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Biomedical subjects

A Owen

Publications and source records attributed to A Owen.

At least 37 records · Page 2Linked to original sources

Clinical predictors of pulmonary hypertension in patients undergoing liver transplant evaluation.

Clinical prediction of portopulmonary hypertension (PPHTN) is critical in the preoperative evaluation of candidates for orthotopic liver transplantation (OLT) because of its association with significant morbidity and mortality. To determine the clinical, laboratory, and echocardiographic predictors of PPHTN, we retrospectively evaluated 55 candidates before OLT. From those, 8 candidates had pulmonary hypertension ([HTN] group A) and 47 candidates did not (group B). Pulmonary HTN was defined as a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater and either elevated pulmonary vascular resistance or normal pulmonary artery wedge pressure. The significant predictors of PPHTN were (1) systemic arterial HTN (63% in group A v 9% in group B; P <.001), (2) loud pulmonary component of the second heart sound (38% v 2%; P =. 001), (3) right ventricular (RV) heave (38% v 4%; P =.002), (4) RV dilatation by echocardiogram (63% v 0%; P <.001), (5) RV hypertrophy by echocardiogram (38% v 0%; P =.001), and (6) echocardiogram-estimated systolic PAP (SPAP) greater than 40 mm Hg (63% v 2%; P <.001). The sensitivity of these variables for the detection of pulmonary HTN ranges from 37% to 63%, and their specificity from 91% to 100%. We conclude that several clinical and echocardiographic features are significantly associated with pulmonary HTN in patients with cirrhosis. In particular, echocardiogram-estimated SPAP greater than 40 mm Hg is strongly associated with pulmonary HTN and is specific. These predictors, however, are not sensitive enough to identify all the patients with PPHTN. Therefore, the evaluation of a combination of these variables may be useful for the preoperative identification of pulmonary HTN in liver transplant candidates.

Case-Control Studies↗

Experience of commencing Carvedilol in elderly patients with heart failure in a routine outpatient clinic.

Carvedilol has been shown to be beneficial for patients with heart failure, but it is not clear how it should be initiated in routine clinical practice, particularly in the elderly. This study is a retrospective review of 19 patients of age 80+/-4 years with heart failure, who had Carvedilol treatment initiated in a routine outpatient clinic. No patient experienced a worsening of their heart failure or required admission to hospital. There was a mean reduction in heart rate of 11 beats/min. Carvedilol was tolerated by 68% of the patients. Thus, Carvedilol can be safely initiated in a routine outpatient clinic in appropriately selected elderly patients.

Administration, Oral↗

Effect of an exercise programme for elderly patients with heart failure.

AIMS: Benefit from exercise training programmes for patients with chronic heart failure has been demonstrated in relatively young (mean age 60 years) and predominantly male subjects. This study was undertaken to assess the effect of an exercise programme for older subjects more representative of the general heart failure population. METHODS AND RESULTS: Twenty-two patients with chronic heart failure of mean age 81+/-4 years were recruited into the study. Twenty-five percent were female and 31% were in chronic atrial fibrillation. A crossover study design was employed. The programme consisted of once weekly exercise sessions tailored to the abilities of elderly subjects and lasted for 12 weeks. Fifteen subjects completed the exercise component and nine the control component. The programme resulted in a 20% relative increase in 6-min walk test distance (ANCOVA: P<0.012). There was no improvement in quality of life as measured by the Living With Heart Failure Questionnaire, but the majority of subjects reported subjective improvement in wellbeing. CONCLUSION: Elderly patients with chronic heart failure can benefit from an appropriately designed exercise programme and should not be excluded from future large scale trials.

Aged↗

The effect of calcium ionophore A23187 on neurites from embryonic mouse spinal cord explants in culture.

The calcium channel ionophore A23187 has been shown to cause a striking reduction in both the rate of neurite outgrowth and in growth cone motility; it has also been shown that these changes may be reversed when the ionophore is removed from the culture medium. The evidence supports the view that a specific concentration range of calcium is essential for outgrowth and motility and that calcium influences neuronal growth by an effect on actin structures within the growth cone. Using time-lapse video microscopy techniques, the effects of calcium ionophore A23187 on the rate of neurite outgrowth and growth cone motility in cultured embryonic mouse spinal cord neurons were examined. Concentrations in the range of 1-100 microM resulted in an inhibition of neuronal outgrowth, a loss of filopodia and a significant reduction in survival after seven hours. The results show that although the treatment with A23187 inhibited growth at all concentrations used, motility was inhibited only at the highest concentration indicating that the optimum calcium concentration for motility is higher than that for growth and that calcium mediates its effects on growth and motility at a very local level.

Animals↗

Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity.

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00 +/- 0.15, 5.36 +/- 0.17 (P < 0.01), 5.63 +/- 0.13 (P < 0.05) mmol/l, respectively for total cholesterol; 4.13 +/- 0.15, 3.64 +/- 0.15 (P < 0.05), 3.82 +/- 0.12 (P < 0.05) mmol/l, respectively for LDL-cholesterol; 48.19 +/- 9.90, 26.59 +/- 5.53 (P < 0.03), 25.12 +/- 4.62 (P < 0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r = -0.27, P < 0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16 +/- 0.07 mmol/l) than in the premenopausal group (0.96 +/- 0.07) or postmenopausal group not using HRT (0.87 +/- 0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.

Analysis of Variance↗

Chronic L-DOPA treatment increases striatal cannabinoid CB1 receptor mRNA expression in 6-hydroxydopamine-lesioned rats.

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the left medial forebrain bundle and 3 weeks treatment with L-DOPA of normal and 6-OHDA lesioned rats on CB1r mRNA expression was investigated by in situ hybridization. A 6-OHDA lesion of nigrostriatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA, did not alter CB1r mRNA levels in the dopamine depleted striatum. Similarly, chronic L-DOPA treatment of normal rats had no effect on striatal CB1r mRNA expression. In contrast, chronic L-DOPA treatment of 6-OHDA-lesioned rats significantly increased CB1r mRNA expression in the denervated striatum. These results suggest that the CB1r activity may be altered by L-DOPA's action and this may be related to the treatment of Parkinson's disease.

Adrenergic Agents↗

Effect of increasing age on diastolic motion of the left ventricular atrioventricular plane in normal subjects.

AIMS: To determine the effect of ageing on diastolic motion of the atrioventricular plane in normal subjects. METHODS AND RESULTS: One hundred normal subjects (age range 43 to 78 years) underwent an echocardiographic examination and determination of diastolic motion of the atrioventricular plane. The total displacement declined with increasing age at the septum (p<0.01) but not at other sites. The rate of change of early displacement declined with increasing age at all sites (p<0.001). The displacement due to atrial systole increased with increasing age (p<0.05). CONCLUSION: Important changes in diastolic function in normal subjects occur in the fifth and sixth decades. This may relate to the change in calcium metabolism within the myocardium seen with increasing age. It is not possible to determine from the study whether these changes are due to ageing per se or to environmental factors associated with ageing.

Adult↗

The use of Doppler and atrioventricular plane motion echocardiography for the detection of changes in left ventricular function after training.

In this study we compared the efficacy of Doppler and atrioventricular plane motion echocardiography in detecting the changes in left ventricular function caused by moderate-intensity training. Fifty-nine healthy men and women (aged 40-68 years) were divided into either a group of walkers (n = 32) or controls (n = 27). Pre-intervention, there were no significant differences between the groups for gender, age, height, mass or predicted maximal oxygen consumption. The walkers completed a progressive 18-week walking programme that resulted in an estimated mean gross energy expenditure whilst walking of 4.0 (1.3) MJ x week(-1) for the duration of the study, and 5.9 (1.7) MJ x week(-1) during the final 6 weeks. After the 18-week programme there were no significant changes in Doppler measures of early or late filling velocities. However, the walkers showed an increase in the velocity of relaxation (1.2 cm x s(-1)) (P < 0.02) of the left free wall, as measured using atrioventricular plane motion echocardiography, while the controls showed no significant changes. The findings suggest that atrioventricular plane motion echocardiography is more sensitive than Doppler echocardiography in detecting the left ventricular changes caused by exercise intervention.

Adult↗

The efficacy of accumulated short bouts versus single daily bouts of brisk walking in improving aerobic fitness and blood lipid profiles.

Fifty-six subjects (19 men and 37 woman) aged between 40 and 66 completed the study. They were allocated into three walking groups and a control group (C). The three walking groups performed the same total amount of walking for 18 weeks, but completed it in bouts of differing durations and frequencies. These were Long Walkers (LW; 20-40 min/bout), Intermediate Walkers (IW; 10-15 min/bout) and Short Walkers (SW; 5-10 min/bout); with the IW and SW performing more than one bout of walking a day. Following the 18 week walking programme, compared to the C group all walking groups showed similar improvements in fitness as determined by a reduction in blood lactate during a graded treadmill walking test (LW 1.0 mmol/l; IW 0. 8 mmol/l; SW 1.2 mmol/l; C 0.2 mmol/l; P = 0.003) and reduction in final heart rate (LW 8 beats/min; IW 6 beats/min; SW 10 beats/min; C 0 beats/min; P = 0.056). Also compared to the C group, the LW and IW groups recorded statistically significant decreases in low-density lipoprotein cholesterol (LW 0.29 mmol/l; IW 0.41 mmol/l; P = 0.024), whereas the control group showed a mean increase of 0.22 mmol/l. The LW and IW groups also showed significant reductions in apolipoprotein (apo) A-II (LW 0.05 g/l; IW 0.02 g/l; SW 0.01 g/l; C 0.00 g/l; P = 0.012) with the LW recording a statistically significant increase in the ratio of apo A-I/A-II (LW, 0.19, P = 0. 044). In conclusion, some health benefits were achieved from all walking programmes. However, whilst the changes in aerobic fitness were similar, the effects upon blood lipid profiles were not. The findings from this study suggest that the LW regimen was most effective in benefiting blood lipid profile, followed by the IW regimen, with the SW being least potent. Nevertheless, for the sedentary/low-active members of society, any improvement in health may be considered as important. Therefore accumulated bouts of moderate intensity exercise, which according to theories of exercise behaviour may be more easily incorporated into an individual's lifestyle than single prolonged bouts, may be advocated for health promotion but may not be as effective as the traditionally prescribed 20-40 min bouts.

Adult↗

Neurite outgrowth-regulating properties of GABA and the effect of serum on mouse spinal cord neurons in culture.

Time-lapse photography was used to examine the effects of gamma-aminobutyric acid (GABA) on the outgrowth and motility of neurites in cultures from mouse spinal cord. GABA at concentrations of 100, 10 and 1 microM caused significant inhibition of neurite outgrowth and the motility of growth cones was significantly reduced by treatment with 100 and 10 microM GABA. This effect was mimicked by the GABA(B) receptor agonist baclofen, whereas the GABA(A) receptor agonist muscimol had no effect. The effect of GABA on outgrowth and motility seems to be dependent on the type of serum employed. The results reported here were obtained only when heat-inactivated serum was used and not when non heat-inactivated serum was added to the culture medium. They suggest that GABA has a role in the regulation of process outgrowth within the embryonic mouse spinal cord.

Animals↗

Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease.

Depletion of reduced glutathione occurs in the substantia nigra in Parkinson's disease and in incidental Lewy body disease (presymptomatic Parkinson's disease) which may implicate oxidative stress in the neurodegenerative process. In this study mercury orange fluorescent staining and immunostaining with an antibody to reduced glutathione have been used to determine the distribution of reduced glutathione in the substantia nigra in Parkinson's disease compared with normal individuals. Mercury orange staining showed moderate background levels of fluorescence in the neuropil in both control and Parkinson's disease substantia nigra and localised reduced glutathione to the somata of melanized nigral neurons and glial elements of the neuropil. Neuronal nuclei revealed a relative lack of fluorescence after mercury orange staining. There was a significant depletion of reduced glutathione in surviving neurons in Parkinson's disease compared to nerve cell populations in control tissue. Mercury orange fluorescence indicated a high concentration of reduced glutathione in a subpopulation of non-neuronal cells, most likely astrocytes or microglia. Immunohistochemical examination of nigral tissue from the same Parkinson's disease and control patients with an antibody to glutathione showed staining in neuronal perikarya and axonodendritic processes of melanized nigral neurons which was generally most intense in control neurons. Moderately intense staining of the background neuropil, most prominent in control nigras, and staining of capillary walls was also detected. Intense staining was seen in cells with the morphological features of glial cells in both control and PD nigra. These data show a significant presence of reduced glutathione in the cell bodies and axons of nigral neurons. They are in agreement with biochemical studies showing depletion of reduced glutathione in substantia nigra in Parkinson's disease, and indicate a significant loss of neuronal reduced glutathione in surviving nigral neurons in Parkinson's disease.

Aged↗

Uterus-like mass arising in the broad ligament: a metaplasia or mullerian duct anomaly?

A 46-year-old woman presented with a large abdominopelvic mass. Exploration revealed a large cystic mass that arose from the posterior leaf of the right broad ligament. The mass was lined by endometrial-like tissue and had an outer layer of smooth muscle that resembled myometrium. The inner wall was focally composed of a thick layer of intermixed smooth muscle and endometrial glands comparable to adenomyosis. This is the fourth reported case of "a uterus-like mass" and the first that is clearly extraneous to the ovary. We hypothesize that these masses may arise from subperitoneal mesenchymal cells that retain the ability to duplicate mullerian duct structures; other cases may represent mullerian duct fusion defects.

Broad Ligament↗

Effects of an 18 week walking programme on cardiac function in previously sedentary or relatively inactive adults.

OBJECTIVE: To investigate the effects of an 18 week walking programme upon cardiac function. METHODS: 29 sedentary or relatively inactive but otherwise healthy subjects (15 walkers and 14 controls, aged 40-68 years) completed the study. The walkers completed a progressive 18 week walking programme which required an estimated average energy expenditure of 900 kcal week-1 for the total duration of the study and 1161 kcal week-1 during the final six weeks. Walking was carried out at an intensity of 67.8 (SD 4.99)% of maximum oxygen consumption and 73.8(6.99%) of maximum heart rate. Before and after the intervention all subjects underwent an M mode echocardiogram, graded treadmill walking test, and step test for the assessment of aerobic fitness. RESULTS: After 18 weeks the results of the control group showed no change in any of the variables measured while the walkers showed a statistically significant increase in the velocity of relaxation of the longitudinal myocardial fibres of the left ventricle and a decrease in heart rate measured during the step tests, indicating an improvement in aerobic capacity. CONCLUSIONS: Walking promotes improvements in cardiovascular fitness. Moderate forms of exercise may improve cardiac function.

Adult↗

Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women.

The possibility that the heightened cardiovascular risk associated with the menopause, which is said to be ameliorated by soybeans, can be reduced with soy isoflavones was tested in 21 women. Although several were perimenopausal, all have been included. A placebo-controlled crossover trial tested the effects of 80-mg daily isoflavones (45 mg genistein) over 5- to 10-week periods. Systemic arterial compliance (arterial elasticity), which declined with age in this group, improved 26% (P < .001) compared with placebo. Arterial pressure and plasma lipids were unaffected. The vasodilatory capacity of the microcirculation was measured in nine women; high acetylcholine-mediated dilation in the forearm vasculature was similar with active and placebo treatments. LDL oxidizability measured in vitro was unchanged. Thus, one important measure of arterial health, systemic arterial compliance, was significantly improved in perimenopausal and menopausal women taking soy isoflavones to about the same extent as is achieved with conventional hormone replacement therapy.

Adult↗