Search PubMed⌕ Search

Biomedical subjects

J T Powell

Publications and source records attributed to J T Powell.

At least 73 records · Page 4Linked to original sources
PubMed1996

Smoking impairs the activity of endothelial nitric oxide synthase in saphenous vein.

Smoking impairs the endothelium-dependent relaxation of arteries and veins, with the maximum relaxation in response to the calcium ionophore A23187 of saphenous vein rings being reduced from 53 +/- 4% in nonsmokers to 27 +/- 5% in smokers. We have investigated whether this endothelial dysfunction was attributable to altered activity or concentration of nitric oxide synthase (NOS). The concentration of NOS in saphenous vein endothelium, determined by Western blotting and immunohistochemistry, was not different in nonsmokers and smokers. Nitrite production from vein strips stimulated with A23187 was higher in nonsmokers (median 23.6 nmol.cm-2.h-1) than smokers (median 3.3 nmol.cm-2.h-1), P=.001, this difference being abolished when vein strips were preincubated in the presence of NG-monomethyl-L-arginine. Organ chamber studies to monitor the endothelium-dependent relaxation of vein rings in response to A23187 showed that preincubation of rings from smokers with either L-arginine (3mmol/L) or superoxide dismutase (250 U/mL) did not improve the maximum relaxation. In contrast, preincubation of vein rings from smokers with 20 micromol/L tetrahydrobiopterin increased the maximum relaxation from 27 +/- 5% to 51 +/- 6%, P=.01. Preincubation of vein from smokers with tetrahydrobiopterin also significantly increased nitrite and cGMP production in response to stimulation with A23187. The impaired endothelium-dependent relaxation of saphenous vein rings from smokers appears to be caused by a reduction in the activity of endothelial NOS that is attributable to an inadequate supply of the coenzyme tetrahydrobiopterin.

Adult↗
PubMed1995

The influence of fibrinogen concentration on the development of vein graft stenoses.

OBJECTIVE: The aim of this study was to identify factors associated with the development of graft stenoses in the first year after bypass. DESIGN AND SETTING: Between January 1992 and April 1993, 75 consecutive patients undergoing distal vein bypass surgery were entered into a graft surveillance programme at Charing Cross Hospital. The grafts (n = 79) were surveyed by colour flow Doppler ultrasonography at 7 days, 3, 6, 9 and 12 months and the site of stenoses (> 50%) recorded. Position of the distal anastomosis, graft type (in situ or reverse) and clinical history were recorded. At the 3-month surveillance a blood sample was taken for the estimation of smoking markers, lipids and fibrinogen. RESULTS: The site of the distal anastomosis was to the suprageniculate popliteal in nine, infrageniculate popliteal in 32 and tibio/peroneal vessels in 38 cases. In the first month following bypass there were six deaths, giving a 30 day mortality of 7.5%, three patients were lost to follow up, seven grafts occluded, three were replaced by PTFE, four patients underwent amputation and one patient had a redo vein graft. In the remaining grafts 20/63 (32%) developed stenoses within the first year after bypass. The development of a graft stenosis was not associated with sex, diabetic status, site of distal anastomosis, graft type or serum lipids. Multiple regression analysis identified only one factor associated significantly with the development of vein graft stenosis: fibrinogen concentration (p = 0.003). Life table analysis showed that after 1 year only 46% of grafts remained free of stenoses in patients with above median fibrinogen concentrations compared with 84% of grafts in patients with below median fibrinogen concentrations, p = 0.009. CONCLUSIONS: Increased plasma fibrinogen concentration is a potent risk factor for the development of vein graft stenosis. These results prompt consideration of the role of fibrinogen in stimulating smooth muscle cell proliferation in the stenotic lesion.

Aged↗
PubMed1995

Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm.

The risk of rupture of an abdominal aortic aneurysm increases with aortic diameter. To obtain insight into the pathological processes associated with the vascular remodeling that accompanies aortic dilatation, we compared the histological features and the activity of matrix metalloproteinases (MMPs) in biopsies from 21 small (4.0 to 5.5 cm in diameter) and 45 larger abdominal aortic aneurysms. The histological feature most clearly associated with enlarging aneurysm diameter was a higher density of inflammatory cells in the adventitia, P = .018. This inflammation was nonspecific, principally macrophages and B lymphocytes. Fibrosis of the adventitia provided compensatory thickening of the aortic wall as the aneurysm diameter increased. A combination of zymography and immunoblotting identified gelatinase A (MMP-2) as the principal metallogelatinase in small aneurysms, whereas zymography indicated an increasing activity of gelatinase B (MMP-9) in large aneurysms. Homogenates prepared from both small and large aneurysms had similar total activity against gelatin or type IV collagen. However, the concentration of gelatinase A, determined by immunoassay, was highest for small aneurysms: median concentrations, 385, 244, and 166 ng/mg protein for small aneurysms, large aneurysms, and atherosclerotic aorta, respectively. Immunolocalization studies indicated that gelatinase A was concentrated along fibrous tissue of both the acellular media and the atherosclerotic plaque. The recruitment of inflammatory cells into the adventitia, with subsequent elaboration of metalloproteinases, including gelatinase B, may contribute to the rapid growth and rupture of larger aneurysms.

Amino Acid Sequence↗
PubMed1995

[Mode of genetic inheritance of abdominal aortic aneurysm: still no clear answers].

Clear evidence has not yet come concerning the genetics of abdominal aortic aneurysms (AAA). There are circumstantial proof for a hereditary predisposition. In a retrospective study of sixty patients consecutively underwent a surgical repair for AAA, showed that one third of them knew a first-degree relative with the same disease. Environmental factors, such as smoking, ageing or hypertension, must be taken into account. A multifactorial mode of inheritance is under discussion due to both multiple genes with different expressivity and diverse environmental factors. Linkage-analysis or DNA sequencing of the different gene loci in population studies or sibbling-analysis are the tools in search for candidate genes for inheritance of AAA. Mutations in those genes encoding structural components of the aortic wall, such as collagen-type-III, fibrillin or elastin, are not taken to be the underligned genetic cause. Mutations in genes encoding enzymes for the turnover of the aortic wall components, such as alpha-1-antitrypsin or matrix-metalloproteinase-2, may play an important role.

Aortic Aneurysm, Abdominal↗
PubMed1994

Smoking and growth rate of small abdominal aortic aneurysms.

Smoking is an important risk factor for abdominal aortic aneurysm. Limiting the growth rate of small aneurysms has the potential to prevent them reaching a size at which surgical repair is considered. In 43 patients, with small aneurysms, growth rates were studied by serial ultrasound over 3 years. The median expansion rate of these small aneurysms was 0.13 cm per year. Growth rates were higher in those who continued to smoke (0.16 vs 0.09 cm per year in those who no longer smoked, p = 0.038). Higher growth rates were significantly correlated with the concentration of serum cotinine. Stopping smoking could reduce the growth rate of small abdominal aortic aneurysms.

Aged↗
PubMed1994

Pathogenesis of abdominal aortic aneurysm.

The pathogenesis of abdominal aortic aneurysm involves many factors acting over time. However, destruction of elastin in the aortic wall is a key event that shifts the load produced by blood pressure on to collagen. This is exacerbated in the presence of hypertension. Smoking and age are further important factors, as is the site; elastic lamellae are relatively less common in the abdominal aorta. Once the shielding effect of elastin is lost, further dilatation and rupture of the aorta depend on the physical properties of the collagen present.

Age Factors↗
PubMed1994

The use of duplex scanning to diagnose perioperative carotid occlusions.

Perioperative stroke following carotid endarterectomy is reported to occur in 3-20% of patients and may be associated with spontaneous development of thrombus at the operation site or technical imperfections. In 118 consecutive patients, duplex scanning performed immediately before anaesthesia was used to confirm that all high grade carotid stenoses had not progressed to occlusion since the arteriogram. A new technique at completion, using subcuticular prolene sutures for the skin and a plastic dressing for the wound, permitted immediate postoperative assessment by duplex scanning if necessary. Of the 118 patients, symptoms of neurological instability developed in 4 (3.4%) in the first 6 hours after surgery. At duplex scanning, developing thrombus was demonstrated in three of these patients. Arterial thrombus was removed at reoperation and all three patients recovered with no neurological deficit. The fourth patient had occluded the contralateral carotid artery, developed a major stroke and was not considered for re-exploration. Duplex scanning provides accurate diagnostic information in selecting patients for urgent re-exploration, reducing the 24 h stroke rate to 0.8% in this series.

Aged↗
PubMed1994

Is thickening of the basal lamina in the saphenous vein a hallmark of smoking?

OBJECTIVE: To investigate whether smoking causes ultrastructural changes in the intima of the proximal saphenous vein. DESIGN: Proximal saphenous veins from heavy smokers and non-smokers were examined with scanning and transmission electron microscopy to determine changes in surface ultrastructure, in the intercellular junction, and in the thickness of the basal lamina. Immunogold labelling was used to identify specific components of the endothelial basal lamina. MATERIAL: Vein specimens were obtained from patients undergoing varicose vein surgery (12 patients) or distal bypass surgery (eight patients). MAIN RESULTS: The only ultrastructural change that discriminated between specimens was thickening of the endothelial basal lamina. All specimens with a thickened basal lamina were from heavy smokers. Immunogold labelling studies showed that the thickened basal lamina contained specific accumulations of fibronectin but not heparan sulphate proteoglycans, type IV collagen, or laminin. CONCLUSIONS: Two ultrastructural characteristics are associated with smoking: thickening of the endothelial basal lamina and a specific accumulation of fibronectin in the thickened basal lamina. Such abnormalities in the saphenous veins from smokers may contribute to the poorer performance of these veins as bypass conduits.

Adult↗
PubMed1994

Are cerebral aneurysms atherosclerotic?

BACKGROUND AND PURPOSE: The aim of our study was to investigate plasma and genetic risk factors for rupture of cerebral aneurysms. METHODS: In London, a case-control study was made of 56 consecutive patients admitted to a regional neurosurgical service for treatment of ruptured cerebral aneurysm and of 93 control subjects. A further 40 consecutive patients admitted in Arhus with ruptured cerebral aneurysm also were studied. RESULTS: The British case-control study showed that smoking was associated with an increased risk of ruptured cerebral aneurysm (odds ratio, 9.1; 95% confidence interval [CI], 3.4 to 23.8; P < .001 for a history of > 10 pack years). After age and sex adjustment, factors associated with ruptured cerebral aneurysm included a cholesterol concentration in the highest tertile (> or = 6.3 mmol/L; odds ratio, 10.2; 95% CI, 3.9 to 26.7; P < .001), an apolipoprotein B concentration in the highest tertile (> or = 0.84 g/L; odds ratio, 6.4; 95% CI, 2.5 to 16.3; P < .001), and concentrations of HDL cholesterol in the lowest tertile (< 1.1 mmol/L; odds ratio, 3.6; 95% CI, 1.4 to 8.2; P < .01). History of hypertension was of less importance (odds ratio, 4.0; 95% CI, 1.41 to 11.7; P < .01). Smoking history (P < .001) and increased concentrations of cholesterol (P < .0001) were the most important independent risk factors associated with ruptured cerebral aneurysm on multivariate analysis. The histories of hypertension and smoking, together with apolipoprotein B levels, in the Danish patients were similar to those in the British patients. In the entire patient group, the frequencies of two polymorphic variations in the type III collagen gene and polymorphisms at the apolipoprotein B, apolipoprotein C-III, and haptoglobin gene loci were not different from control subjects or the normal population; allele frequencies in British and Danish patients were similar. CONCLUSIONS: An atherosclerotic profile including increased total cholesterol concentration and a long smoking history may contribute to the rupture of cerebral aneurysms. This study provides no support for the hypothesis that inherited abnormalities of type III collagen are a common cause of cerebral aneurysms.

Adult↗
PubMed1993

High prevalence of unsuspected abdominal aortic aneurysm in patients with confirmed symptomatic peripheral or cerebral arterial disease.

A group of 561 consecutive patients with proven symptomatic peripheral or cerebral arterial disease attending a vascular clinic was screened for abdominal aortic aneurysm (AAA) using B-mode ultrasonography. An aneurysm was present in 40 of 358 men (11.2 per cent) and 13 of 203 women (6.4 per cent), a total prevalence of 9.4 per cent. Thirty-three aneurysms were 3-4 cm in diameter. The prevalence of AAA was similar in patients referred with lower-limb and with cerebral ischaemia. Physical examination for AAA was performed in 200 patients before ultrasonography. The sensitivity of physical examination in the detection of aneurysm was 43 per cent (57 per cent for AAA > or = 4 cm in diameter, 29 per cent for AAA < 4 cm in diameter). Physical examination was an inadequate method of screening. Initial follow-up showed a mean aneurysm expansion rate of 0.20 cm/year. Patients with arterial disease have a high risk of AAA; routine ultrasonographic screening should be considered.

Aortic Aneurysm, Abdominal↗
PubMed1993

Smoking impairs endothelium-dependent relaxation of saphenous vein.

Samples of proximal saphenous vein were obtained from heavy smokers and non-smokers: 28 were obtained at varicose vein surgery and eight at infrainguinal bypass surgery. The veins were prepared for histological examination and for mounting in an organ bath to measure changes in isometric tension. Vein rings from both smokers and non-smokers responded equally to sodium nitroprusside, a reagent that acts directly on smooth muscle cells, undergoing 90-100 per cent relaxation. The mean(s.e.m.) maximum relaxation in response to bradykinin of rings obtained at varicose vein surgery was 50.0(5.3) per cent in non-smokers compared with only 31.6(2.2) per cent in smokers (P = 0.03). Similarly, in specimens obtained at bypass surgery the mean(s.e.m.) maximum relaxation in smokers was only 25.1(6.3) per cent compared with 48.4(4.1) per cent in smokers (P = 0.04). Relaxation in response to the bradykinin stimulus was abolished in the presence of L-nitroarginine methyl ester, a specific inhibitor of the synthesis of endothelium-derived relaxing factor (EDRF). Preincubation of the vein rings with L-arginine, the precursor of EDRF, did not increase the vasorelaxation in smokers. The mean(s.e.m.) maximum relaxation in response to the calcium ionophore A23187 was 53.5(3.8) per cent in non-smokers compared with only 27.0(4.9) per cent in smokers (P = 0.01). The results indicate that heavy smokers have impaired release of EDRF in response to both bradykinin and calcium ionophore. This impairment may increase vasomotor tone, platelet aggregation and smooth muscle proliferation, thereby resulting in an increased risk of graft occlusion.

Adult↗
PubMed1993

Influence of type III collagen genotype on aortic diameter and disease.

Type III collagen contributes to the tensile strength of the aortic wall, and mutations in the type III collagen gene have been suggested as the basis for the familial tendency to abdominal aortic aneurysm (AAA). Variation in this gene was investigated in 153 patients with AAA, 87 with aortoiliac stenosis and 98 age-matched controls. The rare mutation at amino acid 619 of Gly-->Arg, previously associated with AAA in a single family, was not found in any of the patients with aneurysm. For the Ala-->Thr variation at amino acid 531, the frequency of the threonine allele was 0.25 in patients with AAA and stenosis, compared with 0.35 in controls. The frequency of the rare allele in the region 3' to the gene demonstrated by Ava II digestion (0.27 in the general population) was found to be 0.29 in the AAA group and 0.19 in the stenosis group (P = 0.023). In the AAA group the presence of the Ava II rare allele was associated with a significant increase in aneurysm diameter (P = 0.044). Non-invasive assessment of aortic distensibility was available in 25 patients: those carrying the Ava II rare allele had less distensible aortas than those not carrying this allele (median pressure-strain elastic modulus 42.0 and 23.9 N/cm2 respectively, P = 0.008). Variation in the type III collagen gene may influence the mechanical properties of the ageing aorta and hence its susceptibility to disease and dilatation. In contrast, there is no evidence for a single common founder mutation in type III collagen predisposing to AAA.

Aged↗