Case-control study of venous thromboembolism risk in users of hormone replacement therapy.
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Adult↗
Biomedical subjects
E Daly
Publications and source records attributed to E Daly.
Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging.
BACKGROUND: There are significant age and sex effects in cognitive ability and brain disease. However, sex differences in aging of human brain areas associated with nonreproductive behavior have not been extensively studied. We hypothesized that there would be significant sex differences in aging of brain areas that subserve speech, visuospatial, and memory function. METHODS: We investigated sex differences in the effect of aging on human brain morphometry by means of volumetric magnetic resonance imaging and on regional cerebral metabolism for glucose by positron emission tomography. In the magnetic resonance imaging study, we examined 69 healthy right-handed subjects (34 women and 35 men), divided into young (age range, 20 to 35 years) and old (60 to 85 years) groups. In the positron emission tomography study, we investigated 120 healthy right-handed subjects (65 women and 55 men) aged 21 to 91 years. RESULTS: In the magnetic resonance imaging study, age-related volume loss was significantly greater in men than women in whole brain and frontal and temporal lobes, whereas it was greater in women than men in hippocampus and parietal lobes. In the positron emission tomography study, significant sex differences existed in the effect of age on regional brain metabolism, and asymmetry of metabolism, in the temporal and parietal lobes, Broca's area, thalamus, and hippocampus. CONCLUSIONS: We found significant sex differences in aging of brain areas that are essential to higher cognitive functioning. Thus, our findings may explain some of the age-sex differences in human cognition and response to brain injury and disease.
Adult↗
Hormone replacement therapy in a risk-benefit perspective.
The relative cost-effectiveness of different treatment strategies for hormone replacement therapy (HRT) was assessed within the framework of a computer model. Where data were lacking, it was necessary to make assumptions about the effects of HRT, particularly in relation to combined oestrogen-progestogen therapy and cardiovascular disease; however, sensitivity analyses were performed to assess the impact of changing these assumptions on the cost-effectiveness equation. It appears that net expenditure by the NHS will depend critically on the direct costs of treatment, rather than on any indirect costs incurred or saved as a result of side-effects. In terms of mortality, a reduction in cardiovascular disease risk would have greatest impact and would overshadow any small increase in breast cancer risk which may be associated with long-term use. If the cardioprotective effect of oestrogen is real, our results suggest that long-term prophylactic treatment of hysterectomised women would be relatively cost-effective. Treatment of symptomatic menopausal women for any period of time appears to offer very good value for money. The lack of data relating to combined oestrogen-progestogen therapy and cardioprotection, and the major importance of the latter in the equation of benefits and risks, make it more difficult to draw conclusions about the cost-effectiveness of treating non-hysterectomised asymptomatic women for prophylactic reasons.
Aged↗
Observations of the low Earth orbit radiation environment from Mir.
Recent measurements of the high-energy charged particle environment with the Radiation Environment Monitor (REM) aboard the Russian Mir space station are presented. Ionizing dose rates in a silicon detector have been measured with two shieldings. The dose is mainly accumulated in two distinct areas, the South Atlantic Anomaly (SAA) and the region of closest approach to the magnetic poles. Whereas the radiation in the South Atlantic Anomaly varied little during 1995, large changes of the daily absorbed doses in the polar regions are observed. A comparison of REM doses with the NASA AP-8 and AE-8 radiation models revealed major differences. AP-8 tends to underestimate the average REM doses, whereas AE-8 overestimates REM doses, and rather describes the worst case.
Aluminum↗
Quantification of thyrotropin-releasing hormone changes and serotonin content changes following graded spinal cord injury.
Thyrotropin-releasing hormone (TRH) and serotonin (5-HT) are well known as neurotransmitters of descending bulbo-spinal tracts. 5-HT uptake caudal to (5-HT decreased) graded spinal lesions has been measured in rats and dogs and significantly correlated with the degree of cord injury. We studied 5-HT content via high-pressure liquid chromatography and radioimmunoassay measurements of TRH in dog spinal cord, both rostral and caudal, to 6 week T6 spinal transection (T) (n = 7) or T6 hemisections (H) (n = 7). Sham controls (n = 7) were used. Mean 5-HT content values were (pmole/mg): rostral sham 1.25 +/- 0.02, caudal sham 1.35 +/- 0.17, rostral T 2.65 +/- 0.36, caudal T 0.19 +/- 0.06, rostral H 2.1 +/- 0.22, and caudal H 1.0 +/- 0.31. A significant decrease in 5-HT caudal to transection versus control (P < 0.001) was seen. A trend for decreased 5-HT caudal to hemisection versus control (P < 0.1) was also seen. Mean TRH levels (pg/mg protein) were: rostral sham 40.02 +/- 18.47, caudal sham 30.61 +/- 10.03, brainstem sham 18.9 +/- 5.13, rostral T 52.4 +/- 21.34, caudal T 3.52 +/- 1.87, brainstem T 19.25 +/- 4.11, rostral H 43.45 +/- 18.61, caudal H 14.24 +/- 5.7, and brainstem H 21.89 +/- 1.23. Significant decreases for caudal TRH transection versus controls (P < 0.001) and for caudal TRH hemisection versus controls (P < 0.02) were seen. A significant difference between caudal hemisection and caudal transection TRH levels (P < 0.001) was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Hormone replacement therapy: characteristics of users and non-users in a British general practice cohort identified through computerised prescribing records.
STUDY OBJECTIVE: To assess the feasibility of recruiting a cohort of women, including long term users of postmenopausal hormone replacement therapy (HRT), through computerised general practice prescribing records, and to compare clinical and demographic characteristics of users and non-user controls. DESIGN: Cross sectional analysis of questionnaire data. SETTING: Subjects were recruited through 17 general practices in the Oxfordshire, south west Thames, and north west Thames regions that contributed to the VAMP Research Database. PARTICIPANTS: A total of 2964 women aged 45-64 years were identified. Altogether 1482 were long term (> 1 year) users of HRT and 1482 were non-user controls: 1037 (70%) of the users and 819 (55.3%) of the controls agreed to participate and provided questionnaire data. MAIN RESULTS: Users of HRT were more likely to have undergone hysterectomy than controls. Most women with a history of hysterectomy used unopposed oestrogen, while those with intact uteri generally used a combination of oestrogen and a progestagen. Among women who had undergone hysterectomy, HRT users did not differ significantly from controls over a range of demographic and clinical characteristics but they were more likely to be past users of oral contraceptives. Among women with intact uteri, users were similar to controls in terms of reported clinical characteristics, but were of higher social class and were more likely to be past users of oral contraceptives and to have had a mammogram after the age of 50. Compared with the general population, all categories of women recruited to the study were of higher social class and exhibited more health conscious behaviours. CONCLUSIONS: Electronic general practice prescribing records provide a feasible and efficient method for recruiting women to a cohort of HRT. Women who agreed to participate in this study were not representative of the general population, emphasising the importance of internal controls in such a study. Among participants, HRT users who had not undergone hysterectomy showed evidence of better health than non-users on some dimensions. In the whole sample, however, there were no appreciable differences in social class and self reported health indicators between users and controls.
Cohort Studies↗
The effects of sex steroids, and the X chromosome, on female brain function: a study of the neuropsychology of adult Turner syndrome.
Sex steroids and the X chromosome can independently affect cognitive abilities. Because subjects with Turner syndrome (TS) have gonadal aplasia, and various alterations in X chromosome structure and number, they provide a model to study the effects of sex steroids and of the X chromosome on human brain function. We used neuropsychological tests to study the cognitive abilities of 18 TS adults and 19 age/sex matched healthy controls. Nine TS subjects were mosaic for the 45,X karyotype, and 9 were non-mosaic 45,X (full TS). The TS group as a whole, compared to controls, had (i) significantly lower scores in tests of language and visual-spatial function, attention and memory, and (ii) a significantly greater discrepancy between verbal and performance scores. Mosaic TS subjects were intermediate between full TS and controls in some tests of verbal ability, but did not differ significantly from controls in others. Visuospatial ability was significantly lower than controls in both mosaic and full TS. Within the mosaic TS group, there was a significant negative correlation between visuospatial ability and % lymphocytes having a 45,X karyotype. Memory test scores were reduced independently of "X chromosome dosage" in all TS subjects. We conclude that in humans, the X chromosome is involved in development of both cerebral hemispheres, but moreso of the association neocortices. Also, sex steroids may modulate this effect--particularly in hippocampus.
Adolescent↗
The incorporation of n-3 polyunsaturated fatty acids into plasma lipid and lipoprotein fractions in the postprandial phase in healthy volunteers.
OBJECTIVE: To examine the movement of long-chain polyunsaturated n-3 fatty acids across plasma lipoprotein fractions in the postprandial phase. DESIGN: Eight healthy volunteers ingested a test meal (% energy: protein 11, carbohydrate 16, fat 73) after an overnight fast where fish oil provided the sole fat source. Blood samples were taken at baseline and at hourly intervals thereafter for 12 h. Blood lipoprotein fractions were separated and analysed for triacylglycerol fatty acid compositions. These were also determined in non-esterified fatty acid and phospholipid fractions. RESULTS: All n-3 polyunsaturated fatty acids accumulated in all plasma lipoprotein fractions and in non-esterified fatty acids. The ratios of concentrations of docosahexaenoic acid (DHA) to eicosahexaenoic acid (EHA) were higher in chylomicrons (1.4 +/- 0.4) than in very low density lipoproteins (0.9 +/- 0.5) and particularly higher than in the non-esterified fatty acid fractions (0.8 +/- 0.4). The level of eicosapentaenoic acid (EPA) rose significantly in plasma phospholipids while that of docosahexaenoic acid (DHA) did not. CONCLUSIONS: All n-3 polyunsaturated fatty acids are rapidly incorporated into all plasma lipid fractions with the exception of uptake of DHA into plasma phospholipids. There is a clear tendency for EPA and DHA to partition differently into the different plasma lipid fractions.
Adult↗
X-chromosome effects on female brain: a magnetic resonance imaging study of Turner's syndrome.
Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD12] vs 118 [13], p < 0.0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p < 0.001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,X TS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres.
Adult↗
Volumetric magnetic resonance imaging in men with dementia of the Alzheimer type: correlations with disease severity.
Using magnetic resonance imaging (MRI), we measured the volumes of various brain structures and cerebrospinal fluid (CSF) in 19 men with dementia of the Alzheimer type (DAT) and 18 healthy age-matched control men. The mean (+/- S.D) Mini-Mental State exam score (MMSE) of the DAT men was 16 +/- 7; 9 were mildly (MMSE > 20), 5 moderately (MMSE 10-20), and 5 severely (MMSE < 10) demented. Brain and CSF volumes were normalized as a percent of the traced intracranial volume to control for the relation of volumes of cerebral structures to head size, and analyzed statistically. The whole group of DAT subjects had significantly smaller mean cerebral brain matter and temporal lobe volumes (p < 0.05), and significantly larger mean ventricular and temporal lobe peripheral CSF volumes than did controls. Mean volumes of the subcortical nuclei did not differ significantly between groups, and mean volume of temporal lobe brain matter decreased significantly more than whole brain, suggesting regional loss of brain matter in DAT. Mildly demented DAT patients had significantly smaller mean cerebral brain matter and temporal lobe volumes and significantly larger volumes of lateral ventricles, and of temporal lobe peripheral CSF, than did controls. Neuropsychological measures of disease severity in DAT patients were significantly (p < 0.05) and appropriately correlated to volumes of cerebral brain matter and right lateral ventricle. These results suggest that in DAT: (i) significant brain atrophy is present early in the disease process, (ii) brain atrophy correlates with severity of cognitive impairment, and (iii) there is greater involvement of the telencephalic association system than whole brain, and there is relative sparing of the caudate, lenticular and thalamic nuclei.
Aged↗
Measuring the impact of menopausal symptoms on quality of life.
OBJECTIVE: To examine the impact of menopausal symptoms on the overall quality of life of women. DESIGN: Data collection with a questionnaire administered by an interviewer, incorporating two different quality of life measurement techniques (time trade off and rating scale). SETTING: Specialist menopause clinic and two general practices in Oxford. SUBJECTS: 63 women aged 45-60 years recruited opportunistically during a clinic or appointment with a general practitioner; no exclusion criteria. RESULTS: Subjects gave very low quality of life ratings for health states with menopausal symptoms. The time trade off method of measuring preferences for these health states (on a scale from 0 to 1, where preference for full health is given as 1) yielded utility values of 0.64 for severe menopausal symptoms and 0.85 for mild symptoms. The rating scale measurement technique yielded even lower values: utilities of 0.30 and 0.65 were obtained for severe and mild symptoms respectively. Kappa scores indicated that the two methods produced results that were poorly related but not contradictory. Comparison of quality of life ratings before and after treatment with hormone replacement therapy showed significant improvements: with the rating scale measurement technique mean increases in utility values after the relief of severe and mild menopausal symptoms were 0.56 and 0.18 respectively. CONCLUSIONS: Quality of life may be severely compromised in women with menopausal symptoms, and perceived improvements in quality of life in users of hormone replacement therapy seem to be substantial. This emphasises the need to include quality of life measurements when assessing outcomes of hormone replacement therapy. Several limitations may exist with widely applied measurement techniques, calling for the development of appropriate and well validated instruments for measuring quality of life associated with reduced health states.
Data Collection↗
HRT: an analysis of benefits, risks and costs.
A cost-effectiveness analysis of hormone replacement therapy (HRT) was undertaken to assess the relative benefits of different treatment strategies, and to identify which factors most influence cost-effectiveness. The current lack of conclusive evidence on the effects of HRT, especially in relation to combined therapy and cardiovascular disease, necessitated the use of a large number of assumptions in our model. In terms of net health benefits, the potential reduction in cardiovascular disease would have greatest impact, and would overshadow any small increase in breast cancer risk possibly associated with long-term use. Net expenditure by the NHS will depend critically on the direct costs of treatment, rather than on any indirect costs incurred or averted as a result of side-effects. In terms of cost-effectiveness, long-term prophylactic treatment of hysterectomised women and treatment of symptomatic women with a uterus compare favourably with other accepted health care interventions.
Breast Neoplasms↗
Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer's disease.
Monoamine metabolites, biopterin, acetylcholinesterase (AChE) activity, and somatostatin-like immunoreactivity (SLI) were determined in the lumbar cerebrospinal fluid (CSF) of 24 patients with dementia of the Alzheimer type (DAT) without myoclonus or extrapyramidal signs, in 8 patients with DAT and myoclonus, and in 14 age-matched healthy control subjects. In patients with DAT with myoclonus as compared with both DAT patients without myoclonus and control subjects, the concentrations of homovanillic acid and biopterin were significantly decreased. 5-Hydroxyindoleacetic acid was significantly lower in patients with myoclonic DAT as compared to patients with nonmyoclonic DAT, but not significantly lower than in control subjects. CSF AChE and SLI were significantly reduced in patients with DAT with or without myoclonus, as compared with control subjects, but AChE and SLI were not significantly different between dementia groups. These results suggest that DAT patients with myoclonus represent a distinct clinical and neurochemical DAT subtype.
Acetylcholinesterase↗
Cerebrospinal fluid monoamine markers are decreased in dementia of the Alzheimer type with extrapyramidal features.
We measured monoamine metabolites and biopterin in the CSF of 37 patients with dementia of the Alzheimer type (DAT), with or without extrapyramidal signs, and in 14 age-matched healthy controls. Compared with concentrations in DAT and controls, the concentrations of homovanillic acid (HVA) and biopterin were significantly decreased in DAT with extrapyramidal signs (EDAT). CSF 3-methoxy-4-hydroxy-phenethyleneglycol and 5-hydroxyindoleacetic acid did not differ significantly among these groups. Age at onset of dementia was positively correlated with CSF HVA (r = 0.49, p less than 0.05). The two dementia groups did not differ significantly in the extent of ventricular dilation as measured by quantitative CT, but EDAT patients had lower Mini-Mental State Examination scores than did DAT patients. When patients were matched for age and dementia severity, CSF HVA and biopterin concentrations remained significantly lower in EDAT than in DAT patients. These results indicate that EDAT patients form a distinct subgroup of DAT with evidence of central monoamine dysfunction.
Aged↗
Treatment of a post-traumatic headache.
After fantasy work in a trance state a patient with post-traumatic headaches experienced some relief as other symptoms appeared, and then total relief along with the disappearance of the other symptoms. He was able to withdraw from all medications.
Behavior Therapy↗
Social work and primary medical care.
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Comprehensive Health Care↗
Interconversion of glycine and serine in a synaptosome fraction isolated from the spinal cord, medulla oblongata, telencephalon, and cerebellum of the rat.
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Alanine↗