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Biomedical subjects

M Prince

Publications and source records attributed to M Prince.

At least 19 recordsLinked to original sources

Viral IL-10 gene transfer decreases inflammation and cell adhesion molecule expression in a rat model of venous thrombosis.

Post-thrombotic inflammation probably contributes to chronic venous insufficiency, and little effective treatment exists. IL-10 is an anti-inflammatory cytokine that previously has been shown to decrease perithrombotic inflammation and thrombosis. We investigated in a rat model whether local expression of viral IL-10 (vIL-10) in a segment of vein that undergoes thrombosis would confer an anti-inflammatory effect and how this effect might be mediated. Rats underwent inferior vena cava isolation, cannulation, and instillation of saline or adenovirus encoding either beta-galactosidase or vIL-10. Two days after transfection, thrombosis was induced, 2 days after this the rats underwent gadolinium (Gd)-enhanced magnetic resonance venography exam, and the vein segments were harvested. Tissue transfection was confirmed by either RT-PCR of vIL-10 or positive 5-bromo-4-chloro-3-indolyl beta-d-galactopyranoside (X-Gal) staining. vIL-10 significantly decreased both leukocyte vein wall extravasation and area of Gd enhancement compared with those in controls, suggesting decreased inflammation. Immunohistochemistry demonstrated decreased endothelial border staining of P- and E-selectin, while ELISA of vein tissue homogenates revealed significantly decreased P- and E-selectin and ICAM-1 levels in the vIL-10 group compared with those in controls. Importantly, native cellular IL-10 was not significantly different between the groups. However, neither clot weight nor coagulation indexes, including tissue factor activity, tissue factor Ag, or von Willebrand factor levels, were significantly affected by local vIL-10 expression. These data suggest that local transfection of vIL-10 decreases venous thrombosis-associated inflammation and cell adhesion molecule expression, but does not directly affect local procoagulant activity.

Animals↗

The association between APOE and dementia does not seem to be mediated by vascular factors.

OBJECTIVE: The effect of APOE on dementia may be mediated through dyslipidemia and atherogenesis through its effect on cholesterol metabolism. The authors investigated this possibility among aged survivors from the UK Medical Research Council Trial of the Treatment of Hypertension in Older Adults. DESIGN: A total of 370 of 657 survivors from an initial cohort of 1,088 recruited into the trial between 1983 and 1985 were traced in 1994 and agreed to be screened for dementia. Blood samples were analyzed for APOE genotype and serum fibrinogen. Cholesterol level, smoking behavior, blood pressure, body mass index, and EKG recordings had been measured at recruitment 10 to 12 years earlier. Odds ratios (ORs) for the association between APOE epsilon4/* and both AD and dementia were estimated and adjusted incrementally for the effect of age and premorbid intelligence, cholesterol, other risk factors for vascular disease, and EKG evidence of cardiovascular disease. RESULTS: The authors diagnosed 24 cases of National Institute of Neurological and Communicative Disorders and Stroke AD from 41 cases of dementia. The crude OR for the association between APOE epsilon4/* and AD was 3.40 (95% CI 1.30 to 8.91). APOE genotype was associated with serum cholesterol level, and there was a nonsignificant trend for an association with smoking behavior. After adjusting for these and all other vascular risk factors and vascular disease variables listed earlier, the OR for the association between APOE epsilon4/* and AD increased to 4.81 (1.60 to 14.4). CONCLUSION: Presence of APOE epsilon4/* seems to increase the risk for dementia and AD independently of its effect on dyslipidemia and atherogenesis.

Aged↗

Dementia in developing countries. A consensus statement from the 10/66 Dementia Research Group.

Less than one-tenth of all population-based research into dementia is directed towards the two-thirds or more of cases living in developing parts of the world. The 10/66 Dementia Research Group has been formed to redress this imbalance, encouraging active research collaboration between centres in different developing countries and between developed and developing countries. The 10/66 group consisted initially of researchers attending a symposium on dementia research in developing countries, held at the 1998 Alzheimer's Disease International conference. They noted a growing interest in this area, with many active researchers and others wishing to start new studies. There was felt to be an urgent need for more research: quantifying prevalence and incidence, exploring regional variations in international collaborations using harmonized methodologies, describing care arrangements for people with dementia, quantifying the impact on caregivers and evaluating the effectiveness of any newly implemented services. Methodological problems need to be addressed, particularly development of culture- and education-fair dementia diagnostic procedures. Good-quality research can generate awareness, pioneer service development and influence policy.

Cost of Illness↗

Methodological issues for population-based research into dementia in developing countries. A position paper from the 10/66 Dementia Research Group.

The 10/66 Dementia Research Group has been formed to promote good-quality, internationally comparable research into dementia in developing countries through active research collaboration. In this position paper, we review existing research into dementia prevalence in developing regions of the world. Seven methodologically robust studies were identified. The prevalence of dementia, age-adjusted to the age structure of the Kerala population, ranged from 1.3% to 5.3% for all those aged 60 or over and from 1.7% to 5.2% for all those aged 65 and over. Two studies, from Ibadan, Nigeria and Ballabgarh, India, reported strikingly low prevalence figures. The reported prevalence for most studies was somewhat lower than the consistent figures for Europe reported by the EURODEM concerted action. Based on critical review of the literature, and on the practical research experience of members of the 10/66 group, recommendations have been made for procedure in the following areas: age limits for inclusion in dementia surveys, age ascertainment, sampling, scope for incidence studies, functional assessment and culture- and education-fair dementia diagnosis.

Age Distribution↗

A pilot study of sibling resemblance in later life.

OBJECTIVE: Behavioural genetic studies of later life are strictly limited. We carried out a community-based pilot study of sibling resemblance with the primary aims of establishing the feasibility of such work in this population and estimating genetic influence on depression and its risk factors. METHODOLOGY: Data were collected on surviving siblings of individuals interviewed in previous phases of an epidemiological study of the elderly (the Gospel Oak survey); scales relevant to the investigation of late life depression and its risk factors were utilized. Since families tend to be geographically scattered, the interview was conducted by telephone. Comparisons were made between data relating to the siblings and those obtained on the probands. Variability in phenotypic traits and environmental measures was partitioned into between- and within-family variation, in order to distinguish familial and non-familial sources of variation. Intraclass correlations were used to estimate the strength of genetic influences on continuous measures, while pairwise concordances were calculated for dichotomous traits. RESULTS: Thirty-two siblings from 20 families were ultimately identified and interviewed. Intraclass correlations for the Depression and Dementia Diagnostic Scales and the Handicap Scale were 0, 0.27 and 0.22, respectively. Those for number of life events, number of friends in contact and number of neighbours in contact were 0.08, 0.03 and 0, respectively. Concordance for both depression caseness and dementia caseness was 0. DISCUSSION: There were difficulties carrying out this study, which are discussed. The study is the first of its kind to examine familial resemblance for the common disorders of old age. Establishing ways of engaging elderly families with research will be a challenge that future research will need to meet.

Aged↗

Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats.

Tinospora cordifolia is widely used in Indian Ayurvedic medicine for treating diabetes mellitus. Oral administration of an aqueous T. cordifolia root extract (TCREt) to alloxan diabetic rats caused a significant reduction in blood glucose and brain lipids. The extract caused an increase in body weight, total haemoglobin and hepatic hexokinase. The root extract also lowers hepatic glucose-6-phosphatase and serum acid phosphatase, alkaline phosphatase, and lactate dehydrogenase in diabetic rats. Thus TCREt has hypoglycaemic and hypolipidaemic effect.

Animals↗

Smoking, drinking, and incident cognitive impairment: a cohort community based study included in the Gospel Oak project.

OBJECTIVES: Recent longitudinal studies have reported that smoking increases risk for cognitive impairment and that moderate alcohol intake could be preventive. The association between both cigarette smoking and alcohol drinking and incident cognitive impairment was studied in a representative population. METHODS: This is a 1 year prospective population based cohort study of all residents aged 65 or over in the electoral ward of Gospel Oak in London, UK (n=889). Cognitive impairment was assessed at baseline and 1 year later using the organic brain syndrome (OBS) cognitive impairment scale from the short CARE structured assessment. Subjects who were cognitively impaired at baseline were excluded from this analysis. RESULTS: The prevalence of OBS cognitive impairment was 10.4% at index assessment and the 1 year cumulative incidence of cognitive impairment was 5.7%. Cognitive impairment was not associated with use of alcohol, although there was a non-significant association in the direction of a protective effect against onset of cognitive impairment for moderate drinkers compared with non-drinkers and heavy drinkers. Current smoking status predicted cognitive impairment (risk ratio (RR) 3.7; (95% confidence interval (95% CI)=1.1-12.3) independently from sex, age, alcohol, occupational class, education, handicap, depression, and baseline cognitive function. CONCLUSIONS: Smoking seems to be a prospective risk factor for incident cognitive impairment; thus encouragement of older people to stop smoking could be considered as part of a strategy to reduce the incidence of cognitive impairment.

Age Factors↗

Increasing rates of suicide in young men in England during the 1980s: the importance of social context.

Attempts to explain rising rates of suicide among young men in Britain and elsewhere during the 1980's have identified the characteristics of those people who kill themselves. Little, however, is known about the impact that changes in social context may have had on changing rates of suicide during this time. Changes in aggregate levels of unemployment, poverty, marriage and the proportion of adults living alone during the 1980s were derived from data collected in the UK National Census of 1981 and 1991. In an ecological analysis these changes were compared with changes in age-adjusted rates of suicide in men aged 15 to 44, in 364 county districts of England between the beginning and end of the 1980s. Areas experiencing the lowest increase in rates of suicide were those that experienced the smallest rise in the proportion of people living alone, the greatest increase in unemployment and highest levels of social deprivation. In addition to investigating the effect that characteristics of people have in determining the risk of suicide in individuals who kill themselves, further attention needs to be paid to the impact that social context may have on mediating these risks.

Adolescent↗

Vascular risk factors and Alzheimer's disease.

OBJECTIVE: We aim to summarise the recent and accumulating epidemiological research which suggests that cardiovascular disease and vascular risk factors play an important role as risk factors for Alzheimer's disease (AD) in later life. METHOD: The epidemiological literature is summarised in considering the evidence for such an association, focusing on optimally designed population-based studies. Potential mechanisms of association are considered, drawing on relevant findings from neuroscience. RESULTS: Cardiovascular disease and vascular risk disorders appear to be important factors in the aetiology of AD. However, there is a paucity of prospective studies with an adequate duration of follow-up to investigate the apparent age- and time-dependent nature of these associations. CONCLUSIONS: Vascular disorders represent potentially preventable risk factors with an important population impact due to their high prevalence in developed countries. The concept of AD and vascular dementia as clearly distinguishable disorders clinically or aetiologically is becoming increasingly tenuous. A better understanding of the relationship between AD and vascular disorders will depend on a more flexible diagnostic and conceptual framework.

Aged↗

Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene.

Isolated growth hormone (GH) deficiency (IGHD) is a rare cause of short stature. The same mutation of the gene encoding the growth hormone-releasing hormone receptor (GHRHR) has been identified as the basis for IGHD in three families from the Indian subcontinent. The prevalence and heterogeneity of defects in the GHRHR gene are not known. Twenty-two dwarf members of a large, extended kindred containing at least 105 affected members with autosomal recessive short stature underwent extensive endocrine evaluation, which confirmed markedly reduced or undetectable serum concentrations of GH that did not increase in response to different stimuli. DNA sequences of the 13 exons and intron-exon boundaries of the GHRHR gene were determined in an index patient. A novel homozygous 5' splice site mutation (G-->A at position +1) in IVS1 was found. Thirty of the affected subjects tested were homozygous for this mutation, and 64 clinically unaffected patients were either heterozygous for the mutation (n = 41, including 9 obligate carriers) or homozygous for the wild-type sequence (n = 23). We describe a novel mutation in the GHRHR gene as cause of dwarfism in the largest kindred with familial IGHD described to date.

Adolescent↗

Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa.

PURPOSE: To evaluate the degree of inner retinal preservation in the extramacular regions of postmortem retinitis pigmentosa (RP) eyes. METHODS: Eighteen RP retinas and 11 age-matched healthy retinas were sectioned for morphometric analysis by light microscopy. The 18 RP retinas were classified by disease severity and mode of inheritance. Cell nuclei in the outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL) were counted in adjacent 125-microm segments from an area spanning the region between 4 mm and 10 mm from the fovea. RESULTS: A mixed-effects model showed a decrease in mean cell counts for each of the cell layers when the severity groups and inheritance types compared with those of control retinas. There was no statistically significant difference in the number of nuclei preserved in the INL and GCL in the moderate group compared with the severe group. Results from the INL counts for the different inheritance types of RP showed a higher overall mean percentage of cells was preserved for the autosomal dominant RP (ADRP) group when compared with the X-linked (XLRP) and simplex RP groups. Analysis of the GCL counts revealed significantly more counts only in the ADRP group compared with the XLRP group; the other group comparisons were not significant. CONCLUSIONS: Retinitis pigmentosa results in cell loss in all retinal layers, with the most profound loss in the ONL, followed by the GCL and then the INL. The preservation of the INL and GCL in the extramacular region is less than that previously reported for the macular region of the same retinas.

Aged↗

The recognition and treatment of depression in older people in primary care.

OBJECTIVES: To examine general practitioners' (GP) awareness of depression in their elderly patients (aged over 65) and to identify characteristics of those patients least likely to be recognized and treated. DESIGN: A cross-sectional study comparing the clinical opinion of the GP with assessment of mental state using a validated interview schedule (the Short Comprehensive Assessment and Referral Evaluation). SETTING AND SUBJECTS: 510 elderly residents in the Gospel Oak area of Camden in North London registered with 28 GPs at 13 practices. MAIN OUTCOME MEASURES: Agreement between GP view and patients interview. Evidence of active management measured by examining GP records for appointments, referrals and prescription of psychotropic mediation. RESULTS: GPs were aware of depression in 36 (51%) of 70 depressed patients. Those least likely to be recognized were men, the married, those with high levels of physical handicap, those suffering from visual impairment and those who were least well educated. Of the 32 patients believed to be depressed, 12 (38%) were prescribed antidepressant medication and/or referred to mental health/social services. CONCLUSIONS: Levels of recognition of depression were lower than other recent reports. These findings may reflect the continued debate about the most suitable management of the elderly depressed in primary care and stress the need for further evaluation of appropriate treatment strategies for this group.

Aged↗

Associations between diagnoses, impairments, disability and handicap in a population of elderly people.

BACKGROUND: 'Handicap' is the disadvantage for an individual that results from ill-health. It represents an important outcome in chronic disabling disease, but has proved difficult to measure until recently. The strength of association between handicap and other health status measures, and the relative contributions of health and socioeconomic variables to handicap have not been studied previously. METHODS: We undertook a cross-sectional survey of all people > 65 years old in a defined geographical area of North London. The interview was based on the short-CARE psychiatric survey tool, and in addition included measures of physical health and disability, the London Handicap Scale, income, social support and housing. In all, 654 residents (74%) from a register of 889 were interviewed. A random sample of 225 had additional data collected which are reported in this analysis. RESULTS: Strength of association with handicap scores increased progressively from diagnosis to impairment to disability. Variation in handicap with diagnosis was explained by impairment, and variation with impairment was mostly explained by disability. Age, housing quality, social support and income were associated with handicap score, but confounding by these did not explain the association between handicap and other aspects of disablement. Disease-associated variables explained quantitatively much more variation in handicap than socioeconomic variables. CONCLUSIONS: The most potent influences on handicap are disease and disability, justifying the high priority given by health services to detection, treatment and rehabilitation. Where this is not possible handicap may be reduced to some extent through socioeconomic intervention.

Aged↗

Do antiarthritic drugs decrease the risk for cognitive decline? An analysis based on data from the MRC treatment trial of hypertension in older adults.

We ascertained nonsteroidal anti-inflammatory drug (NSAID) use in 2,651 participants in the UK MRC treatment trial of hypertension in older adults and measured change in cognitive function over the subsequent 54 months. There was a significant, although modest, association between change in the Paired Associate Learning Test score over time and NSAID use, which was modified by age. NSAID users showed less decline, with younger subjects seeming to benefit more than older. We found no relationship between NSAID use and time taken to complete the Trail Making Test and also no relationship between anti-indigestion drug use and either cognitive outcome. These analyses highlight the need for larger studies with prospective classification of NSAID use and adequate control of confounding, including exposure to other medications. A randomized controlled trial of NSAIDs, in those known to be at risk of cognitive decline or dementia, may be indicated in the future.

Adrenergic beta-Antagonists↗

Implementation of groups for creative expression on a psychiatric inpatient unit.

Patients benefited from creativity group participation through expression of both positive and negative feelings, group acceptance, and acceptance of self in a non-competitive activity. Psychiatric nurses can lead creativity groups with a focus on creative expression, rather than psychotherapy. No specific training in the arts is required for these simple creative formats. It was found from using a variety of creative formats that, overall, patients received group projects better than individual projects done in a group setting.

Art Therapy↗

Is chronic low-level lead exposure in early life an etiologic factor in Alzheimer's disease?

Few environmental risk factors for Alzheimer's disease have been identified. This lack of information may reflect the fact that salient factors affect most of the population in developed countries. Furthermore, the critical period of exposure may be earlier than hitherto suspected, during the first years of life, as the brain differentiates and develops. Exposure to lead at levels lower than those associated with evident toxicity causes mild intellectual impairment in childhood. I hypothesize that this may be one of the childhood exposures that also confers an additional risk for the onset of Alzheimer's disease.

Adolescent↗

Concurrent validity of a telephone-administered version of the Gospel Oak instrument (including the SHORT-CARE).

OBJECTIVE: The aim of the study was to establish the concurrent validity of a telephone-administered version of the survey measures utilized in the Gospel Oak studies, the core of which was the SHORT-CARE. DESIGN: Comparisons were made between data obtained by administering the interview in its conventional, face-to-face form with those generated by conducting it by telephone. SETTING: A UK teaching hospital. PATIENTS: Elderly subjects of both sexes, recruited from geriatric and psychogeriatric day hospitals. MEASURES: The Depression Diagnostic Scale, Dementia Diagnostic Scale and Organic Brain Syndrome scale (all taken from the SHORT-CARE) and the London Handicap Scale. RESULTS: For depressive symptomatology, cognitive impairment, subjective memory impairment and handicap, intraclass correlations were 0.86, 0.89, 0.83 and 0.70, respectively. The kappa coefficient for agreement on case-level diagnosis of pervasive depression was 0.79. CONCLUSIONS: These results indicate that the instrument is broadly reliable when administered by telephone.

Aged↗