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Biomedical subjects

G E Swan

Publications and source records attributed to G E Swan.

At least 19 recordsLinked to original sources

Toxicokinetics of cotyledoside following intravenous administration to sheep.

Cotyledoside, a bufadienolide cardiac glycoside, was administered intravenously to sheep in 2 studies. In experiment 1, sheep (n = 4) received 0.0135 mg/kg daily on 5 consecutive days and in the 2nd experiment, sheep (n = 4) received 0.027 mg/kg as a single dose. Jugular blood was collected at different time intervals and kinetic parameters were determined. The data fitted a 1-compartmental model. In both experiments a short half-life (t1/2) and mean residence time (MRT), a relative small volume of distribution (Vd(ss)) and rapid clearance were calculated. In the 1st experiment, t1/2 and MRT increased significantly (P < 0.007) from Day (D) 0 to D4. It is suggested that the rapid decline in plasma cotyledoside concentrations in sheep denotes rapid distribution of cotyledoside to the tissues or extracellular spaces and possible accumulation at the biophase.

Animals↗

Differential rates of regional brain change in callosal and ventricular size: a 4-year longitudinal MRI study of elderly men.

Brain structure changes in size with normal aging, but the rate at which different structures change is controversial. We used magnetic resonance imaging (MRI) performed twice, 4 years apart, to compare rates of age-related size change of the corpus callosum, which has been inconsistently observed to thin with age, with change in the lateral ventricles, which are well established to enlarge. Subjects were 215 community dwelling, elderly men (70-82 years old at initial MRI), who were participants in a longitudinal study of cardiovascular risk factors. Percent change in size was significant for both the callosal and ventricular measures, but annual rate of ventricular expansion (2.9%) was significantly greater than annual rate of callosal thinning (-0.9%). Callosal regions showed statistically equivalent rates of shrinkage; ventricular dilatation was symmetrical. Neither callosal and ventricular rates of change correlated with each other (r = 0.01), nor did genu and splenium rates of change correlate with each other (r = 0.05). Tests of speeded processing were administered contemporaneously with both MRIs to examine functional ramifications of observed brain changes. Decline in the Mini-Mental State Examination was related to thinning of the splenium, and decline in Stroop test word reading was selectively related to thinning of the callosal body. These longitudinal data support the contentions that differential rates of change occur in different brain regions in normal aging, age-related callosal thinning contributes to functional declines, and rate of change in one region can be independent of rate of change in another region, even within a brain structure.

Aged↗

Supply of veterinary medicinal products to an emerging farming community in the North West Province of South Africa.

A study was conducted in the Madikwe District of the North West Province to investigate the supply of veterinary medicinal products to small-scale, subsistence and emerging farmers. A combination of individual interviews, focus groups and direct observation was used to collect data. Stock remedies were made available to farmers within the district at Field Service Units that were managed by administrative staff of the Directorate of Field Services. The state veterinarian and animal health technicians were not directly involved with the sale of products. Most farmers still travelled to farmers' cooperatives in the larger centres outside the district to purchase the veterinary medicinal products they needed. Factors such as the quality of service provided, affordability and availability of required products as well as inaccessibility of outlets to all farmers contributed to the poor support of these outlets by the farmers of the district.

Animal Diseases↗

Genetic factors in self-reported snoring and excessive daytime sleepiness: a twin study.

Subjects in this study included 1,560 intact male-male twin pairs (818 monozygotic [MZ], 742 dizygotic [DZ]) of mean age (+/- SD) 74.2 +/- 2.8 yr. The Epworth Sleepiness Scale (ESS) was used to assess daytime sleepiness and standardized questionnaires assessed snoring. Multivariate genetic model fitting was used to estimate the contribution of genetic and nongenetic (environmental) influences to the variation and covariation of obesity with snoring and daytime sleepiness. In this sample, 26% were habitual snorers, 18% reported excessive daytime sleepiness (ESS > or = 11), and 29% were obese (body mass index [BMI] > or = 28). By using structural equation modeling, we estimated that genetic factors accounted for 64% of the variance in obesity, 40% of the variance in daytime sleepiness, and 23% of the variability in self-reports of snoring. We found a significant genetic correlation between obesity and snoring and between obesity and excessive daytime sleepiness (EDS), although for the most part the genetic variance in snoring and sleepiness was nonoverlapping with the genetic variance for obesity. We conclude from these data that self-reported symptoms of snoring and daytime sleepiness in older men have a genetic basis that is largely independent of genes associated with obesity.

Aged↗

Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study.

OBJECTIVE: To evaluate the relative risk (RR) of mild cognitive impairment (MCI) associated with cerebrovascular risk factors and cerebrovascular-related brain changes. DESIGN: Mild cognitive impairment was determined for the subjects of the prospective National Heart, Lung, and Blood Institute Twin Study. Quantitative measures of brain, white matter hyperintensity, cerebral infarction, apolipoprotein E genotype, and psychometric testing were obtained. RESULTS: Subjects with MCI were older (73.5 +/- 3.0 vs 72.1 +/- 2.8 years), consumed less alcohol (3.7 +/- 5.8 vs 7.0 +/- 10.7 drinks per week), had greater white matter hyperintensity volumes (0.56% +/- 0.82% vs 0.25% +/- 0.34% of cranial volume), and had an increased prevalence of apolipoprotein E4 genotype (31.4% vs 19.2%) than normal subjects. White matter hyperintensity and the presence of the apolipoprotein E4 genotype were associated with a significantly increased risk for MCI. When all subjects were included in the analysis, alcohol consumption was associated with a reduced risk for MCI (RR = 0.93, P<.05). When subjects with a history of symptomatic cerebrovascular disease were excluded from the analysis, elevated midlife diastolic blood pressure was associated with an increased risk for MCI (RR = 1.70, P<.05). CONCLUSIONS: Elevated midlife blood pressures, and the resulting increased white matter hyperintensities, increase the risk for MCI in a group of community-dwelling older men to at least the same degree as apolipoprotein E4 genotype. Given the common occurrence of elevations in midlife blood pressure, early and effective treatment may be warranted to prevent late-life brain abnormalities and MCI. Moreover, since many individuals with MCI progress to clinical dementia, longitudinal evaluations of this cohort will be important.

Aged↗

Heritability of hippocampal size in elderly twin men: equivalent influence from genes and environment.

Recent studies have established that environmental factors can modify hippocampal structure and enhance function in adult rodents, but the extent to which genes and the environment exert differential contributions to hippocampal structural integrity in humans is unknown. Here, we applied the twin model in a large sample of elderly twin men to examine in late life the balance of environmental and genetic effects on the size of the hippocampus in comparison with other brain structures. This study provides novel evidence that the volume of the hippocampus, as measured on MRI, is subject to substantially less genetic control than are comparison brain regions also measured: temporal horn volume, midsagittal area of the corpus callosum, and intracranial volume (ICV). In particular, about 60% of the temporal horn variance and 80% of the callosal and ICV variance was attributable to genetic influences, whereas only 40% of the hippocampal variance was attributable to genetic influences. These results suggest that environment, whether by itself or in interaction with genes, has the potential of exerting greater and possibly longer control in modifying hippocampal size than other brain regions that are under greater genetic control. Considering the potential of environmental modification of this structure suggested by lower heritability, the hippocampus appears well-suited to support the dynamic processes of encoding and consolidation of new, declarataive memories.

Aged↗

A genetic analysis of the Epworth Sleepiness Scale in 1560 World War II male veteran twins in the NAS-NRC Twin Registry.

Responses to the eight-item Epworth Sleepiness Scale (ESS) obtained from 1560 World War II male veteran twin pairs [818 monozygotic (MZ), 742 dizygotic (DZ)] were analysed to determine the extent to which genetic influences are involved in self-reported daytime sleepiness in the elderly. Average ESS score (+/- SD) in this sample was 7.1 +/- 3.9, range 0--24. More than half of the twins (65%--67%) reported a moderate to high chance of falling asleep while lying down to rest; fewer than 3% admitted that this would occur while sitting and talking to someone or while stopped in traffic. Daytime sleepiness was not associated with age but was significantly and positively associated with obesity. The intraclass twin correlation on ESS scores was 0.39 in MZ pairs and 0.21 in DZ pairs (both P < 0.001). Structural equation modeling of the observed variance-covariance matrices for MZ and DZ twins estimated the heritability of ESS to be 38% (95% confidence interval 33%--44%). Environmental influences not shared by twin brothers accounted for the remaining variance in daytime sleepiness. A reasonable interpretation of the heritability of ESS in this healthy cohort of elderly male twins is a genetic susceptibility for disordered breathing during sleep.

Aged↗

Use of ethnoveterinary medicinal plants in cattle by Setswana-speaking people in the Madikwe area of the North West Province of South Africa.

Rapid Rural Appraisal (RRA) methods were employed to document the use of ethnoveterinary medicinal plants in cattle by Setswana-speaking people in the Madikwe area of the North West Province of South Africa. The study indicated that Setswana-speaking people in the North West Province have a rich heritage of ethnoveterinary knowledge, which includes all aspects of ethnoveterinary medicinal plant use. Information was gathered from informants through individual interviews, group interviews, guided field walks and observations. Ethnoveterinary uses in cattle of 45 plant species representing 24 families were recorded. Plants were used in 84% of the total number of recorded ethnoveterinary remedies. These plants were used alone (64%) or in mixtures (36%) for 29 indications. The most important indications were retained placenta, diarrhoea, gallsickness, fractures, eye inflammation, general ailments, fertility enhancement, general gastrointestinal problems, heartwater, internal parasites, coughing, redwater and reduction of tick burden. Plant materials were prepared in various ways including infusion, decoction, ground fresh material, sap expressed from fresh material, charred and dried. The most common dosage form was a liquid for oral dosing. Other dosage forms included drops, licks, ointments, lotions and powders. Liquid remedies for oral dosing were always administered using a bottle. Medicinal plant material was preferably stored in a dried form in a cool place out of direct sunlight and wind. Lack of transfer of ethnoveterinary knowledge to younger generations puts this knowledge at risk. RRA was found to be a successful method of investigation for the study of ethnoveterinary medicine.

Animals↗

Biobehavioral characteristics of nondemented older adults with subclinical brain atrophy.

OBJECTIVE: To characterize the risk factors and neuropsychological performance of two subgroups of community-dwelling, white elderly men free of severe cognitive impairment (n = 383; mean age, 72.9 +/- 3.0 years) who differ on volumetric measurements of total brain parenchyma and white matter hyperintensity (WMH) volumes. METHODS: Group comparisons were made of cerebrovascular disease risk factors measured at the time of imaging and at three prior examinations extending over 25 years of adult life. Measures of verbal memory and speed psychomotor processing at the time of imaging and 10 years before imaging were also available. RESULTS: Compared with those in the "nonatrophy" group, individuals in the subgroup with "atrophy" (defined by low total brain volume and high WMH volume) were older, reported a higher level of depressive symptomatology, experienced a steeper decline in diastolic blood pressure (DBP) and a steeper increase in pulse pressure, were less physically active, had smoked for more years, and had a higher prevalence of several cardiovascular disease indicators, including an ankle/arm systolic blood pressure ratio less than 0.9, and hypertension. After multivariate analysis, the 25-year decline in DBP, the number of years smoked, and an ankle/arm index of less than 0.9 remained significant discriminators of the two groups. Lower levels of speeded performance at the time of imaging and a steeper 10-year decline in cognitive performance on selected tests were also observed in the atrophic group. CONCLUSION: Community-dwelling older adults with volumetric brain measurements associated with accelerated aging are distinguishable on the basis of several health-related characteristics. These individuals also perform less well on certain tasks involving executive functioning.

Adult↗

Contribution of genetic and environmental influences to ankle-brachial blood pressure index in the NHLBI Twin Study. National Heart, Lung, and Blood Institute.

The ankle-brachial index (ABI) is widely used in the clinical diagnosis of peripheral arterial disease. The contributions of genetic and environmental influences to normal and abnormal ABI values are unknown. In this study, the authors used available data on 94 monozygotic pairs and 90 dizygotic pairs of elderly, White, male twins examined in 1995-1997 to investigate the contributions of genetic and environmental influences to normative ABI values. Within-twin-pair correlations for normative ABI values were statistically significant, and the correlation in monozygotic twin pairs was significantly greater than that in dizygotic pairs. Structural equation modeling of the variance-covariance matrices of monozygotic and dizygotic twins indicated that 48% of the observed variability in ABI values could be attributed to additive genetic effects. In contrast, concordance rates for low ABI values (ABI< or =0.9) for both monozygotic and dizygotic twins were significantly greater than would be expected by chance alone, but within-pair monozygotic similarity was not significantly greater than dizygotic similarity. A matched-cotwin analysis in 21 pairs that were discordant for low ABI values found that twins with low ABI values were physically less active and more likely to be persistent smokers than their normal-control brothers. These findings reinforce the role of individual health practices (e.g., physical activity, smoking) in the manifestation of peripheral arterial disease among subjects matched for age, genetics, and early shared environment.

Aged↗

Ten-year follow-up for male twins divided into high- or low-risk groups for ischemic heart disease based on risk factors measured 25 years previously.

PURPOSE: To undertake medical follow-up in white males in the National Heart, Lung, and Blood Institute (NHLBI) twin study, previously divided on the basis of cardiovascular disease risk factors. METHODS: Tree structured survival analysis (TSSA) used at a mean age of 63 years to classify twins into high and low risk subgroups for ischemic heart disease (IHD) found that subjects at a mean age of 48 years were at highest risk with high systolic blood pressures and low high density lipoprotein cholesterol levels. Low risk subjects had lower blood pressures, better pulmonary function tests, and a negative family history for IHD or low post load plasma glucose levels. Medical record review was performed ten years later at the 4th Examination of the NHLBI twin cohort conducted in 1995-1997. RESULTS: The percentage of men in the NHLBI twin study who died nearly tripled (from 9.3% to 25.8%) in the ten-year period between the ages of 63 and 73 years. Deaths have tended to remain higher in DZ than MZ twins (27.8% versus 23.7%). At Exam 4, the relative risk of IHD (fatal or non-fatal) was 5.24 times higher for those in the high risk group than those in the low risk class (95% confidence limit 2.72-10.07, p < 0.0001 and 5.86 for any cardiovascular disease (95% confidence limit 3.03-11.33). The proportion of deaths from IHD in subjects with a high risk profile at entry was 51.7%, and 70.0% had died from all cardiovascular related disease. CONCLUSION: The present results indicate TSSA remained effective in classifying subjects into subgroups with greater risk of morbidity and mortality related to cardiovascular disease after ten additional years.

Aged↗

Segregation analysis of drinking problem in elderly men and their first-degree relatives from the Western Collaborative Group Study.

PURPOSE: The purpose of this study is to determine the mode of inheritance of alcohol-related drinking problems. METHODS: Family history was collected by interview from 493 elderly male participants (probands) in a follow-up cardiovascular exam of healthy white men living in the San Francisco Bay Area and Los Angeles. Segregation analysis was used to test for the presence of a major gene effect underlying the liability to develop an alcohol-related drinking problem. RESULTS: The results showed that the liability to drinking problem is due, in part, to a single major gene with no residual effects from shared familial influences. CONCLUSIONS: These results suggest that at least one major gene is involved in the genetic predisposition to develop drinking problem in late adulthood.

Adult↗

Longitudinal changes in the contribution of genetic and environmental influences to symptoms of depression in older male twins.

Genetically informative longitudinal data on self-reported symptoms of depression allow for an investigation of the causes of stability and change in depression symptoms throughout adult life. In this report, the authors investigated the relative contribution of genetic and environmental influences to symptoms of depression in 83 monozygotic and 84 dizygotic male twin pairs from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study. Participants first completed the Center for Epidemiologic Studies-Depression (CES-D) scale in 1985-1986 and again during 1995-1997. Mean age of twins at baseline was 63 years, range 59 to 70. From cross-sectional genetic analyses we estimated the heritability of CES-D to be 25% (95% confidence interval [CI], 11%-39%) at baseline and 55% (95% CI, 40%-71%) at follow-up. Fitting longitudinal genetic models to the two-wave data, we found that stability of symptoms over the 10-year follow-up was due primarily to continuity of genetic influences.

Adult↗

Relationship of 30-year changes in obesity to sleep-disordered breathing in the Western Collaborative Group Study.

OBJECTIVE: Obesity is an important etiologic factor in sleep-disordered breathing (SDB), but the extent to which changes in obesity across adult life contribute independently to SDB in old age has not been studied. In this study, we examined the association between changes in obesity from midlife to late adulthood and overnight recording of respiration during sleep. RESEARCH METHODS AND PROCEDURES: Subjects in this study are from the Western Collaborative Group Study, a longitudinal cardiovascular epidemiological study that began in 1960 through 1961. Overnight sleep recordings were obtained from 281 male participants in the 1995 through 1996 follow-up of the Western Collaborative Group Study. Subjects were 75 to 91 years old when assessed for SDB as indexed by the respiratory disturbance index and an oxygen desaturation index (O2DI). Long-term changes in anthropometrics were evaluated and examined in relation to SDB severity. RESULTS: Over the 30 years of follow-up, body mass index and waist circumference increased significantly for this sample and were associated with SDB severity as indexed by respiratory disturbance index and O2DI. Waist circumference at baseline and gain in waist circumference over the 30 years of follow-up (both p = 0.01) were significantly and independently associated with SDB severity as assessed by O2DI. However, percentage of variance as accounted for by waist circumference was modest. DISCUSSION: This study supports the hypothesis that gain in waist circumference over adult life is significantly associated with SDB severity in older men.

Adipose Tissue↗

A genetic analysis of smoking behavior in family members of older adult males.

AIMS: To conduct a genetic study of smoking behavior in 493 three-generation families. DESIGN: Complex segregation analysis and maximum likelihood statistics were used to describe the familial clustering of ever-smoking under several transmission models. SETTING: The Western Collaborative Group Study, an ageing and health study currently in its 39th year of follow-up. PARTICIPANTS: Probands were male participants who were of mean age 71.6 years at the time of the family history interview in 1986-88. MEASUREMENTS: Data were collected via an interview that focused on the family smoking history of participants. Smoking histories of all first-degree relatives were obtained from probands. FINDINGS: Evidence for genetic transmission was indicated by rejection of both the environmental and sporadic models in favor of a Mendelian genetic model with residual familial effects from spouses and both parents. CONCLUSIONS: The best-fitting model was that of a dominant major gene with low estimated frequency and residual familial correlations. This is the first study to date to model the familial transmission of ever-smoking in three-generation families.

Aged↗

A high-performance liquid chromatographic method for the determination of monofluoroacetate.

A simple isocratic high-performance liquid chromatographic (HPLC) method for the quantitative analysis of monofluoroacetic acid (MFA), the toxic substance of Dichapetalum cymosum, in plant material, rumen contents (gastric contents), and liver samples is described. A suitable HPLC column that gives optimum sensitivity, accuracy, precision, and separation of MFA is identified. A C-610 organic acid analysis column at ambient temperature with 0.02M H3PO4 as an eluent and ultraviolet detection at 210 nm is utilized to quantitate MFA. Using this method, the average percentage recovery in plant material, bovine liver, and rumen samples is 94.8%, and a detection limit of 12 microg/L is achievable.

Animals↗