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Biomedical subjects

G E Smith

Publications and source records attributed to G E Smith.

At least 37 records · Page 2Linked to original sources
PubMed2003

Neuropathology of cognitively normal elderly.

Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage <IV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques. Many subjects had moderate or frequent diffuse plaques (n = 19, 49%). By the National Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met criteria for high "likelihood" of AD. Four met NIA-RI criteria for intermediate "likelihood." Seven cases met CERAD criteria for possible AD. Nineteen met Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small, old infarcts were common, but no subjects had more than 2 of these and none had a single large infarction. Thus, the majority of individuals who are cognitively normal near the time of their death have minimal amounts of tau-positive neuritic pathology (Braak stage <IV and neuritic plaques <6 per x100 field in the most affected neocortical region). The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly.

Aged↗
PubMed2002

Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia.

OBJECTIVES: To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD. METHODS: An unselected series of 67 individuals participating in the Mayo Alzheimer's Disease Research Center/Alzheimer's Disease Patient Registry who had undergone a standardized antemortem MRI study and also postmortem examination were identified. Hippocampal volumes were measured from antemortem MRI. Each postmortem specimen was assigned a pathologic diagnosis and in addition, the severity of AD pathology was staged using the method of Braak and Braak. RESULTS: Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangle--only degeneration usually had substantial hippocampal atrophy, while those with changes of typical aging did not. Among all 67 subjects, correlations (all p < 0.001) were observed between hippocampal volume and Braak and Braak stage (r = -0.39), between hippocampal volume and Mini-Mental State Examination (MMSE) score (r = 0.60), and between MMSE score and Braak and Braak stage (r = -0.41). CONCLUSIONS: Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [r = -0.63, p = 0.001]) and consequent cognitive status.

Aged↗
PubMed2002

The impact of sporadic campylobacter and salmonella infection on health and health related behaviour: a case control study.

The aim of the work was to explore the impact on general and psychological health of those with a proven bacterial gastrointestinal infection and to compare this with controls from whom no bacterial pathogen was identified. A case control study was conducted using an interviewer-administered questionnaire. Thirty-nine cases from whose faeces salmonella or campylobacter had been cultured were compared with matched controls. Reported gastrointestinal symptoms, general health and self-reported hygiene practices were compared. At the time of acute illness the General Household Questionnaire suggested similar levels of morbidity, though by follow up the controls were substantially more likely to be distressed. Cases were more likely to have changed their food preparation practices, to avoid certain eating places and to have been given advice about food preparation. In this small study a positive diagnosis of salmonella or campylobacter seems to have had a reassuring effect when compared with those for whom no diagnosis was made.

Acute Disease↗
PubMed2002

Impact of infections on primary care--greater than expected.

Though infection has declined as a cause of death it consumes a major proportion of primary care resources, and because of antibiotic resistance is increasingly important. We examined the burden of illness attributable to infection in primary care by analysing data from the fourth practice-based national morbidity survey which monitored all consultations by diagnosis in 470,000 persons over a 12 month period from September 1991 to August 1992. Rates of persons consulting, new episodes of illness and consultations were calculated according to the list of infections published by Wilson and Bhopal (W&B list), and as amended by the Communicable Disease Surveillance Centre (CDSC list); selected comparisons were made with national data on hospital derived finished consultant episodes and deaths. Forty-one percent of all registered persons consulted on at least one occasion during the year for infection (estimated by either list). Infections accounted for 40% of all new episodes of illness and 29% of all consultations; respiratory infections accounted for approximately half the infection total. New episode rates were highest in children aged less than 1 year and lowest in males 25-54 years and females 55-64 years. Except in infancy, rates were higher in females. There were 734 episodes of infection annually per 1,000 population reported in general practice compared with 20 per 1,000 finished consultant episodes. The average episode of infection prompted 1.2 general practice consultations. Improved management through more precise diagnosis by near patient tests is desirable, but is unlikely to be obtained cost effectively if consultation numbers or the time spent is substantially increased. These results emphasise the importance of adequate training for general practitioners in the natural history, epidemiology, diagnosis and treatment (pharmacology) of infection.

Adolescent↗
PubMed2002

Use of NHS Direct calls for surveillance of influenza--a second year's experience.

A second year's call data to NHS Direct are presented to evaluate their usefulness for influenza surveillance. During the winter of 2000-01, age-group-specific data relating to the 'cold/flu' algorithm were collected from six NHS Direct sites (population coverage: 16 million). The total number of calls was collected from all 23 NHS Direct sites on a daily basis. Despite the winter of 2000-01 having been a season of low activity for influenza in the United Kingdom, NHS Direct data demonstrated a peak in the 'cold/flu' calls as a proportion of the total calls (3.1% [672 'cold/flu' calls] during week 06/01). This coincided with the peak recorded by routine influenza surveillance systems. There was also an earlier peak in the proportion of 'cold/flu' calls (3.3% during weeks 52/00 [789 'cold/flu' calls] and 01/01 [749 'cold/flu' calls]) which may have been due to other respiratory infections, the lack of specificity of the definition of NHS Direct 'cold/flu' calls and an increase in 'out-of-hours' calls to NHS Direct at the time. Despite limitations, the timeliness of NHS Direct data, the total population coverage of the service and the ability to provide local information on 'cold/flu' calls make the call data suitable for further surveillance during the winter of 2001-02. It is hoped that as NHS Direct reaches a 'steady state' in terms of population coverage and uniformity of clinical support systems, it will be possible to begin to construct 'baselines' for the respiratory disease related call data.

Adolescent↗
PubMed2001

Prospective analysis of risk factors for nursing home placement of dementia patients.

OBJECTIVE: To examine risk factors for nursing home placement in a community-based dementia cohort. METHODS: Cognitively normal participants and cognitively impaired patients from a large AD Patient Registry were followed from diagnosis to placement, death, or last follow-up. This included over 3,600 person-years of surveillance. The normal group included 473 participants who did not, at any point, meet Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised (DSM-III-R) criteria for dementia. The patient group included 512 patients who met DSM-III-R criteria for dementia or criteria for mild cognitive impairment at diagnosis. Demographic, medical, social, cognitive, behavioral, and functional predictors of time to placement were examined using Cox modeling. RESULTS: In the normal group, only 21 people (4%) required nursing home placement. With subjects, enrollment year, age at initial evaluation, being widowed, and living in a retirement community were associated with time to placement in separate univariate analyses. Of 512 cognitively impaired patients, 203 (39.6%) were placed in nursing homes. Median time from diagnosis to placement was 5.3 years. Within the patient sample, four predictors were determined to be associated with time to nursing home placement. These included gender, enrollment year, functional status, and cognitive score. Interactions were present for functional status with cognitive score and enrollment year. CONCLUSION: In patients with dementia who are within 5 years of diagnosis, placement rates of approximately 10% per year can be expected. Disease severity indices including degree of cognitive and functional impairment are primary risk factors for placement.

Activities of Daily Living↗
PubMed2001

T3-activation of the rat growth hormone gene is inhibited by a zinc finger/homeodomain protein.

Since the transcription factor Zfhep is expressed in somatotropes and binds the rat growth hormone (rGH) gene T3-response element (TRE), we investigated whether Zfhep regulates the response of this gene to T3. In cotransfection experiments, Zfhep did not regulate the native rGH promoter in the absence of T3. However, Zfhep repressed T3-mediated activation significantly in either GH(3) or JEG-3 cells. Up to 70% repression was mediated through the rGH TRE in a heterologous promoter (thymidine kinase), but was not observed with the idealized DR4 or chicken lysozyme F2 TREs. Zfhep apparently does not repress T3-mediated activation simply by competition for binding to DNA since the C-terminal DNA-binding domain of Zfhep (which is sufficient for DNA-binding) is not sufficient for repression and since cotransfection of excess thyroid hormone receptor (TR) did not prevent repression by Zfhep. These data indicate that the rGH TRE is a composite element that can integrate Zfhep and T3 regulation.

Animals↗
PubMed2001

Reduction in mortality from heartwater in cattle, sheep and goats exposed to field challenge using an inactivated vaccine.

Inactivated vaccines for heartwater prepared with the commercially acceptable Montanide ISA 50 (ISA 50) adjuvant were field tested in Boer goats in Botswana, Angora goats in South Africa, and Merino sheep in Zambia and Zimbabwe. Two vaccines, one made using the Zimbabwean Mbizi isolate and the other using the respective local field isolate (Sunnyside in Botswana; Bathurst in South Africa; Lutale in Zambia), were tested at each site, except in Zimbabwe where only the Mbizi vaccine was tested. Compared with unvaccinated animals, the Mbizi vaccine significantly protected goats and sheep against field Amblyomma tick challenge in Botswana, Zambia and Zimbabwe (P = 0.018, 0.002 and 0.017, respectively), but failed to protect Angora goats in South Africa. However, in South Africa the vaccine prepared using the local field isolate Bathurst, induced significant protection (P=0.008). The vaccines containing the local isolates at all other sites were less protective than the Mbizi vaccine. The Mbizi inactivated vaccine also significantly protected 17 of 21 cattle (P = 0.05) against heartwater challenge from field ticks in Zimbabwe. Against the same challenge only 7 of 21 unvaccinated control cattle survived. This study demonstrates that heartwater is a major constraint to upgrading livestock in endemic areas, and caused an overall mortality of 77.6% in naive sheep and goats (97 of 125 died) and 67% in cattle (14 of 21 died). In contrast, the vaccine had a protective effect by reducing the overall mortality in sheep and goats to 54.3% (113 of 208 died) and to 19% in cattle (4 of 21 died).

Africa South of the Sahara↗
PubMed2001

Results of follow-up of human contacts of bovine tuberculosis in cattle during 1993-7 in North Staffordshire.

The purpose of the study was to describe the results of follow up of human contacts of bovine tuberculosis. The bovine tuberculosis cases occurred on farms in North Staffordshire between 1993 and 1997. A total of 162 people were identified as having close contact with cattle diagnosed as having bovine tuberculosis, or who had drunk unpasteurized milk from a herd with bovine tuberculosis. A retrospective review of chest clinic notes was performed. One hundred and thirty-eight people attended for follow up, and Heaf test results, necessity for chest X-ray and further clinical follow-up are described. No case of human Mycobacterium bovis infection was identified. It is suggested that follow-up of human contacts is limited to those with close contact with herds who have bovine tuberculosis and cattle with visible pulmonary lesions or evidence of udder infection. Children on the farms with affected cattle should also be offered BCG in advance of the routine school's programme.

Adolescent↗
PubMed2001

Understanding the diagnostic capabilities of cognitive tests.

Statistics (i.e., sensitivity, specificity, hit rates, positive and negative predictive values, odds ratios, and likelihood ratios) that best describe a diagnostic test's ability to classify persons as either "impaired" or "normal," but that are not commonly reported in neuropsychological research, are reviewed. These statistics are applied to Mayo Cognitive Factor Scale scores (MCFS; Smith et al., 1994) to demonstrate information that can be acquired about the diagnostic capabilities of cognitive tests as they are commonly used in clinical settings. Multivariate analyses then generated a statistical model that combines MCFS scores and improves on the diagnostic capabilities of the individual MCFS scores. This model enjoys better diagnostic power than individual scores. It establishes that cognitive testing that uses multiple measures is very good at differentiating normal from impaired cognitive states. Information is also provided that helps clinicians quantify a person's risk for cognitive impairment based on specific cognitive test score(s).

Aged↗
PubMed2001

Mild cognitive impairment and Alzheimer disease: regional diffusivity of water.

PURPOSE: To compare the regional diffusivity of water in the brains of normally aging elderly people and patients with mild cognitive impairment (MCI) or Alzheimer disease. MATERIALS AND METHODS: Magnetic resonance images were obtained in 21 patients with Alzheimer disease, 19 patients with MCI, and 55 normally aging elderly control subjects without evidence of cognitive impairment. Regions of interest were drawn to compare the apparent diffusion coefficient (ADC) and the anisotropy index (AI) in frontal, parietal, temporal, occipital, anterior, and posterior cingulate white matter (WM), and the thalami and hippocampi. RESULTS: Hippocampal ADC was higher in MCI and Alzheimer disease patients than in control subjects. ADC of the temporal stem and posterior cingulate, occipital, and parietal WM was higher in Alzheimer disease patients than in control subjects. Except for occipital AI, which was lower in MCI patients than in control subjects, there were no differences in AI among the three groups for any of the regions. CONCLUSION: Hippocampal ADC was significantly different between control subjects and MCI patients, many of whom likely have preclinical Alzheimer disease. Elevation in hippocampal ADC may reflect early ultrastructural changes in the progression of Alzheimer disease.

Aged↗
PubMed2001

Assessment and management of behavioral disturbances in nursing home patients with dementia.

Behavioral disturbances among nursing home patients with dementia are common and substantially affect patients and caregivers. Assessing the environmental, medical, and psychiatric causes of problematic behaviors and implementing a plan of behavioral, medical, and psychiatric management can reduce difficult target behaviors. This article presents a multifaceted approach to assessing patients with dementia who have behavioral problems, reviews medical and pharmacological management of these problems, and presents a multidisciplinary approach to developing treatment plans aimed at reducing such behaviors among nursing home patients with dementia.

Anticonvulsants↗
PubMed2001

PHLS primary care consultation--infectious disease and primary care research and service development priorities.

In 1999 for the first time the PHLS undertook a questionnaire survey of general practitioners' views of the burden of infectious disease and the priorities for research and development of infectious disease services within the PHLS. Three hundred and seventy-one (38%) of 979 questionnaires mailed to chairs of primary care groups in England, and general practitioners in research networks, were returned. Service areas: computer transfer of laboratory results was considered of greatest priority. Guidance on antibiotic usage, guidance on infectious diseases and education for general practitioners were ranked two, three and four. Burden of infectious disease in primary care: upper respiratory tract infections, tonsillitis/pharyngitis, otitis media/externa and acute cough were placed one, three, four and seven respectively. Urinary tract infections were ranked second and dyspepsia/Helicobacter pylori fifth. Leg ulcers, diarrhoea, genital chlamydia infection and vaginal discharge were other diseases considered to cause a large burden of ill-health. Genital chlamydia, tuberculosis, Helicobacter pylori and meningococci were ranked one, two, three, and five in the NHS opportunity to affect the burden of ill-health. Priorities for improvements to diagnostic tests, evidence on which to base treatment and guidance: chronic fatigue/ME was ranked top in these areas. The other top ten syndromes ranked in order were genital chlamydia infections, antibiotic resistance surveillance, vaginal discharge, leg ulcers, sinusitis, otitis media/externa, dyspepsia/Helicobacter pylori, Creutzfeld Jacob Disease, and tonsillitis. This consultation exercise has highlighted broad areas for future PHLS involvement in primary care. In order to make progress, further consultation is needed with groups of GPs, and other relevant bodies. Particularly for the areas ranked in the top ten, the type of further PHLS involvement needs to be defined. For some syndromes (chronic fatigue and leg ulcers) this may be writing guidance and for others (respiratory tract infections) more treatment trials are required. The purposes and possible methods of communicable disease surveillance in general practice should be the subject of additional consultation.

Attitude of Health Personnel↗
PubMed2001

Can calls to NHS Direct be used for syndromic surveillance?

This study assessed whether NHS Direct could be a useful source of surveillance data for communicable diseases, using influenza as a pilot condition. Data on the weekly total number of calls and the number from people reporting influenza-like symptoms to three pilot NHS Direct sites were collected between November 1999 and March 2000. NHS Direct data were compared with routinely available influenza surveillance data. The NHS Direct call rate peaked at 331 per 100,000 population in week 52 of 1999. The percentage of calls for 'influenza-like illness' (one site) peaked at 15% during week 51. Information about weekly call numbers to NHS Direct could be produced in a timely way. It was not clear whether the observed peak in calls reflected a true increase in influenza or whether it was the result of an increase in calls over the Christmas/Millennium holiday period due to more difficulty in accessing other services. The ability to assess the proportion of calls made directly by, or on behalf of, each age group will be of vital importance in interpreting seasonal respiratory disease.

Disease Outbreaks↗
PubMed2000

Rates of hippocampal atrophy correlate with change in clinical status in aging and AD.

BACKGROUND: The cognitive continuum in the elderly population can be conceptually divided into those who are functioning normally (control subjects), those with a mild cognitive impairment (MCI), and those with probable AD. OBJECTIVES: To test the hypothesis that the annualized rates of hippocampal atrophy differ as a function of both baseline and change in clinical group membership (control, MCI, or AD). METHODS: The authors identified 129 subjects from the Mayo Clinic AD Research Center/AD Patient Registry who met established criteria for normal control subjects, MCI, or probable AD, both at entry and at the time of a subsequent clinical follow-up evaluation 3 +/- 1 years later. Each subject underwent an MRI examination of the head at the time of the initial assessment and at follow-up clinical assessment; the annualized percentage change in hippocampal volume was computed. Subjects who were classified as controls or patients with MCI at baseline could either remain cognitively stable or could decline to a lower functioning group over the period of observation. RESULTS: The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MC > control. Within the control and MCI groups, those who declined had a significantly greater rate of volume loss than those who remained clinically stable. The mean annualized rates of hippocampal atrophy by follow-up clinical group were: control-stable 1.73%, control-decliner 2.81%, MCI-stable 2.55%, MCI-decliner 3.69%, AD 3. 5%. CONCLUSION: Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD.

Aged↗
PubMed2000

Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: A 1H MRS study.

BACKGROUND: Mild cognitive impairment (MCI) is a recently described transitional clinical state between normal aging and AD. Assuming that amnestic MCI patients had pathologic changes corresponding to an early phase and probable AD patients to a later phase of the disease progression, the authors could approximate the temporal course of proton MR spectroscopic (1H MRS) alterations in AD with a cross-sectional sampling scheme. METHODS: The authors compared 1H MRS findings in the superior temporal lobe, posterior cingulate gyri, and medial occipital lobe in 21 patients with MCI, 21 patients with probable AD, and 63 elderly controls. These areas are known to be involved at different neurofibrillary pathologic stages of AD. RESULTS: The N-acetylaspartate (NAA)/creatine (Cr) ratios were significantly lower in AD patients compared to both MCI and normal control subjects in the left superior temporal and the posterior cingulate volumes of interest (VOI) and there were no between-group differences in the medial occipital VOI. Myoinositol (MI)/Cr ratios measured from the posterior cingulate VOI were significantly higher in both MCI and AD patients than controls. The choline (Cho)/Cr ratios measured from the posterior cingulate VOI were higher in AD patients compared to both MCI and control subjects. CONCLUSION: These findings suggest that the initial 1H MRS change in the pathologic progression of AD is an increase in MI/Cr. A decrease in NAA/Cr and an increase in Cho/Cr develop later in the disease course.

Aged↗