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Biomedical subjects

R M Greenhalgh

Publications and source records attributed to R M Greenhalgh.

At least 55 records · Page 3Linked to original sources

Dilatation of saphenous vein grafts by nitric oxide.

OBJECTIVES: To investigate firstly whether flow-dependent vasodilation is maintained in vein grafts, and secondly whether nitric oxide donors dilate vein grafts to improve the flow through graft stenoses. DESIGN, MATERIALS AND METHODS: The vasodilatation of mature patent vein grafts, in response to reactive hyperaemia and glyceryl trinitrate (GTN), was assessed by the change in external diameter using duplex ultrasonography. The severity (ratio of proximal systolic velocity, V1, to peak systolic velocity at the stenosis, V2, of vein graft stenoses was determined by duplex ultrasonography before and after 24 h of local application of GTN patches. RESULTS: In post-occlusion hyperaemia the diameter of patent distal vein grafts (n = 7) increased to a maximum of 112 +/- 1.9% of resting diameter after 2 min, p = 0.026. The diameter increased further to 117 +/- 2.5% of the resting value 5 min after oral GTN (n = 5), p = 0.007. The velocity ratio, V2/V1, through graft stenoses (n = 6) decreased by 20 +/- 5% after application of GTN patches, principally as a result of reduction in V2, mean difference 0.8, p = 0.15. The changes in response to GTN were more evident for proximal than distal vein graft stenoses. CONCLUSION: Flow-induced vasodilatation responses, which have been attributed to the endothelial release of nitric oxide, are maintained in patent vein grafts: the grafts dilate even further in response to GTN. The application of GTN patches close to a vein graft stenoses appears to reduce the velocity ratio through vein graft stenoses. GTN patches might be used to reduce the risk of graft occlusion when there is a delay between the detection and the treatment of haemodynamically significant graft stenoses.

Administration, Cutaneous↗

The influence of diabetes on the vasomotor responses of saphenous vein and the development of infra-inguinal vein graft stenosis.

There has been a prejudice that diabetes modulates the function of saphenous vein in a manner that predisposes to bypass graft failure, although most of the evidence accrues from animal studies. We have investigated the effect of diabetes on the vasodilator responses and ultrastructure of saphenous vein harvested from patients undergoing infrainguinal bypass surgery for limb salvage and the development of stenoses within the vein grafts. Of 55 consecutive patients undergoing vein bypass surgery for critical ischemia, 16 (29%) were diabetic: diabetes was not a risk factor for graft stenosis, which occurred in 17 of 56 (30%) grafts. Endothelium-dependent relaxation by nitric oxide pathways stimulated after receptor activation (bradykinin and thrombin) was not different in vein rings from diabetic (n = 12) and nondiabetic patients (n = 12). Prostarioid-mediated vasorelaxation was absent in vein rings from diabetic patients, and the production of 6-keto prostaglandin F(1alpha) (PGF(1alpha)) from diabetic vein was only 66 +/- 27 pg x cm-2 x min-1 compared with 112 +/- 20 pg x cm-2 x min-1 from control vein (P = 0.011). Fibrinogen-mediated vasorelaxation, normally inhibited by K+ channel blockers, was negligible in vein from diabetic patients. No ultrastructural differences were observed between the endothelium of saphenous vein harvested from diabetic and nondiabetic patients. However, diabetes was associated significantly with the presence of spiraled collagen in media. The maintenance of receptor-activated stimulation of nitric oxide pathways and the damping of the response to fibrinogen in saphenous vein endothelium may provide, in part, for the good prognosis of vein graft surgery in diabetic patients: diabetes is not a risk factor for early (12 months) infrainguinal vein graft stenosis.

Aged↗

Carotid plaque characteristics and presenting symptom.

BACKGROUND: The importance of identifying features of carotid artery disease, in addition to degree of stenosis, which predict subsequent stroke is becoming increasingly clear. This study assessed the relationship between carotid plaque characteristics and presenting symptoms. METHODS: Some 285 symptomatic (transient ischaemic attack (TIA) 127, amaurosis fugax 58, transient stroke 15, established stroke 55, progressive stroke 11, crescendo TIA 19) and 65 asymptomatic patients were studied with colour-flow duplex imaging. All patients had 60-99 per cent internal carotid stenosis. Carotid plaque morphology (classified according to Gray-Weale) and plaque surface features were assessed. RESULTS: Plaque types I and II were more common in symptomatic patients (83 per cent versus 44 per cent; P < 0.0001). Plaque surface was classified as smooth (34 per cent), irregular (44 per cent) or ulcerated (22 per cent). Ulceration was also more common in symptomatic patients (23 versus 14 per cent; P = 0.04). In symptomatic patients there was no association between presenting symptom and plaque morphology or surface features (P = 0.9 and P = 0.8 respectively). On multiple regression analysis plaque morphology did not distinguish between patients who presents with stroke without warning and other symptomatic patients (who had TIA, amaurosis fugax, crescendo TIA or stroke with warning). CONCLUSION: There was an association between echolucent type I and II carotid plaques and the presence of symptoms but not their type. Plaque morphology was not characteristic in a subgroup of patients who had stroke without warning. Further prospective study of plaque morphology in asymptomatic patients might help identify high-risk groups.

Adult↗

Interaction between fibrillin genotype and blood pressure and the development of aneurysmal disease.

Debate as to whether abdominal aortic aneurysms (AAA) are caused by atherosclerosis or whether they have a strong genetic etiology continues. We have investigated the hypothesis that risk factors are likely to be strongest in patients with generalized aneurysmal disease. We screened 232 consecutive AAA patients for popliteal aneurysm and investigated cardiovascular and genetic risk factors in these patients. Ultrasonography demonstrated the presence of a popliteal aneurysm in 24 of 232 (10%) patients. Multivariate analysis identified four independent factors associated with popliteal aneurysm: age (p = 0.013), height (p = 0.017), triglyceride concentration (p = 0.009), and systolic blood pressure (p = 0.037). In the AAA patients a significant association of fibrillin-1 genotype was present, determined by a tandem repeat polymorphism, with both systolic and pulse pressure. The genotypes associated with the highest pressures were significantly more common among the patients with popliteal aneurysm, p = 0.03. Following these findings we investigated whether there was an association between fibrillin-1 genotype and blood pressure in a healthy population, 245 men aged 50-61 years. Again we found a significant association between fibrillin genotype and pulse pressure, p = 0.003. We suggest that a strong interaction occurs between fibrillin genotype and blood pressure which contributes to the development of aneurysmal disease.

Aging↗

Influence of patient-related variables on the outcome of carotid endarterectomy.

PURPOSE: Variability in outcome after carotid endarterectomy is well recognized. This study examines the importance of patient-related factors in determining outcome. METHODS: Four hundred and sixty consecutive patients undergoing carotid endarterectomy for symptomatic severe (60% to 99%) internal carotid stenosis performed by one vascular surgeon have been studied prospectively. Patients were followed-up at 3, 6, 9, and 12 months and then yearly. Pre-, intra-, and perioperative details and follow-up information were entered on a database. RESULTS: Multiple logistic regression identified a number of factors significantly associated with death and stroke. A history of crescendo transient ischemic attacks (TIAs) (p = 0.003, p = 0.0002) and being female (p = 0.03, p = 0.0001) were associated with both perioperative death and stroke within 30 days of operation, respectively. Deaths between 1 and 36 months were associated with ischemic heart disease (p = 0.03) and diabetes (p = 0.04), whereas stroke was associated with small internal carotid diameter (p = 0.02). The importance of symptoms at presentation on outcome was further emphasized by life-table analysis. In 98% of patients with amaurosis fugax, only 67% of those with crescendo TIAs were alive at 18 months (p < 0.01). The survival of patients with amaurosis was significantly better than those with TIAs (p < 0.01), transient stroke (p < 0.01), and progressive, stroke (p < 0.05). Similarly, postoperative stroke was significantly more common for patients with crescendo TIAs than those with amaurosis (p < 0.01), established stroke (p < 0.05), and TIA (p < 0.05). Transient stroke was associated with a poor outcome, with only 66% of patients being alive in 36 months and 14% having suffered a stroke (p < 0.05 compared with established stroke). CONCLUSION: Presenting symptoms significantly predict outcome after carotid endarterectomy. This should be considered both in patient selection and comparison of patient series.

Carotid Artery, Internal↗

Unravelling the familial tendency to aneurysmal disease: popliteal aneurysm, hypertension and fibrillin genotype.

PURPOSE: To screen patients with abdominal aortic aneurysm for popliteal aneurysm and investigate cardiovascular and genetic risk factors associated with aneurysmal disease at more than one site (generalised aneurysmal disease). SUBJECTS, DESIGN AND SETTING: All patients referred to the Regional Vascular Surgical Service at Charing Cross Hospital with unruptured abdominal aortic aneurysm between 1989 and 1993 were screened for popliteal aneurysms, using ultrasonography. MAIN OUTCOME MEASURES: Palpation of a popliteal aneurysm or ultrasonographic detection of popliteal dilatation, where the ratio maximum popliteal fossa diameter/suprageniculate popliteal diameter was > or = 1.5, in relation to cardiovascular and genetic risk factors. RESULTS: Clinical examination detected popliteal aneurysms in only 11/232 patients (5%), but ultrasonography demonstrated the presence of popliteal aneurysm in a further 13 patients, 24/232 in total (10%). Multivariate regression identified four independent factors associated with popliteal dilatation disease: age (p = 0.046), height (p = 0.006), systolic hypertension (p = 0.037) and triglyceride concentration (p = 0.009). Generalised aneurysmal disease and systolic blood pressure were associated with polymorphic variation in the fibrillin-1 gene, but not with variations in the apolipoprotein B and type III collagen genes. CONCLUSIONS: Few patients with abdominal aortic aneurysm (10%) also have popliteal aneurysms: the risk of popliteal dilatation increases with age, height, systolic blood pressure, triglyceride concentration and fibrillin genotype. The strong interaction between fibrillin genotype and blood pressure may contribute to the familial tendency to aortic aneurysm.

Age Factors↗

Have the results of infrainguinal bypass improved with the widespread utilisation of postoperative surveillance?

OBJECTIVES: The objectives of this study were to assess the impact of Duplex surveillance on the results of infrainguinal vein grafts. A review has been performed comparing the outcome of vein grafts undergoing Duplex surveillance plus prophylactic treatment of stenoses to that of vein grafts followed clinically. DESIGN, PATIENTS, AND METHODS: Only studies providing information on occlusion rates were included. Mortality and limb salvage rates were also analysed but were not available from all studies. RESULTS: 2680 surveillance and 3969 non-surveillance vein grafts were analysed. There was no significant difference between the two groups with respect to presence of critical ischaemia (p=0.3) and level of distal anastomosis (p>0.5). Surveillance identified 493 stenoses in 469 (19%) grafts, 397 (16%) grafts were treated by surgery (248; 62%) and angioplasty (149; 38%). Ninety-eight (26%) grafts developed recurrent stenoses. Total number of deaths, total number of occluded grafts and number of occlusions after 30 days were significantly greater for the non-surveillance group (p<0.001; p<0.001; p<0.01). Perioperative occlusion rates were not significantly different (p=0.1). Few surveillance studies reported limb salvage rates (6 of 17). The numbers of amputations were not significantly different between the two groups (p>0.5). CONCLUSIONS: The patency of infrainguinal vein grafts would appear to be improved as a result of surveillance. However, no improvement in limb salvage has been demonstrated.

Arteriovenous Shunt, Surgical↗

The influence of smoking cessation and hypertriglyceridaemia on the progression of peripheral arterial disease and the onset of critical ischaemia.

OBJECTIVE: To investigate whether smoking and other cardiovascular risk factors were associated with deterioration of ankle/brachial pressure index or onset of critical ischaemia in patients with mild to moderate intermittent claudication. DESIGN AND SETTING: Longitudinal study in a London teaching hospital. SUBJECTS: 415 consecutive smokers, with symptoms of intermittent claudication and an ankle/brachial pressure index of <0.9, referred for a surgical opinion between April 1985 and December 1990, who were not considered for an immediate surgical procedure. MAIN OUTCOME RESULTS: Reduction in ankle/brachial pressure index of >0.14, onset of critical limb ischaemia. RESULTS: After one year of follow up 183 patients (44%) had stopped smoking (as evaluated by biochemical markers). With longer follow up only 110 patients (27%) had maintained smoking cessation. There were no differences in age, sex, and previous tobacco exposure between stoppers and smokers, but the proportion of diabetics among stoppers (20%) was greater than among those who continued smoking (10%) [p=0.01]. The annual rate of deterioration of ABPI was 21, 16 and 17% respectively in the first, second and third year of follow-up and the onset of critical ischaemia was observed in 52 patients (12.5%) during the period of follow-up. In univariate analyses, continued smoking, diabetes and presence of ischaemic heart disease were not associated with an increased risk of deterioration of ABPI, but hypertriglyceridaemia (> or = 2.2 mmol/l) was, [relative risk 1.7(95% CI 1.21-2.37), p=0.003], and patients having systolic blood pressure in the middle tertile (153-170 mmHg had a reduced risk of deterioration of ABPI, p=0.026. Hypertriglyceridaemia (> or = 2.2mmol/l) was the only independent factor associated with deterioration of ABPI in multivariate analysis [relative risk 1.8(95% CI:1.23-2.59), p=0.003] and also was associated with a relative risk of onset of critical ischaemia of 1.9 [(95% CI: 1.08-2.87), p=0.035], compared with triglyceride levels of <2.2mmol/l. CONCLUSION: For those with mild to moderate claudication, the lack of immediate benefit from cessation of smoking appears to be associated with a gradual return to smoking. Hypertriglyceridaemia was identified as the most important independent factor associated with the progression of peripheral arterial disease and onset of critical ischaemia.

Aged↗

Outcome of selective patching following carotid endarterectomy.

OBJECTIVES: Routine patch angioplasty has been advocated following carotid endarterectomy but patching can be associated with complications. This study assesses the effect of a selective patching policy based on distal internal carotid diameter on the rate of restenosis and outcome following carotid endarterectomy. DESIGN, MATERIAL AND METHODS: A consecutive series of 213 patients underwent carotid endarterectomy performed by one surgeon. Preoperative carotid dimensions were measured intraoperatively using calipers. Following endarterectomy a 5mm Dacron patch was selectively employed if the distal internal carotid was 5mm or less (group 1, 95 patients) or 6mm or less (group 2, 118 patients). Patients underwent colour-coded Duplex scanning at 24 h, 1 week, 3, 6, 9, and 12 months, and yearly following this. RESULTS: Overall 27 restenoses (5 residual) of 50% or greater and two occlusions developed. Patching was performed in 47% of group 1 and 61% of group 2 arteries. In group 1 14% of patched compared with 24% of non-patched arteries developed restenosis at 24 months (p=0.4). In group 2 13% of patched compared to 11% of non-patched arteries developed restenosis at 12 months (p>0.5). Stroke rate at 24 months were similar for patched and non-patched patients in groups 1 (p>0.5) and 2 (p=0.4). CONCLUSIONS: This study suggests that patch angioplasty of larger carotid arteries may be unnecessary. Randomisation of larger arteries between patch and primary closure would be required to confirm this.

Aged↗

Risk factors for abdominal aortic aneurysms in smokers.

OBJECTIVE: To investigate features of the smoking habit and other cardiovascular risk factors associated with the development of abdominal aortic aneurysm in smokers. DESIGN AND SETTING: Case control study of smokers recruited, between 1989 and 1992, in a London teaching hospital. SUBJECTS: Consecutive smokers referred with abdominal aortic aneurysm (cases n=44) and 244 age and sex-matched smokers attending Dermatology, Orthopaedic and Urology clinics (controls). MAIN RESULTS: Hypertension was more common amongst the patients with aneurysm (30%) than the controls (19%). Measured systolic and diastolic blood pressures were significantly higher in the aneurysm patients. The relative risk of having an abdominal aortic aneurysm increased 3.4-fold (95% CI 1.06-10.89) for those with a diastolic blood pressure of >90mmHg, p=0.035 and 4.1-fold (95% CI 1.27-13.16) for those with a mean arterial pressure > or = 100mmHg, p=0.009. Plasma lipids, fibrinogen and cotinine were similar amongst patients with aneurysm and controls. The cumulative smoking exposure was similar in the patients with aneurysm and controls, median 49 and 44 pack-years respectively. The relative risk of developing an aneurysm increased with the number of cigarettes currently smoked, p=0.008, and with increasing depth of inhalation, p=0.025, but was not associated with the tar or nicotine yield of current cigarettes. CONCLUSIONS: In smokers, the risk of developing an abdominal aortic aneurysm increases with increasing mean arterial and diastolic blood pressure and two aspects of current smoking habit: the number of cigarettes currently smoked and the depth of inhalation.

Aged↗

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↗

Assessment of feasibility for endovascular prosthetic tube correction of aortic aneurysm.

Abdominal aortic aneurysm (AAA) can now be corrected by perfemoral introduction of a prosthetic tube graft with fixation using expandable metal stents. This technique requires a satisfactory iliac system, through which the graft can reach its destination, and suitable lengths of non-aneurysmal aorta below the renal arteries and above the aortic bifurcation for stent attachment. The feasibility for placement of endovascular grafts was assessed in 44 consecutive patients admitted for transabdominal AAA repair. The proximal and distal aneurysmal necks and the iliac arteries were assessed before operation by colour flow Doppler ultrasonography (duplex scanning), computed tomography and intravenous digital subtraction angiography, using intraoperative measurements as the 'gold standard'. At operation 32 of 44 patients had a suitable proximal neck and five of 44 a suitable distal neck for endovascular grafting. Duplex scanning was the most accurate modality for preoperative assessment of the aneurysm necks. According to this technique 32 of 44 patients had a satisfactory iliac system for introduction of an endovascular graft. Overall only four of 44 patients were considered suitable for endovascular correction of AAA using a tube graft-stent combination.

Aged↗

In vitro evaluation of endovascular stents to assess suitability for endovascular graft fixation.

OBJECTIVE: To compare and ascertain the suitability for endovascular aortic graft fixation of the Palmaz stent, the Strecker stent, the modified Gianturco-Z stent, the Wallstent and a new stent made of the shape memory alloy nitinol. DESIGN, SETTING AND MATERIALS: In vitro studies using a simple tensiometer to assess the forces required to distract each stent from porcine aorta; and using a high-pressure, pulsatile-flow pump to measure flow rates required to dislodge stents holding grafts within porcine aortas, with assessment using endovascular ultrasound. RESULTS: The Palmaz, the modified Gianturco-Z and the nitinol stents resisted significantly greater distraction forces than the Wallstent, but endovascular ultrasound examination revealed that the modified Gianturco-Z stent was seen to move away from the aortic wall at high flow rates precluding adequate fixation. The Strecker stent could not be assessed using these techniques. CONCLUSIONS: A nitinol stent may be suitable for aortic graft fixation, has characteristics similar to the Palmaz stent and has shape memory effect which may overcome the difficulties of introduction of wider diameter stents through narrow arteries.

Alloys↗