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Biomedical subjects

L Swan

Publications and source records attributed to L Swan.

At least 19 recordsLinked to original sources
PubMed2006

Transcatheter device closure of atrial septal defects in the elderly: technical considerations and short-term outcomes.

BACKGROUND: Device closure of an atrial septal defect (ASD) results in symptom-reduction, right heart remodelling and lower pulmonary artery pressures. However it is unclear if there is a chronological limit to these benefits and whether device closure is safe in elderly subjects. The aim of this study was, therefore, to assess the safety and efficacy of device closure in patients >60 years. METHODS: Retrospective study of Amplatzer Septal Occluder device closures from a single institution (May 1999-August 2002). RESULTS: Fifty subjects aged >60 years (range 60-85 years) had ASD device closure (27% of the total cohort). Defect size and shunt size were similar for both younger and older groups (2.2:1 in both groups, p=0.9) as were procedural duration, fluoroscopy time and device size deployed. Baseline right ventricular (RV) systolic pressure ((younger vs. older) 39 vs. 49 mmHg, p<0.001) and right ventricular size (45 vs. 51 mm, p<0.001) were greater in the older group. Following closure RV systolic pressure (49 vs. 45 mmHg, p<0.01) and RV size (51 vs. 44 mm, p=0.01) decreased in the older group. CONCLUSION: Device closure of an ASD can be performed safely in older patients. The right heart shows signs of remodelling even in elderly subjects.

Aged↗
PubMed2004

Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins.

OBJECTIVE: The precise interactions between glucocorticoids and leptin are complex and poorly understood. The aim of the study was to investigate whether the glucocorticoid/leptin interaction is influenced by shared environmental or genetic factors. DESIGN: We investigated the heritability of body mass index (BMI), circulating leptin and urinary glucocorticoid metabolites [tetrahydrocortisol (THF), alloTHF and tetrahydrocortisone (THE)] in 54 monozygotic (MZ) and 39 dizygotic (DZ) female twins. Analysis was performed using a structural equation modelling package Mx, developed by Neale. RESULTS: Leptin and BMI showed substantial heritability (68.3% and 71.3%, respectively). Bivariate analysis indicated that the genetic determinants of BMI and leptin are partly shared. Total cortisol metabolites (THF + alloTHF + THE), the (THE + alloTHF)/THE ratio [a marker of 11beta-hydroxysteroid dehydrogenase (11HSD) activity] and the alloTHF/THF ratio (marker for 5alpha-reductase activity) followed an environmental pattern. The heritability of leptin was significantly lowered to 63.8% (P = 0.012) when values were corrected for the influence of total cortisol metabolites but unaffected by markers of 11HSD and 5alpha-reductase activity. CONCLUSIONS: We confirm that the genetic influence on both BMI and the circulating leptin concentration is substantial and show that these genetic determinants are highly correlated. These genetic factors, which are more likely to be dominant than additive, can be modestly but significantly modified by urinary total cortisol metabolites implying an adrenal influence.

Adult↗
PubMed2003

The determination of carotid intima medial thickness in adults--a population-based twin study.

INTRODUCTION: Although cardiovascular events are known to cluster in families it is unclear the extent to which atherosclerosis per se is genetically determined. The aim of this study was to assess the heritability of carotid intima media thickness (IMT) measurements, a surrogate marker of early atherosclerosis, using a population-based twin study methodology. METHODS: B-mode carotid artery ultrasound images were acquired on 264 twin subjects (142 monozygotic (MZ); mean age 54.3 years and 122 dizygotic (DZ); mean age 51.7 years). An estimate of genetic determination, heritability, was calculated for the IMT parameters before and after correction for confounding variables. RESULTS: An increased carotid IMT was associated with known cardiovascular risk factors (total cholesterol r=0.24, P<0.001 and systolic blood pressure r=0.42, P<0.001) and with a history of coronary events (0.79+/-0.12 vs. 0.72+/-0.14, P=0.01). Carotid IMT measurements demonstrated a familial influence (intra-class correlation of 0.54 for MZ vs. 0.39 for DZ) but no specific genetic determination (heritability estimate 0.31, P=0.15). CONCLUSION: Within a normal population carotid IMT is under a familial, but not genetic influence. The mechanism of genetic control over cardiovascular events may not be mediated through atherosclerotic load as measured by IMT.

Adult↗
PubMed2003

The genetic determination of left ventricular mass in healthy adults.

AIMS: The extent to which left ventricular (LV) mass, an independent cardiovascular risk factor, is determined by genetic factors is unclear. The aim of this study was to assess the heritability of LV mass and its association with three potential candidate genes. METHODS: A population-based adult twin study model was utilized. Echocardiographic assessment of LV mass was performed in 110 twin pairs (mean age 55.9+/-10.9 years). An estimate of genetic determination, heritability, was calculated for the main echocardiographic parameters. The cohort were genotyped for the G-protein beta-3, aldosterone synthase, and beta-1 adrenoceptor genes. RESULTS: The intra-class correlation coefficients for LV mass were 0.69 for monozygotic (r-MZ) twins and 0.32 for dizygotic (r-DZ) twins, P=0.008 (heritability estimate of 0.69). This pattern persisted following correction for known confounding factors. Within-pair differences in the monozygotic, discordant and concordant dizygotic twins showed no differences for the three genes with respect to left ventricular wall thickness or mass. There was a non-significant trend towards a relationship between LV mass and the beta-1 adrenoceptor genotype. CONCLUSION: Within a normal population left ventricular mass has a significant genetic determination. Further investigation of potential candidate genes is required.

Cohort Studies↗
PubMed2003

Exercise systolic blood pressures are of questionable value in the assessment of the adult with a previous coarctation repair.

BACKGROUND: The role of exercise testing in the follow up of adults with a coarctation repair is unclear. Exercise induced systolic hypertension has been advocated as an indication for further investigation; however, the value of exercise testing in this role has been questioned, especially in paediatric populations. OBJECTIVE: To assess the value of resting and exercise blood pressure measurements in a cohort of adults with repaired coarctation. SETTING: Tertiary referral centre for adult congenital cardiac disease. PATIENTS: 56 patients (33 male, 23 female) with a previous coarctation repair, and 33 age matched controls. MAIN OUTCOME MEASURES: Resting and exercise blood pressures, including arm-leg systolic blood pressure gradients; standard echocardiographic measurements of left ventricular mass, aortic root diameter, and repair site gradient. RESULTS: The coarctation cohort had higher resting upper limb blood pressures than the controls (systolic: 129.7 v 120.7 mm Hg, p = 0.014; diastolic: 76.8 v 72.2 mm Hg, p = 0.02). Mean resting arm-leg systolic blood pressure gradient was also higher, at 3.6 v -2.2 mm Hg, p = 0.027. However, there were no differences between the peak exercise systolic blood pressures of the two groups. Peak exercise systolic blood pressure did not correlate with resting arm-leg blood pressure gradient (r = 0.24, p = 0.13) or with repair site gradient (r = 0.14, p = 0.39). Resting upper limb systolic blood pressure and resting arm-leg systolic blood pressure gradient were related to repair site gradient (r = 0.33, p = 0.03, and r = 0.47, p = 0.002). CONCLUSIONS: Measurements of upper limb blood pressure during exercise are of limited value in the assessment of the post-repair coarctation patient. If routine exercise testing is to be advocated in this population it must be for another indication.

Adult↗
PubMed2001

An influence of variation in the aldosterone synthase gene (CYP11B2) on corticosteroid responses to ACTH in normal human subjects.

OBJECTIVE: Previous evidence suggests that the efficiency of 11beta-hydroxylase is at least partly heritable and also that it may be mildly impaired in essential hypertension. In both cases, assessment of activity was based on the response of 11-deoxycorticosterone (DOC) and 11-deoxycortisol to ACTH. The gene (CYP11B1) coding for this enzyme is highly homologous with and lies a relatively short distance downstream from the gene coding for aldosterone synthase (CYP11B2) on chromosome 8. Two polymorphisms of CYP11B2 have been described. The first involves a change of -344C to T in a putative steroidogenic factor-1 (SF-1) binding site and the other, the intron conversion, an exchange of intron 2 for that of CYP11B1. These polymorphisms are in linkage dysequilibrium. Their effects on 11beta-hydroxylation were studied. METHODS AND RESULTS: Normal subjects (n = 135) were genotyped and those homozygous for either or both the polymorphisms were given ACTH (250 microg, i.v.). Plasma was sampled before and 30 minutes after administration. Basal concentrations of DOC, corticosterone, 11-deoxycortisol and cortisol and responses of corticosterone and cortisol to ACTH were not affected by genotype. However, the responses of DOC (P = 0.002 and P = 0.001, respectively) and 11-deoxycortisol (P = 0.025 and P = 0.002, respectively) were significantly greater in subjects homozygous for SF-1 T and/or intron conversion than in those homozygous for SF-1 C and/or normal intron. CONCLUSIONS: These results indicate different 11beta-hydroxylase efficiencies. Thus, variation in CYP11B2 appears to affect the product of CYP11B1. The mechanism is unclear. The close proximity of the two genes may lead to competition for transcription factors or specific differences in intron 2 may affect transcription. Alternatively, the polymorphisms may be acting as markers for adjacent functional genetic variations.

Adrenocorticotropic Hormone↗
PubMed2001

Unilateral spatial neglect.

Unilateral spatial neglect is a complex, but fascinating, deficit in attention that may occur following stroke. The phrase "unilateral spatial neglect" belies the complex mixture of disorders in representational memory, hypokinesia in the opposite hemispace, and inattention to sensory stimuli in the opposite hemispace. Unilateral spatial neglect occurs as a result of damage to the posterior parietal cortex, frontal lobe, cingulate gyrus, striatum, thalamus, or specific brain-stem nuclei. This neural network for attention is an excellent example of how different anatomic areas work together to produce a specific behavior. Traditional treatment strategies for USN have focused on training attention in the left hemispace using a variety of techniques, including sensory awareness, visual scanning, and spatial organization. Recently, additional treatment strategies have emerged that focus on representational aspects of brain functioning. These strategies have included visual and movement imagery,30 manipulation of sensory input that conveys perception of the head in space, and manipulation of visual input using prisms and eye patches. The complex nature of USN provides numerous directions for future research. Continued research will play a pivotal role in devising effective treatment strategies for patients with USN.

Attention↗
PubMed2000

Exercise prescription in adults with congenital heart disease: a long way to go.

OBJECTIVE: To determine if appropriate advice had been given to adults with congenital heart disease regarding safe and effective exercise, and to assess pre-existing misconceptions of the potential benefits and dangers of exercise. DESIGN: An anonymous self assessment questionnaire. SETTING: A tertiary referral clinic. PATIENTS: 99 adults (57 men, 42 women) with congenital heart disease, mean age 25.6 years. MAIN OUTCOME MEASURES: The extent and nature of exercise advice given over previous years; a measure of current activity level compared with the American Heart Association recommendations; and an assessment of exercise limiting symptoms and a description of barriers to further exercise. RESULTS: 44% of the cohort assumed all exercise was safe despite their cardiac disease. A health care professional had only raised the issue of specific exercise advice in 28 cases. Of those given instruction it was more common to receive prohibitive advice (30%) than to be encouraged to take more exercise (19%). Despite this 61% were involved in some form of at least light exercise. The most prevalent barriers to exercise were current symptoms (32.3%), lack of interest in exercise (24.2%), and health fears (16.1%). CONCLUSIONS: The education of adults with congenital heart disease regarding exercise and its potential benefits and limitations is suboptimal even in a specialist clinic.

Adolescent↗
PubMed1999

Hemodynamic and coronary effects of intravenous eletriptan, a 5HT1B/1D-receptor agonist.

OBJECTIVE: To investigate the systemic, pulmonary, and coronary artery effects of eletriptan, a new 5HT1B/1D-agonist in patients undergoing cardiac catheterization. METHODS: Ten patients (two men and eight women) without significant obstructive coronary artery disease were administered 3.33 microg/kg/min intravenous eletriptan after they were given a placebo infusion of 0.9% saline solution. Serial measurements of right heart and systemic pressures were taken at 5-minute intervals during placebo infusion, eletriptan infusion, and a 30-minute postinfusion period. Cardiac output by the thermodilution technique and coronary angiography were performed every 15 minutes. Quantitative coronary angiography was carried out to measure coronary artery dimensions. RESULTS: A small but statistically significant increase in occluded wedge pressure (7.4 versus 8.8 mm Hg; 95% confidence interval [CI], 0.74, 2.51; P < .01), right atrial pressure (5.3 versus 6.1 mm Hg; 95% CI, 0.0, 1.4; P < .05), and mean pulmonary artery pressure (13.2 versus 14.6 mm Hg; 95% CI, 0.0, 2.7; P = .05) was observed during the eletriptan infusion compared with placebo. A statistically significant increase in systemic vascular resistance (1256 versus 1519 dyne/sec/cm(-5); 95% CI, 126, 398; P < .01) and pulmonary vascular resistance (76.4 versus 100.8 dyne/sec/cm(-5); 95% CI, 1.9, 46.9; P < .05) was observed in the period after drug infusion. No overall effect was observed on the coronary arteries, although a segmental right coronary artery constriction developed in one patient, possibly as a result of catheter-induced spasm. CONCLUSIONS: Eletriptan, a 5HT1B/1D-agonist effective in migraine, causes no significant coronary artery constriction in patients without significant obstructive coronary artery disease. This finding may reflect a relative selectivity for the 5HT1D-receptor subtype.

Adult↗
PubMed1999

The haemodynamic effect of the 5HT1 agonist BMS-180048: a class effect of triptans?

AIMS: To investigate the effects of an intravenous infusion of BMS-180048, a novel 5HT1-like agonist, on the systemic, pulmonary and coronary circulations in patients undergoing diagnostic cardiac catheterisation. METHODS: Ten patients (mean age 55 years (range 41-65)) were studied during diagnostic cardiac catheterisation. The haemodynamic response to an intravenous (i.v.) infusion for 30 min of BMS-180048 (0.56 mg kg(-1) h(-1) for 10 min and 0.39 mg kg(-1) h(-1) for 20 min) was assessed via a 7F Swan Ganz catheter and thermodilution cardiac output system. Quantitative coronary angiography was performed at 10 min intervals. RESULTS: BMS-180048 caused a significant increase in systemic arterial systolic blood pressure (rise of 32.5 mmHg, 95% CI 24,44.5) P=0.009), pulmonary artery systolic (12.2 mmHg, 95% CI 6.8,18.5; P=0.009) and diastolic pressures (8.5 mmHg, 95% CI 5.0,13.8; P=0.009), right atrial pressure (4 mmHg, 95% CI 1.5,5.2; P=0.013) and pulmonary capillary wedge pressure (9.5 mmHg 95% CI 5.2,14.0; P=0.09). There was no significant change in cardiac output (0.1 l min(-1), 95% CI -0.17,0.57, P>0.05). Mean coronary artery diameter in the proximal coronary segments decreased by 0.73 mm (95% CI -1.22,-0.15; P=0.03) at 35 min. The corresponding reduction in middle segments was 0.26 mm (95% CI -0.395,-0.08; P=0.02). There was a non-significant trend to constriction in the most distal segments of 0.28 mm (95% CI -0.68,0.015); P=0.06). One patient experienced chest pain with ECG changes suggestive of ischaemia. CONCLUSIONS: BMS-180048 displayed a cardiovascular profile similar to that previously reported for sumatriptan. These changes appear to reflect a class effect of these agents.

Adult↗
PubMed1999

Effects of subcutaneous naratriptan on systemic and pulmonary haemodynamics and coronary artery diameter in humans.

Naratriptan, an effective antimigraine agent, is a selective 5-hydroxytryptamine (5-HT1 )-receptor agonist with a pharmacologic profile similar to that of sumatriptan. The object of this study was to assess the haemodynamic effects of naratriptan in a clinical model previously applied to sumatriptan. Cardiac haemodynamics and coronary artery diameter were measured at baseline and after subcutaneous injections of placebo and naratriptan (1.5 mg, s.c.) in 10 patients undergoing diagnostic cardiac catheterisation. No statistically significant change in mean coronary artery diameter was observed after naratriptan [95% confidence interval (CI), -0.27-0.11 mm: p = 0.37]. Naratriptan injection was associated with statistically significant increases in systolic arterial pressure (95% CI, 7.6-22.0 mm Hg; p = 0.0015), total systemic vascular resistance (95% CI, 74-253 dyn/s/cc; p = 0.003), pulmonary artery systolic pressure (95% CI, 2.0-6.9 mm Hg; p = 0.003), pulmonary vascular resistance (95% CI, 3-34 dyn/s/cc; p = 0.025), and pulmonary artery wedge pressure (95% CI, 1.9-2.4 mm Hg; p = 0.009). Naratriptan, a selective 5-HT1-receptor agonist, caused a vasopressor response in the systemic and pulmonary arterial circulations but was not associated with coronary artery vasoconstriction.

Adult↗
PubMed1999

Familial pattern of corticosteroids and their metabolism in adult human subjects--the Scottish Adult Twin Study.

Corticosteroids are important in the regulation of normal physiology and are key factors in regulating cardiovascular physiology and disease, the development of which is known to have a genetic component. However, there is little information on the extent to which plasma and urine steroid levels are determined by familial and genetic factors. We have examined basal and ACTH-stimulated plasma steroid levels and 24-h corticosteroid metabolite excretion rates in 146 pairs of adult twins [75 monozygotic (MZ); 71 dizygotic (DZ)]. Intraclass correlation coefficients were measured for all variables; several plasma steroid measurements were strongly related in both (MZ) and (DZ) twins, consistent with a familial pattern. These included basal levels of 11-deoxycortisol and aldosterone. ACTH-stimulated plasma aldosterone levels were also significantly correlated, to a significant degree, in both MZ and DZ twins. The index of 11beta-hydroxysteroid dehydrogenase activity (tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone) and of the more specific index of activity of the type 2 isoform of this enzyme (urine free cortisol/cortisone) also correlated, to a similar degree, in DZ and MZ twins. In contrast, for the basal and ACTH-stimulated plasma concentrations and 24-h urine excretion rates of several corticosteroids, there was evidence of significant heritability (H2), in that correlation in MZ twins was greater than in DZ. For example, basal plasma corticosterone concentrations (B) (H2 = 0.44), basal and stimulated 11-deoxycorticosterone concentrations (DOC) (H2 = 0.44 and 0.41, respectively), stimulated 11-deoxycortisol concentrations (H2 = 0.53), and the index of 11beta-hydroxylase activity DOC/B (H2 = 0.49) were all significantly heritable. For the urinary variables, 24-h tetrahydrodeoxycortisol (H2 = 0.59) and free aldosterone (H2 = 0.56) were significantly heritable. Our data provide the first evidence that plasma and urine levels of important glucocorticoids and mineralocorticoids show a strong familial pattern, and in some instances, there is evidence of a genetic component to this. This suggests that corticosteroids have a plausible role in essential hypertension that has a similar heritable component.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Multiple system atrophy.

Multiple system atrophy is a neurological disorder that has gone unrecognized for too long due to its involvement across multiple regions of the central nervous system. This disorder is finally being unveiled through increased reporting in the scientific literature. Further research will enhance our understanding of this disease and lead to more effective treatment regimens as well as an improved quality of life for patients with MSA.

Algorithms↗