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T Harris

Publications and source records attributed to T Harris.

At least 19 recordsLinked to original sources
PubMed2006

Endogenous sex hormone levels and risk of cognitive decline in an older biracial cohort.

BACKGROUND: Older women treated with conjugated estrogens may have an increased risk of dementia, but the effect of naturally occurring sex hormones on cognition is not certain. METHODS: Bioavailable estradiol and free testosterone level were obtained from 792 (55% men, 51% black) participants. We assessed cognition with the Modified Mini-Mental State Examination (3MS), Selective Reminding Test (SRT) and CLOX 1 at baseline and 2 years later. RESULTS: Women in the lowest estradiol tertile were more likely than those in the highest tertile to decline (> or = 1.0 S.D. of change) on 3MS (25% versus 9%, adjusted odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.6-9.6) and on SRT (28% versus 12%, adjusted OR [95% CI] = 3.3 [1.4-7.9]) but not CLOX 1. There was a borderline association between low estradiol tertile and decline on SRT in men (22% versus 14%, adjusted OR [95% CI] = 1.9 [0.9-3.9]). Testosterone level was not associated with decline in cognition in either men or women. Findings did not differ by race. CONCLUSIONS: Older women with low estradiol levels were more likely to experience decline in global cognitive function and verbal memory, and a similar trend was observed for verbal memory in men. This supports the hypothesis that endogenous sex hormones may play an important role in the maintenance of cognitive function in older adults.

Age Distribution↗
PubMed2006

PPAR-gamma Pro12Ala genotype and risk of cognitive decline in elders.

BACKGROUND: The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been associated with decreased risk of diabetes and obesity, both disorders linked to cognitive impairment. We tested whether this polymorphism is associated with cognition. METHODS: Two thousand nine hundred sixty-one participants (mean age, 74.1; 41% Black; 52% women) were administered the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and 4 year follow-up. Test scores were adjusted for age, sex, education, cerebrovascular disease, depression and APOE genotype and additionally for race. We determined the association between Ala allele and development of cognitive decline (3MS decline of > or = 5 points). RESULTS: At baseline, unadjusted scores on both cognitive tests were higher for Ala carriers compared to non-carriers (3MS, 94.2 versus 92.5, p<0.001; DSST, 40.2 versus 34.5, p<0.001). Similarly, follow-up scores were higher for Ala carriers. Multivariable adjustment led to similar results; additional adjustment for race attenuated the baseline 3MS results. After 4 years, 17.5% of Ala carriers developed cognitive decline compared to 25% among non-carriers (unadjusted OR=0.61; 95%CI, 0.46-0.82; adjusted OR=0.75; 95%CI, 0.55-1.02). Further adjustment for metabolic variables including fasting blood glucose and lipid level did not change the results. CONCLUSIONS: The PPAR-gamma Ala12 allele carriers may have less risk of developing cognitive decline.

Aged↗
PubMed2006

Collagen impairs glucocorticoid actions in airway smooth muscle through integrin signalling.

BACKGROUND AND PURPOSE: Airway wall remodelling in asthma is characterised by a number of structural changes, including an increase in the volume of airway smooth muscle (ASM), and the abundance of the extracellular matrix (ECM) protein, collagen, is increased. We have investigated the mechanism of collagen-induced glucocorticoid resistance of proliferation, and migration of ASM. EXPERIMENTAL APPROACH: ASM cultured from human airways has been seeded on to either type I monomeric collagen or a laminin pentapeptide, YIGSR. The role of alpha2beta1 integrin in the collagen-induced glucocorticoid resistance was investigated using a function blocking monoclonal antibody. KEY RESULTS: Culture of ASM on collagen I, but not laminin, led to a greater proliferative response that was insensitive to regulation by dexamethasone (100 nM). The anti-migratory effects of the glucocorticoid, fluticasone propionate (1 nM) were also impaired by contact of ASM with collagen. The impaired anti-mitogenic action of dexamethasone was associated with a failure to reduce the levels of the rate-limiting cell cycle regulatory protein, cyclin D1. When signalling through the alpha2beta1 integrin was reduced, dexamethasone-mediated reductions in proliferation and cyclin D1 levels were restored. CONCLUSIONS AND IMPLICATIONS: In the collagen-rich microenvironment of the inflamed and fibrotic asthmatic airway, integrin/ECM interactions may contribute to glucocorticoid resistance.

Androstadienes↗
PubMed2006

Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and body composition study.

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [OR(integral)] = 1.34, 95% confidence interval [CI] 1.10-1.63; OR(trabecular )= 1.25, 95% CI 1.02-1.53; OR(cortical )= 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.

Aged↗
PubMed2006

Lack of association between chondrocalcinosis and increased risk of cartilage loss in knees with osteoarthritis: results of two prospective longitudinal magnetic resonance imaging studies.

OBJECTIVE: To evaluate the relationship between chondrocalcinosis and the progression of knee osteoarthritis (OA) using longitudinal magnetic resonance imaging (MRI) assessments. METHODS: Longitudinal knee MRIs were obtained in the Boston OA Knee Study (BOKS) and in the Health, Aging and Body Composition (Health ABC) Study. Chondrocalcinosis was determined as present or absent on baseline knee radiographs. Cartilage morphology was graded on paired longitudinal MRIs using the Whole-Organ Magnetic Resonance Imaging Score in 5 cartilage subregions of each of the medial and lateral tibiofemoral joints. Cartilage loss in a subregion was defined as an increase in the cartilage score of > or = 1 (0-4 scale). The risk for change in the number of subregions with cartilage loss was assessed using Poisson regression, with generalized estimating equations to account for correlations. Analyses were adjusted for age, sex, body mass index, baseline cartilage score, and presence of damaged menisci. RESULTS: In BOKS, 23 of the 265 included knees (9%) had chondrocalcinosis. In Health ABC, 373 knees were included, of which 69 knees (18.5%) had chondrocalcinosis. In BOKS, knees with chondrocalcinosis had a lower risk of cartilage loss compared with knees without chondrocalcinosis (adjusted risk ratio [RR] 0.4, 95% confidence interval [95% CI] 0.2-0.7) (P = 0.002), and there was no difference in risk in Health ABC (adjusted RR 0.9, 95% CI 0.6-1.5) (P = 0.7). Stratification by intact versus damaged menisci produced similar results within each cohort. CONCLUSION: In knees with OA, the presence of chondrocalcinosis was not associated with increased cartilage loss. These findings do not support the hypothesis that chondrocalcinosis worsens OA progression.

Aged↗
PubMed2006

CNS tuberculosis: a longitudinal analysis of epidemiological and clinical features.

In a prospective Canadian cohort of 82 764 patients with tuberculosis (TB), the risk of developing central nervous system manifestations of TB (CNS-TB) (1%) was higher among younger, female, Aboriginal and foreign-born persons (P < 0.005), together with an elevated mortality risk (RR 4.23), compared to controls with only pulmonary TB. TB detection was lower in the CNS-TB group (P < 0.005), while the likelihood of being cured was also reduced (P < 0.005). CNS-TB remains a serious complication of TB in the industrialised world.

Adolescent↗
PubMed2005

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects.

BACKGROUND: Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. METHODS: The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70-79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD). RESULTS: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H(2)O v 74.2 cm H(2)O, p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p<0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV(1)) was associated with IL-6 (adjusted regression coefficients (beta) = -5.3 (95% CI -9.1 to-1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to -1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8 (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. CONCLUSIONS: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV(1), quadriceps strength, and exercise capacity.

Aged↗
PubMed2005

Size-controlled synthesis and characterization of thiol-stabilized gold nanoparticles.

Size-controlled synthesis of nanoparticles of less than a few nanometers in size is a challenge due to the spatial resolution limit of most scattering and imaging techniques used for their structural characterization. We present the self-consistent analysis of the extended x-ray absorption fine-structure (EXAFS) spectroscopy data of ligand-stabilized metal nanoclusters. Our method employs the coordination number truncation and the surface-tension models in order to measure the average diameter and analyze the structure of the nanoparticles. EXAFS analysis was performed on the two series of dodecanethiol-stabilized gold nanoparticles prepared by one-phase and two-phase syntheses where the only control parameter was the gold/thiol ratio xi, varied between 6:1 and 1:6. The two-phase synthesis resulted in the smaller particles whose size decreased monotonically and stabilized at 16 A when xi was lowered below 1:1. This behavior is consistent with the theoretically predicted thermodynamic limit obtained previously in the framework of the spherical drop model of Au nanoparticles.

Journal Article↗
PubMed2005

London bombings July 2005: the immediate pre-hospital medical response.

On July 7th 2005 a series of terrorist bombs exploded in London. The transport system was targeted and at least 54 passengers were killed and around 700 injured. This paper describes the immediate pre-hospital medical response to the four scenes. From the perspective of the London Helicopter Emergency Medical Service the deployment, difficulties on scene and the initial lessons learned are discussed.

Blast Injuries↗
PubMed2005

When should we thrombolyse patients with pulmonary embolism? A systematic review of the literature.

The early mortality in pulmonary embolism (PE) is largely predicted by the associated cardiovascular response, with progressive right ventricular failure, hypotension, shock, and circulatory arrest being associated with increasing mortality. Thrombolysis may improve the prognosis of PE associated with these varying degrees of circulatory collapse, but has no place in the treatment of small emboli with no cardiovascular compromise, as it carries a significant risk of haemorrhage. This review sets out to guide the emergency physician in deciding which patients with PE may benefit from thrombolysis.

Anticoagulants↗
PubMed2005

Animal transport and welfare: a global challenge.

Animal welfare has moved on from being a concern of a caring few to the stuff of international legislation. The author argues that more research is needed into animal welfare, especially since legislation should be based on sound science rather than emotion or anthropomorphism. The farming and animal handling community should consider the potential benefits of animal welfare rather than viewing the whole issue as a threat. The animal welfare community can assist both animals and themselves by stressing the economic advantages to be obtained from better animal welfare. Better welfare requires more than just being kind to animals, but a combination of skills, science and experience that need to be combined into one overall effective discipline.

Animal Welfare↗
PubMed2004

The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex.

BACKGROUND: The aetiology of the learning difficulty in tuberous sclerosis is debated. It may be related to the amount of tubers in the brain or caused by the infantile spasms that occur in early life. AIMS: To examine the relative contributions to final intelligence (IQ) made by both cerebral tubers and infantile spasms. METHODS: As part of an epidemiological study of tuberous sclerosis in the south of England, patients were recruited who were able to undergo magnetic resonance imaging (MRI) without the need for an anaesthetic. Epilepsy history was determined by interview and review of clinical records. IQ was assessed using either Wechsler intelligence scales or Raven's matrices. RESULTS: A total of 41 patients consented to have an MRI scan. IQ scores were normally distributed about a mean of 91. Twenty six patients had a positive history of epilepsy, and 11 had suffered from infantile spasms. There was a significant relation between the number of tubers and IQ. Infantile spasm status partly confounded the relation between tubers and IQ, but did not render the relation statistically insignificant. The relation between infantile spasms and learning difficulty remained strong even when controlling for the number of tubers.

Adolescent↗
PubMed2003

Inflammatory markers and cognition in well-functioning African-American and white elders.

BACKGROUND: Several lines of evidence suggest that inflammatory mechanisms contribute to AD. OBJECTIVE: To examine whether several markers of inflammation are associated with cognitive decline in African-American and white well-functioning elders. METHODS: The authors studied 3,031 African-American and white men and women (mean age 74 years) enrolled in the Health, Aging, and Body Composition Study. Serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) and plasma levels of tumor necrosis factor-alpha (TNFalpha) were measured at baseline; cognition was assessed with the Modified Mini-Mental State Examination (3MS) at baseline and at follow-up. Cognitive decline was defined as a decline of >5 points. RESULTS: In age-adjusted analyses, participants in the highest tertile of IL-6 or CRP performed nearly 2 points lower (worse) on baseline and follow-up 3MS (p < 0.001 for all) and declined by almost 1 point over the >2 years (p = 0.01 for IL-6 and p = 0.04 for CRP) compared with those in the lowest tertile. After multivariate adjustment, 3MS scores among participants in the highest tertile of IL-6 and CRP were similar at baseline but remained significantly lower at follow-up (p < or = 0.05 for both). Those in the highest inflammatory marker tertile were also more likely to have cognitive decline compared with the lowest tertile for IL-6 (26 vs 20%; age-adjusted odds ratio [OR] = 1.34; 95% CI 1.06 to 1.69) and for CRP (24 vs 19%; OR = 1.41; 95% CI 1.10 to 1.79) but not for TNFalpha (23 vs 21%; OR = 1.12; 95% CI 0.88 to 1.43). There was no significant interaction between race and inflammatory marker or between nonsteroidal anti-inflammatory drug use and inflammatory marker on cognition. CONCLUSIONS: Serum markers of inflammation, especially IL-6 and CRP, are prospectively associated with cognitive decline in well-functioning elders. These findings support the hypothesis that inflammation contributes to cognitive decline in the elderly.

Black or African American↗
PubMed2003

Aging bone in men and women: beyond changes in bone mineral density.

Using peripheral quantitative computed tomography (pQCT) we assessed trabecular and cortical bone density, mass and geometric distribution at the tibia level in 512 men and 693 women, age range 20-102 years, randomly selected from the population living in the Chianti area, Tuscany, Italy. Total, trabecular and cortical bone density decreased linearly with age ( p<0.0001 in both sexes), and the slope of age-associated decline was steeper in women than in men. In men, the cortical bone area was similar in different age groups, while in women older than 60 years it was significantly smaller by approximately 1% per year. The total cross-sectional area of the bone became progressively wider with age, but the magnitude of the age-associated increment was significantly higher in men than in women ( p<0.001). The minimum moment of inertia, an index of mechanical resistance to bending, remained stable with age in men, while it was significantly lower in older compared with younger women (0.5% per year). The increase in bone cross-sectional area in aging men may contribute to the maintenance of adequate bone mechanical competence in the face of declining bone density. In women this compensatory mechanism appears to be less efficient and, accordingly, the bone mechanical competence declines with age. The geometric adaptation of increasing cross-sectional bone size is an important component in the assessment of bone mechanical resistance which is completely overlooked, and potentially misinterpreted, by traditional planar densitometry.

Adult↗
PubMed2003

Evaluating a model of caregiving for people with psychosis.

BACKGROUND: The caregiving experience has been conceptualised as distress or satisfaction attributed to various factors in the carer's external and internal world. AIMS: The aim of this study was to test how such factors relate to one another in the framework of a 'stress-coping' model using data from a group of carers of people with psychosis. METHOD: Standard univariate analyses and graphical modelling techniques were applied to baseline and follow-up interview data available from a clinical trial of a support package offered to 77 carers in contact with a community psychiatric service. RESULTS: Results at baseline were consistent with a stress-coping model. Carer distress was most strongly associated with coping. In turn, coping was associated with two sets of factors - one related to appraisal and caregiving difficulty, the other to social support. Using a small sample of longitudinal data (n = 38), most individual measures were predictable from baseline. However, there was again a strong association between carer distress and current coping. Support from confidants assumed an important relationship to effective coping. The level of effective coping increased over time while caregiving difficulty decreased, but carer appraisal and distress did not change. CONCLUSIONS: The findings provide some support for an interactive, stress-coping model of caregiving in psychosis. Effective coping in caregivers may improve with support from confidants. Carer distress may not change while caregiving continues.

Adaptation, Psychological↗
PubMed2003

An exploratory randomised controlled trial of a support programme for carers of patients with a psychosis.

BACKGROUND: Despite an acknowledgement of the impact of serious mental disorders on informal caregivers, we still know little about how to best help them. The aim of the study was to evaluate the effectiveness of a two-phased carers' intervention comprising family sessions followed by relatives' groups. This intervention was designed to be of 'intermediate' intensity, that is,one lying between brief educational programmes and long-term family psychoeducational treatments. METHODS: An exploratory randomised controlled trial was conducted comparing the experimental support programme with 'standard' care. All carers of patients with a psychotic disorder from a defined population were approached. Outcome measures were based on a 'stress-appraisal-coping' model of caregiving. RESULTS: Despite concerted attempts to engage carers, only 42% participated in the study. The carers' programme did not offer any significant advantage on any of the outcome measures: psychological morbidity, negative appraisal, coping or social support. The severity of caregiving difficulties decreased over the study period for the group as a whole. CONCLUSIONS: There is still uncertainty about the most effective interventions for carers. Meeting 'needs' may not improve caregiver distress.

Adaptation, Psychological↗
PubMed2003

Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex.

BACKGROUND: Intellectual impairments are a recognized feature of tuberous sclerosis complex (TSC), but the frequency and degree of intellectual impairments has not been systematically studied in large epidemiological samples using standardized measures. As such, the form of the IQ distribution (uni- or bi-modal) has not been established and the relationship between IQ and other features (e.g. epilepsy history) is poorly delineated. To address these shortcomings, we assessed the intellectual abilities of a large epidemiological sample of individuals with TSC, drawn from the 'Wessex' area of SW England and compared them with the abilities of their unaffected siblings. METHOD: Standardized tests were used to estimate the abilities of 108 (56 males, 52 females, median age = 25, range = 4-75) individuals with TSC and 29 unaffected siblings (14 males, 15 females, median age = 18, range = 6-55). Seizure history was obtained from informants and medical records. RESULTS: Estimated IQ was bi-modally distributed: 55.5% had an IQ in the normal range; 14% had mild to severe impairments: and 30.5% had profound disability (IQ < 21). Forty-four per cent of the individuals with TSC had an IQ < 70. In the subset of normally intelligent individuals with TSC, IQ was normally distributed with a mean of 93.6. This mean was significantly lower than the mean IQ of unaffected siblings (IQ = 105.6). All individuals with learning disability had a history of seizures that usually commenced before 12 months of age and that often presented as infantile spasms. Multivariate analyses indicated that a history of seizures as well as a history of infantile spasms was predictive of the degree of intellectual impairment. CONCLUSIONS: Intellectual abilities were bi-modally distributed in a representative sample of individuals with TSC. The likelihood of impairment was associated with a history of seizures, particularly infantile spasms. The genetic and brain basis of these findings requires further investigation.

Adolescent↗