by using 12-d weighed dietary records. Iron status was assessed by measuring hemoglobin and serum ferritin concentrations. RESULTS: There was no significant difference between mean (+/-SD) daily iron intakes of vegetarians and omnivores (10.7 +/- 4.4 and 9.9 +/- 2.9 mg, respectively), although heme-iron intakes were low in the vegetarians. Vegetarians had significantly lower intakes of protein (P < 0.01), saturated fat (P < 0.01), and cholesterol (P < 0.001), and significantly higher intakes of dietary fiber (P < 0.001) and vitamin C (P < 0.05). Mean serum ferritin concentrations were significantly lower (P = 0.025) in vegetarians (25.0 +/- 16.2 microg/L) than in omnivores (45.5 +/- 42.5 microg/L). However, similar numbers of vegetarians (18%) and omnivores (13%) had serum ferritin concentrations <12 microg/L, which is a value often used as an indicator of low iron stores. Hemoglobin concentrations were not significantly different. CONCLUSION: It is important that both vegetarian and omnivorous women maintain an adequate iron status and follow dietary practices that enhance iron absorption.
As healthcare changes, HIM professionals must act as individuals to keep pace with the transformation. Educational changes in HIM curricula are evolving, but HIM professionals must take responsibility for their education to take advantage of opportunities presented by new information technologies.
We report the neuropathological features in 6 members of a Volga German family with autosomal dominant Alzheimer's disease linked to chromosome 1 who had a presenilin-2 mutation (N141I). The most significant feature in this family was the presence of severe or moderately severe amyloid angiopathy in five family members with clinical dementia. The index case with the presenilin-2 mutation had late-onset dementia at age 73 years, died of an acute intracerebral hemorrhage, and pathologically showed severe amyloid angiopathy but only rare neuritic senile plaques and neurofibrillary tangles. That she was apolipoprotein E epsilon2/3 heterozygous suggests that the epsilon2 allele may have exerted a selective protective effect resulting in late onset relatively mild Alzheimer's disease despite severe amyloid angiopathy. This family emphasizes the need for more investigation into the role of presenilin mutations in amyloid deposition, especially in the cerebral vasculature, and the role of these changes in clinical dementia.
Explore the source record for details and available documents.
In a period of social transformation, we must reinvent health care. For guidance, we can look to the evolving discipline of medical informatics and to the patterns of investment in the practice arena. A top ranked application need, the computerized patient record (CPR) offers cost savings and supports clinical quality and ambulatory care. In the new millennium, we need to define our values with precision and use technology to achieve quality health care.
Explore the source record for details and available documents.
BACKGROUND: Plasma cholesteryl ester transfer activity influences the distribution of cholesterol among plasma lipoproteins and changes in its activities may influence the response of plasma lipoprotein cholesterol levels to increased cholesterol intake in the form of eggs. OBJECTIVE: The aim of the study was to determine the effect of increased egg intake on plasma newly synthesized cholesteryl ester transfer (NCET) activity and plasma lipids and lipoprotein levels in free-living men and women. DESIGN: The study was longitudinal and included a 12 d intervention arm and a similar control period immediately prior to the intervention to account for any changes in variables with time. SUBJECTS: Thirty two healthy subjects aged 20-57 y and consuming self-selected diets were recruited. Twelve men and 14 women were entered into the intervention arm of the study. Twelve of these subjects and six others were in the control group. INTERVENTIONS: Subjects who participated in the intervention phase received one additional egg per day. RESULTS: Plasma NCET activity decreased significantly (P = 0.05) in the 26 subjects who consumed an extra egg, mainly due to a significant (P = 0.02) decrease (-13.4%) in the activity in the women. Plasma cholesterol and apolipoprotein B-containing lipoprotein cholesterol increased significantly (P < 0.05) in the intervention group and in men (P = 0.02) but not in women. Age was correlated significantly (r = 0.519, P < 0.01) with the change in plasma NCET activity in all subjects and in men (r = -0.644, P < 0.05). The decrease in plasma NCET activity was significantly (P = 0.02) less in the lowest tertile compared with other tertiles of self-reported habitual dietary cholesterol intake independent of age and gender. CONCLUSIONS: These data suggest that an increase in dietary cholesterol reduces plasma NCET activity particularly in women and older men and individuals with higher habitual intakes of cholesterol. Furthermore, a reduction in plasma NCET activity may tend to limit the increase in apoB-containing lipoprotein cholesterol in women during increased egg consumption.
1. In this study we investigated the relationship between serum leptin levels and body fat distribution in a random sample of women of widely ranging age and body mass index. Anthropometry and dual energy X-ray absorptiometry were used to measure body fat and its distribution. 2. Leptin levels (log transformed) were not significantly correlated with age, but were significantly positively correlated (P < 0.001) with most anthropometric measures except waist-to-hip circumference ratio. The strongest correlations were with total grams of body fat and percentage body fat (r = 0.68 and 0.76 respectively, P < 0.001). When corrected for percentage body fat the partial correlation coefficients for all other measures became non-significant. The correlation with truncal body fat fell significantly from 0.66 to -0.05 after correction, but the partial correlation with total body fat remained significant (P < 0.005) when grams of truncal fat were controlled for (r = 0.21). 3. These results indicate that the relationship of serum leptin to percentage body fat is the strongest, and that truncal body fat, although the most metabolically active, does not appear to have an independent association with serum leptin.
We compared the thiamine and thiamine phosphate contents in the frontal, temporal, parietal, and occipital cortex of six patients with frontal lobe degeneration of the non-Alzheimer's type (FNAD) or frontotemporal dementia with five age-, postmortem delay-, and agonal status-matched control subjects. Our results reveal a 40-50% decrease in thiamine diphosphate (TDP) in the cortex of FNAD patients, whereas thiamine monophosphate was increased 49-119%. TDP synthesizing and hydrolyzing enzymes were unaffected. The activity of citrate synthase, a mitochondrial marker enzyme, was decreased in the frontal cortex of patients with FNAD, but no correlation with TDP content was found. These results suggest that decreased contents of TDP, which is essentially mitochondrial, is a specific feature of FNAD. As TDP is an essential cofactor for oxidative metabolism and neurotransmitter synthesis, and because low thiamine status (compared with other species) is a constant feature in humans, a nearly 50% decrease in cortical TDP content may contribute significantly to the clinical symptoms observed in FNAD. This study also provides a basis for a trial of thiamine, to improve the cognitive status of the patients.