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Biomedical subjects

E Daly

Publications and source records attributed to E Daly.

At least 19 recordsLinked to original sources
PubMed2006

The "Americanisation" of migrants: evidence for the contribution of ethnicity, social deprivation, lifestyle and life-course processes to the mid-20th century Coronary Heart Disease epidemic in the US.

We investigated the contribution of the large-scale immigration of White Europeans into the US between 1850 and 1930 to the timing and extent of the epidemic pattern of heart disease between 1900 and 1980. The analyses are based on data collected through the United States Federal Census from 1850 to the present. The hardcopy historical record confirms that census reports themselves and related monographs were concerned from 1850 with excessive mortality from heart disease of immigrants, particularly of Northern European origin and initially at least, their first-generation native-born children. Our analysis of the electronic database indicates a strong relationship between the percentage of US population foreign born and native born of foreign parentage and age adjusted mortality from heart disease. We identified a lag of 50 years giving the maximum linear correlation coefficient for men (r(2) = 0.92), and for women a shorter lag of 38 years and an earlier decline in Coronary Heart Disease (CHD) rates (r(2) = 0.96). Both the rise and fall of the CHD epidemic over an 80-year period correspond closely to the rise and fall of the foreign population in previous years. For the foreign born only, age adjusted negative binomial general estimated equation (GEE) models calculate the relative risk of dying of heart disease per 10% increase in proportion foreign born. There is an independent influence for men until 1930 and for women throughout the period from 1910 onwards. We conclude there is an impact of immigration on the pattern of the epidemic, mediated through a combination of factors, such as accumulated life-course susceptibility, deprived socio-economic conditions upon arrival, and the enthusiastic uptake of behaviours related to the classic risk factors of smoking, high saturated fat and salt diet. Our analysis provides a more contextualised understanding of the scale and timing of the epidemic of CHD in the US.

Censuses↗
PubMed2003

Effects of long-term estrogen replacement therapy on growth hormone response to pyridostigmine in healthy postmenopausal women.

OBJECTIVE: There is growing evidence that estrogen may protect against age-related cognitive decline and reduce the risk of developing Alzheimer's disease (AD) in healthy, postmenopausal women. The underlying biological basis for this is not known but may include preservation of cholinergic systems. Cholinergic dysfunction has been implicated in the aetiology of age-related memory impairment and AD. We studied the effect of prolonged use of estrogen replacement therapy (ERT) on central cholinergic tone in healthy postmenopausal women. METHOD: Growth hormone (GH) responses to oral pyridostigmine (120 mg) were measured over a 3 h period in thirty healthy postmenopausal women, 15 on long-term ERT and 15 ERT naïve. RESULTS: GH release following pyridostigmine was significantly larger in ERT treated women than in ERT naïve women. In addition within the ERT treated group there was a significant positive correlation between duration of estrogen treatment and GH response. CONCLUSIONS: Long-term ERT can enhance cholinergic function in postmenopausal women and this may be related to duration of estrogen treatment. Modulation of central cholinergic function may be one mechanism by which long-term ERT could preserve cognitive function in healthy, postmenopausal women.

Aged↗
PubMed2002

Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis.

Hormone replacement therapy (HRT) increases the risk of venous thrombosis. We investigated whether this risk is affected by carriership of hereditary prothrombotic abnormalities. Therefore, we determined the two most common prothrombotic mutations, factor V Leiden and prothrombin 20210A in women who participated in a case-control study on venous thrombosis. Relative risks were expressed as odds ratios (OR) with 95% confidence intervals (CI95). Among 77 women aged 45-64 years with a first venous thrombosis, 51% were receiving HRT at the time of thrombosis, compared with 24% of control women (OR = 3.3, CI95 1.8-5.8). Among the patients, 23% had a prothrombotic defect, versus 7% among the control women (OR = 3.8, CI95 1.7-8.5). Women who had factor V Leiden and used HRT had a 15-fold increased risk (OR = 15.5, CI95 3.1-77), which exceeded the expected joint odds ratio of 6.1 (under an additive model). We conclude that the thrombotic risk of HRT may particularly affect women with prothrombotic mutations. Efforts to avoid HRT in women with increased risk of thrombosis are advisable.

Case-Control Studies↗
PubMed2001

Effects of estrogen replacement therapy on human brain aging: an in vivo 1H MRS study.

Estrogen replacement therapy (ERT) may preserve cognitive function in postmenopausal women, but the mechanism is unknown. Thus, the authors studied aging of parietal lobe and hippocampus using proton MR spectroscopy. ERT naïve postmenopausal women had a significant increase in choline-containing compounds (Cho) compared to long-term ERT users and young women. Cho reflects increased neuronal/glial membrane turnover. Thus, ERT's "neuroprotective" effect may include modulating the effects of age on neural integrity in brain regions involved in cognitive function.

Adult↗
PubMed2001

Prolactin response to d-fenfluramine in postmenopausal women on and off ERT: comparison with young women.

Estrogen is thought to have an impact on both psychological well being and cognitive function. The biological basis to this is not fully understood, but may involve estrogen's interactions with central serotonergic (5-HT) systems. Therefore, we studied the effect of long-term estrogen hormone replacement therapy (ERT) on central 5-HT tone in healthy postmenopausal women and made comparisons with young women. Prolactin (PRL) responses to the specific 5-HT releasing and re-uptake inhibiting agent, d-fenfluramine, were measured in three groups of healthy women: 11 young, 11 postmenopausal on long-term ERT, and 11 postmenopausal ERT naïve. PRL responses were significantly decreased in ERT naïve women compared to young healthy women. In contrast, PRL responses were not different between estrogen-treated and young women. Overall, there was a significant relationship between older age and lower PRL responsivity. These results suggest that central 5-HT tone is reduced in healthy postmenopausal women who are ERT naïve, but not in postmenopausal women who have received prolonged estrogen treatment. Estrogen may modulate age-related changes in 5-HT tone. This may partly explain why estrogen can decrease vulnerability to mood disorders and cognitive changes in postmenopausal women.

Adult↗
PubMed2001

Structural brain abnormalities associated with deletion at chromosome 22q11: quantitative neuroimaging study of adults with velo-cardio-facial syndrome.

BACKGROUND: Velo-cardio-facial syndrome (VCFS) is associated with deletions in the qll band of chromosome 22, learning disability and psychosis, but the neurobiological basis is poorly understood. AIMS: To investigate brain anatomy in adults with VCFS. METHOD: Magnetic resonance imaging was used to study 10 patients with VCFS and 13 matched controls. We carried out three analyses: qualitative; traced regional brain volume; and measurement of grey and white matter volume. RESULTS: The subjects with VCFS had: a high prevalence of white matter hyperintensities and abnormalities of the septum pellucidum; a significantly smaller volume of cerebellum; and widespread differences in white matter bilaterally and regional specific differences in grey matter in the left cerebellum, insula, and frontal and right temporal lobes. CONCLUSIONS: Deletion at chromosome 22q11 is associated with brain abnormalities that are most likely neurodevelopmental and may partially explain the high prevalence of learning disability and psychiatric disorder in VCFS.

Adult↗
PubMed2001

Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression.

Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability. A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability. Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls. After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory. The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.

Adult↗
PubMed2001

Proton Irradiation Facility and space radiation monitoring at the Paul Scherrer Institute.

The Proton Irradiation Facility (PIF) has been designed and constructed, in cooperation between Paul Scherrer Institute (PSI) and European Space Agency (ESA), for terrestrial proton testing of components and materials for spacecraft. Emphasis has been given to generating realistic proton spectra encountered by space-flights at any potential orbit. The facility, designed in a user-friendly manner, can be readily adapted to the individual requirements of experimenters. It is available for general use serving also in testing of radiation monitors and for proton experiments in different scientific disciplines. The Radiation Environment Monitor REM has been developed for measurements of the spacecraft radiation conditions. Two instruments were launched into space, one into a Geo-stationary Transfer Orbit on board of the STRV-1b satellite and one into a Low Earth Orbit on the Russian MIR station. The next generation of monitors (SREMs--Standard REMs) is currently under development in partnership of ESA, PSI and Contraves-Space. They will operate both as minimum intrusive monitors, which provide radiation housekeeping data and alert the spacecraft when the radiation level crosses allowed limits and as small scientific devices measuring particle spectra and fluxes. Future missions as e.g. INTEGRAL, STRV-1c and PROBA will be equipped with new SREMs.

Atlantic Ocean↗
PubMed2000

Predicting conversion to Alzheimer disease using standardized clinical information.

OBJECTIVE: To identify aspects of a standardized clinical assessment that can predict which individuals within the category of "questionable" Alzheimer disease (AD) have a high likelihood of converting to AD over time. DESIGN: Detailed semistructured interviews were performed at baseline and annually for 3 years. SETTING: University-based gerontology research program. PATIENTS: The patient population consisted of 165 individuals 65 years and older: 42 of the participants had a Clinical Dementia Rating (CDR) of normal cognition (CDR rating, 0.0) and 123 had a rating of questionable AD (CDR rating, 0.5). After 3 years of follow-up, 23 of the 123 subjects with questionable AD were diagnosed with probable AD. MAIN OUTCOME MEASURES: The interview was used to generate a summary measure based on the sum of 6 CDR categories, known as the Total Box Score. The responses to 32 selected questions from the interview also were examined. RESULTS: Likelihood of progression to AD during the follow-up period was strongly related to the Total Box Score. For example, more than 50% of individuals with a Total Box Score of 2.0 or higher at baseline developed AD during the follow-up interval, whereas about 10% of individuals with a Total Box Score of 1.0 or lower developed AD during this same period. Selected questions from the standardized clinical interview also were highly predictive of subsequent conversion to AD among the study population. Eight selected questions from the clinical interview at baseline, combined with the CDR Total Box Score, identified 88.6% of such individuals accurately (questionable group, 82/91; converter group, 19/23). CONCLUSIONS: A standardized clinical assessment can be used to identify the subgroup of individuals within the category of questionable AD who have a high likelihood of converting to AD over time. Subjects who met the criteria for questionable AD had a variety of trajectories during a 3-year follow-up, suggesting that diverse factors may influence the functional changes observed in this population.

Aged↗
PubMed2000

Explicit and implicit neural mechanisms for processing of social information from facial expressions: a functional magnetic resonance imaging study.

The processing of changing nonverbal social signals such as facial expressions is poorly understood, and it is unknown if different pathways are activated during effortful (explicit), compared to implicit, processing of facial expressions. Thus we used fMRI to determine which brain areas subserve processing of high-valence expressions and if distinct brain areas are activated when facial expressions are processed explicitly or implicitly. Nine healthy volunteers were scanned (1.5T GE Signa with ANMR, TE/TR 40/3,000 ms) during two similar experiments in which blocks of mixed happy and angry facial expressions ("on" condition) were alternated with blocks of neutral faces (control "off" condition). Experiment 1 examined explicit processing of expressions by requiring subjects to attend to, and judge, facial expression. Experiment 2 examined implicit processing of expressions by requiring subjects to attend to, and judge, facial gender, which was counterbalanced in both experimental conditions. Processing of facial expressions significantly increased regional blood oxygenation level-dependent (BOLD) activity in fusiform and middle temporal gyri, hippocampus, amygdalohippocampal junction, and pulvinar nucleus. Explicit processing evoked significantly more activity in temporal lobe cortex than implicit processing, whereas implicit processing evoked significantly greater activity in amygdala region. Mixed high-valence facial expressions are processed within temporal lobe visual cortex, thalamus, and amygdalohippocampal complex. Also, neural substrates for explicit and implicit processing of facial expressions are dissociable: explicit processing activates temporal lobe cortex, whereas implicit processing activates amygdala region. Our findings confirm a neuroanatomical dissociation between conscious and unconscious processing of emotional information.

Adult↗
PubMed2000

Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years. Relationships to hormone replacement therapy.

Hormone replacement therapy (HRT) has been shown to increase the relative risk of idiopathic venous thromboembolism (VTE) about threefold in several observational studies and one randomised controlled trial. Whether or not this relative risk is higher in women with underlying thrombophilia phenotypes, such as activated protein C (APC) resistance, is unknown. We therefore restudied the participants in a case-control study of the relationship between the use of HRT and the occurrence of idiopathic VTE in women aged 45-64 years. After protocol exclusions, 66 of the cases in the original study and 163 of the controls were studied. Twenty haematological variables relevant to risk of VTE were analysed, including thrombotic states defined from the literature. The relative risk of VTE showed significant associations with APC resistance (OR 4.06; 95% CI 1.62, 10.21); low antithrombin (3.33; 1.15, 9.65) or protein C (2.93; 1.06, 8.14); and high coagulation factor IX (2.34; 1.26, 4.35), or fibrin D-dimer (3.84; 1.99, 7.42). HRT use increased the risk of VTE in women without any of these thrombotic states (OR 4.09; 95% CI 1.26, 13.30). A similar effect of HRT use on the relative risk of VTE was also found in women with prothrombotic states. Thus for example, the combination of HRT use and APC resistance increased the risk of VTE about 13-fold compared with women of similar age without either APC resistance or HRT use (OR 13.27; 95% CI 4.30, 40.97). We conclude that the combination of HRT use and thrombophilias (especially if multiple) increases the relative risk of VTE substantially; hence women known to have thrombophilias (especially if multiple) should be counselled about this increased risk prior to prescription of HRT. However, HRT increases the risk of VTE about fourfold even in women without any thrombotic abnormalities: possible causes are discussed.

Activated Protein C Resistance↗
PubMed1999

Hormone replacement therapy: patterns of use studied through British general practice computerized records.

OBJECTIVE: We aimed to describe the longitudinal pattern of hormone replacement therapy (HRT) consumption in a cohort of long-term users (defined as use for >1 year). METHOD: We carried out longitudinal analysis of prescription data derived from GPs' computer records. Subjects were recruited through 15 general practices in the former Oxford, South West and North West Thames Regions that contributed to the VAMP/OPCS general practice research database. All women in the practices aged 45-64 years in September 1991 were identified. Of these, the analysis concerned the 1224 long-term users and 1154 non-user controls who remained in the practices from September 1991 to March 1995; 868 (71%) of the users and 698 (61%) of the controls also provided questionnaire data. RESULTS: The prevalence of HRT use was 15% in 1992, a rise of 16% from 1991. The prevalence of long-term use was 10%; 22% of the cohort identified as taking HRT between April and September 1991 had left the practices or were not taking HRT 1 year later. But for the group defined as long-term users in 1992, the rate of discontinuation was less than 5% per year over the following 2 1/2 years. Users of opposed therapy were 50% more likely to discontinue than users of unopposed therapy. Almost all women who had or had not undergone hysterectomy were taking unopposed or opposed therapy, respectively. Over 80% of prescriptions were for oral therapy. A third of users of either opposed or unopposed therapy changed the formulation during the 4 years of observation, and two-thirds of those who used both forms changed at least once in addition. Two changes were required to accommodate 94% of users. CONCLUSIONS: Once women have taken HRT for a year, their continuation rate is over 95% per annum. Although the majority of women stayed with one formulation, a substantial minority changed formulation quite frequently, three formulations being required to accommodate 94% of long-term users over 4 years. Any trial of HRT use will need to recruit long-term users and allow for change in formulation of HRT in its protocol.

Aged↗
PubMed1998

REM measurements aboard MIR during 1995.

Measurements of the South Atlantic Anomaly (SAA) made with the Radiation Environment Monitor (REM) aboard Mir from November 1994 to February 1996 are presented. During this period an increase of the SAA radiation by approximately 25% is observed, which coincides with a lowering of the radio solar flux. Radio solar flux is one of the parameters controlling the earth's atmospheric distribution and with it the absorption of inner radiation belt protons forming the SAA. Due to the altitude gradient of the atmospheric density, the proton fluxes in the SAA are anisotropic (loss cone, east-west effect). The measured distribution can be accounted for by basic models.

Anisotropy↗
PubMed1997

A PET study of Turner's syndrome: effects of sex steroids and the X chromosome on brain.

Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.

Adult↗
PubMed1996

Risk of venous thromboembolism in users of hormone replacement therapy.

BACKGROUND: The association between current use of oral contraceptives and increased risk of venous thromboembolism (VTE) has been firmly established. Although data-sheets for hormone replacement therapy (HRT) carry similar warnings as regards VTE, evidence of an association is inconclusive. We carried out a hospital-based case-control study to investigate whether current use of HRT is associated with VTE. METHODS: We screened all women aged 45-64 years admitted to hospitals in the area of the Oxford Regional Health Authority with a suspected diagnosis of VTE between February, 1993, and December, 1994. We recruited 81 cases of idiopathic VTE and 146 hospital controls with disorders of eyes, skin, ears, respiratory and alimentary tracts, kidneys, bones, and joints, and trauma; controls were matched to cases for age-group and date and district of admission. To increase the study power, an additional 22 cases of idiopathic VTE and 32 hospital controls admitted before February, 1993, were recruited retrospectively. Participants were questioned about medical and gynaecological history, use of oral contraceptives and HRT, use of other drugs within the previous 3 months, and lifestyle and socioeconomic characteristics. Detailed diagnostic data were extracted from the notes of eligible cases. Matched analyses, adjusted for body-mass Index, socioeconomic group, and history of varicose veins, were undertaken by conditional logistic regression. FINDINGS: 44 (42.7%) cases and 44 (24.7%) controls were current users of HRT. The adjusted odds ratio for VTE in current users of HRT compared with non-users (never-users and past users combined) was 3.5 (95% CI 1.8-7.0; p < 0.001). No association was found with past use, and risk appeared to be highest among short-term current users (adjusted likelihood ratio test of trend in odds ratios across different durations of current use, p = 0.011). INTERPRETATION: Current HRT use is associated with risk of VTE. The increased risk may be concentrated in new users. The number of extra cases appears to be only about one in 5000 users per year. These findings need to be weighed against the probable benefits of long-term treatment, including reductions in risks of osteoporotic fracture and coronary heart disease, and the probable modest increase in risk of breast cancer.

Body Mass Index↗