P.R.F. Bell

University of Leicester, Leiscester, England, United Kingdom

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Publications (455)2467.13 Total impact

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    ABSTRACT: The objective of this review was to identify causes of stroke/death after carotid endarterectomy (CEA) and to develop transferable strategies for preventing stroke/death after CEA, via an overview of a 21-year series of themed research and audit projects. Three preventive strategies were identified: (i) intra-operative transcranial Doppler (TCD) ultrasound and completion angioscopy which virtually abolished intra-operative stroke, primarily through the removal of residual luminal thrombus prior to restoration of flow; (ii) dual antiplatelet therapy with a single 75-mg dose of clopidogrel the night before surgery in addition to regular 75 mg aspirin which virtually abolished post-operative thromboembolic stroke and may also have contributed towards a decline in stroke/death following major cardiac events; and (iii) the provision of written guidance for managing post-CEA hypertension which was associated with virtual abolition of intracranial haemorrhage and stroke as a result of hyperperfusion syndrome. The pathophysiology of peri-operative stroke is multifactorial and no single monitoring or therapeutic strategy will reduce its prevalence. Two of the preventive strategies developed during this 21-year project (peri-operative dual antiplatelet therapy, published guidance for managing post-CEA hypertension) are easily transferable to practices elsewhere.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 06/2013; 46(2). DOI:10.1016/j.ejvs.2013.05.005 · 2.49 Impact Factor
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    A.R. Naylor · Z Mehta · P M Rothwell · P R F Bell ·
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    ABSTRACT: To determine the role of carotid artery disease in the pathophysiology of stroke after coronary artery bypass (CABG). Systematic review of the literature. The risk of stroke after CABG was 2% and remained unchanged between 1970-2000. Two-thirds occurred after day 1 and 23% died. 91% of screened CABG patients had no significant carotid disease and had a <2% risk of peri-operative stroke. Stroke risk increased to 3% in predominantly asymptomatic patients with a unilateral 50-99% stenosis, 5% in those with bilateral 50-99% stenoses and 7-11% in patients with carotid occlusion. Significant predictive factors for post-CABG stroke included; (i) carotid bruit (OR 3.6, 95% CI 2.8-4.6), (ii) prior stroke/TIA (OR 3.6, 95% CI 2.7-4.9) and (iii) severe carotid stenosis/occlusion (OR 4.3, 95% CI 3.2-5.7). However, the systematic review indicated that 50% of stroke sufferers did not have significant carotid disease and 60% of territorial infarctions on CT scan/autopsy could not be attributed to carotid disease alone. Carotid disease is an important aetiological factor in the pathophysiology of post-CABG stroke. However, even assuming that prophylactic carotid endarterectomy carried no additional risk, it could only ever prevent about 40-50% of procedural strokes.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 09/2011; 42 Suppl 1:S73-83. DOI:10.1016/j.ejvs.2011.06.020 · 2.49 Impact Factor
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    ABSTRACT: The technique of subintimal angioplasty has been attempted on 200 consecutive femoropopliteal artery occlusions of median (range) length 11 (2-37) cm. The principle of the technique is to traverse the occlusion in the subintimal plane and recanalise by inflating the angioplasty balloon within the subintimal space. The technical success rate was 159/200 (80%) and was not significantly different for occlusions <10 cm (81%, n = 73), 11-20 cm (83%, n = 63) or >20 cm (68%, n = 23), p = 0.20. There were no deaths nor limb loss resulting from the procedure. The median (range) ankle-brachial pressure index increased from 0.61 (0.21-1.0) preangioplasty to 0.90 (0.26-1.50) postangioplasty. The actuarial haemodynamic patencies of technically successful procedures at 12 and 36 months were 71% and 58% respectively, the symptomatic patencies were 73% and 61%. A multiple regression analysis showed that smoking multiplied the risk of reocclusion by 2.70 (p < 0.001), each additional run-off vessel reduced the risk by 0.54 (p < 0.001) and the risk increased by 1.73 (p = 0.020) for every 10 cm of occlusion length. In conclusion, the technical success rate (80%) of subintimal angioplasty for femoropopliteal occlusions is unrelated to occlusion length and for all procedures, including technical failures, cumulative symptomatic and haemodynamic patencies of 46 and 48% can be achieved at 3 years. The factors influencing long-term patency were smoking, the number of calf run-off vessels and occlusion length.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 09/2011; 42 Suppl 1:S9-15. DOI:10.1016/j.ejvs.2011.06.018 · 2.49 Impact Factor
  • Kosmas I Paraskevas · Dimitri P Mikhailidis · Peter R F Bell ·
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    ABSTRACT: The General Anesthesia vs. Local Anesthesia for Carotid Surgery (GALA) trial did not show a difference in 30-day postoperative stroke, myocardial infarction and death rates between patients undergoing carotid endarterectomy (CEA) under local vs. general anesthesia. The present article discusses some limitations of the GALA trial. Firstly, the expected stroke and death rates following CEA is so low, that it was unlikely that the GALA trial would show any significant difference between local and general anesthesia. Secondly, preoperative statin use was not recorded. Thirdly, intraoperative shunt usa ge rates (a possible parameter for the development of stroke) varied considerably between the 2 groups (43% vs. 14%, for general vs. local anesthesia, respectively; P < .0001), as well as between UK and non-UK surgeons who always (73.6% vs. 20.8%, respectively; P < .0001), never (4.2% vs. 26%, respectively; P < .0002), or selectively (22.2% vs. 53.2%, respectively; P < .0001) used a shunt. Furthermore, no information was provided regarding the type of shunts used; for example, atraumatic shunts may be associated with lower perioperative stroke rates. These limitations could influence the interpretation of the results of the GALA trial. Due to lack of differences between the 2 groups and the presence of the above limitations, it seems likely that this trial will have little effect on clinical practice.
    Vascular and Endovascular Surgery 08/2009; 43(5):429-32. DOI:10.1177/1538574409340589 · 0.66 Impact Factor
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    ABSTRACT: Platelet function exhibits circadian variation with highest levels of activity in the morning and plays a central role in arterial thrombotic events, including thrombotic stroke following carotid endarterectomy (CEA). Prior to the platelet-rich thrombus occluding the carotid artery, multiple embolic signals are detected in the middle cerebral artery using transcranial Doppler ultrasound. We hypothesized that patients undergoing CEA early in the day may be at an increased stroke risk and this would manifest as an increased postoperative embolic count. Data were collected prospectively on 235 patients undergoing primary CEA. Accurate start and finish times were recorded in addition to the number of postoperative emboli detected in the first three hours after CEA using transcranial Doppler (TCD) monitoring. For operations finishing before midday, there was a 3.6-fold increase in the number of emboli detected relative to afternoon finishes (53.2 vs 14.8, P = .002) with similar results for starts before 10:30 AM (48.1 vs 14.7, P =.002). There was also a significant correlation between start time and emboli count (P = .02). Of the 55 patients with no postoperative emboli, only 19 had a morning start (relative risk 0.63, P = .011). Patients were 6.9 times more likely to require treatment with Dextran-40 to prevent progression onto a thrombotic stroke if their CEA finished before midday (P = .008). There is a significantly increased rate of postoperative embolization for operations begun earlier in the day. Carotid endarterectomies performed in the afternoon may be at less risk of developing postoperative thrombotic stroke.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 03/2009; 50(1):48-53. DOI:10.1016/j.jvs.2009.01.011 · 3.02 Impact Factor
  • I.M. Loftus · K.J. Molloy · J. Evans · P.R.F. Bell · A.R. Naylor · M.M. Thompson ·
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    ABSTRACT: Background: Loss of interstitial collagen, especially type I collagen, renders atherosclerotic plaques prone to rupture. Subsequent thrombosis and embolism may cause stroke and myocardial infarction. Initiation of collagen breakdown requires interstitial collagenases, a matrix metalloproteinase (MMP) subfamily including MMP-8. The aim of this study was to quantify the level of MMP-8, the enzyme that preferentially degrades type I collagen, in carotid plaques, and to correlate this with features of plaque instability.Methods: Plaques were retrieved from 75 consecutive patients undergoing carotid endarterectomy. MMP-8 levels were quantified using ELISA. Histological plaque sections were assessed blindly for the presence of plaque rupture and immunostaining was performed for MMP-8. All patients underwent preoperative transcranial Doppler monitoring to detect spontaneous embolization. Results expressed as median MMP-8 concentration ng mL−1 (IQR).Results: The plaque level of MMP-8 was significantly higher in patients with recent symptoms (symptoms <4 weeks), histological plaque rupture and spontaneous embolization (see Table). There was a significant correlation between MMP-8 and MMP-9 levels, a gelatinase known to be associated with plaque instability. Immunohistochemistry revealed staining for MMP-8 in areas of intense inflammatory infiltration.Discussion: The MMP-8 level is significantly higher in unstable plaques based on symptoms, histology and spontaneous embolization. Together with MMP-9, these enzymes have the potential to degrade all components of the extracellular matrix upon which plaque integrity depends, and represent a target for pharmacotherapy to prevent stroke.
    British Journal of Surgery 01/2009; 89(S1):14 - 14. DOI:10.1046/j.1365-2168.89.s.1.23_3.x · 5.54 Impact Factor
  • Article: Moynihan 05
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    ABSTRACT: Aims: Postoperative thromboembolic stroke affects 2–3 per cent of patients undergoing carotid endarterectomy (CEA) and is preceded by 1–2 h of increasing embolization. The hypothesis underlying the current study was that preoperative administration of a platelet ADP antagonist (clopidogrel) would reduce embolization and was based on previous studies showing that the platelets of patients with the highest rates of postoperative embolization had increased platelet reactivity to ADP.Methods: Total 100 CEA patients on routine aspirin therapy (75 mg) with an accessible TCD window were randomized to 75 mg clopidogrel (n = 47) or placebo (n = 53) the night before surgery. Platelet function was assessed by flow cytometry. The number of emboli detected by transcranial Doppler within 3 h of CEA was independently quantified. Time taken from restoration of flow to skin closure was used as an indirect measure of the time to secure haemostasis.Results: Clopidogrel significantly reduced platelet activation in response to ADP (P < 0.05) whilst conferring a fourfold reduction in the number of patients with >10 emboli in the postoperative period (OR 4.4, 95 per cent CI: 1.4–14.4; P < 0.008). However, the time from flow restoration to skin closure was >40 min in 30 per cent of clopidogrel patients compared with 8 per cent of controls (P < 0.004).Conclusions: This is the first study to show that a CEA patient's postoperative thromboembolic potential can be significantly reduced by preoperative pharmacotherapy. It remains to be seen whether a lower dose of clopidogrel will confer a similar reduction in embolization whilst reducing the time to achieve haemostasis.
    British Journal of Surgery 01/2009; 89(S1):38 - 38. DOI:10.1046/j.1365-2168.89.s.1.15_5.x · 5.54 Impact Factor
  • Article: Vascular 10
    J. Evans · I.M. Loftus · P.R.F. Bell · J.T. Powell · M.M. Thompson ·
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    ABSTRACT: Aims: The loss of elastin and subsequent weakening of the aneurysmal aortic wall is mediated by high levels of matrix metalloproteases and inflammatory cytokines. HMG CoA reductase inhibitors (‘statins’) may offer a pharmacotherapeutic strategy to prevent aneurysm expansion due to inhibition of both MMP formation and cytokine secretion.Methods: Elastin degradation was examined in a porcine model of aneurysmal disease. Sections of 1 cm2 of healthy porcine aorta were treated with elastase for 24 h to initiate an inflammatory and proteolytic response. Following organ culture with incremental doses of simvastatin for 14 days, tissue was harvested for histological examination and MMP activity. The inflammatory response within aortic tissue was examined using full thickness human aneurysmal explants cultured in simvastatin for 48 h. Cytokine production was measured in the conditioned medium by ELISA, and MMP activity quantified by substrate gel zymography.Results: Addition of simvastatin to the culture medium resulted in preservation of elastin and reduction in the levels of MMPs and interleukin-6.Conclusions: Simvastatin has beneficial effects on the inflammatory and proteolytic processes within the aneurysmal aortic wall, and has the potential to retard aneurysm expansion in clinical trials.
    British Journal of Surgery 01/2009; 89(S1):22 - 22. DOI:10.1046/j.1365-2168.89.s.1.10_10.x · 5.54 Impact Factor

  • British Journal of Surgery 01/2009; 89:38-38. · 5.54 Impact Factor
  • M. J. Bown · T. Horsburgh · M. L. Nicholson · P. R. F. Bell · R. D. Sayers ·

    British Journal of Surgery 01/2009; 89:34-34. · 5.54 Impact Factor
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    ABSTRACT: Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man. Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry. Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls. These data are consistent with a rise in plasmin due to dextran blockade of tPA uptake in vivo, leading to enhanced fibrinolysis, cleavage of vWF and of the platelet protease-activated receptor-1 (PAR-1) thrombin receptor. This suggests that dextran exerts a combined therapeutic effect, enhancing endogenous fibrinolysis, whilst also reducing platelet adhesion to vWF and platelet activation by thrombin. The proven antithrombotic efficacy of low-dose dextran in carotid surgery may be applicable to wider therapeutic use.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 07/2008; 48(3):715-22. DOI:10.1016/j.jvs.2008.04.008 · 3.02 Impact Factor
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    A Ross Naylor · Peter R F Bell ·
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    ABSTRACT: The landmark trials of the 1980s established a powerful precedent for demanding that "evidence" rather than "intuitive reasoning" should determine practice regarding management of patients with carotid disease. Accordingly, for our opponents to succeed in this debate, they must first demonstrate that there is little remaining confusion regarding the optimal management of asymptomatic carotid disease and then provide compelling evidence that it is now reasonable to offer carotid angioplasty with stenting without the protection of randomized trials. It is our contention that neither can be demonstrated and that the motion cannot be sustained.
    Seminars in Vascular Surgery 07/2008; 21(2):100-7. DOI:10.1053/j.semvascsurg.2008.02.001 · 1.38 Impact Factor
  • Peter R F Bell ·
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    ABSTRACT: BACKGROUND The optimum treatment strategy for patients with severe asymptomatic carotid artery stenosis who require cardiac surgery has not been established. OBJECTIVES To assess the effectiveness and safety of prophylactic carotid angioplasty and stenting ( CAS) prior to cardiac surgery in patients with severe asymptomatic carotid stenosis. DESIGN This was a prospective, observational study of consecutive patients scheduled to undergo CAS and cardiac surgery between December 1997 and June 2005 at St Antonius Hospital, Nieuwegein, The Netherlands. All participants had an indication for cardiac surgery (i. e. coronary artery disease with myocardial ischemia, dissection or aneurysm of the ascending aorta or aortic arch, or symptomatic valve disease) and severe (> 80%) carotid stenosis, and none had experienced an ipsilateral cerebrovascular event in the 4 months preceding enrollment. Patients were excluded if they had severe diffuse atherosclerosis, peripheral vascular disease that prevented femoral catheterization, severe renal impairment ( serum creatinine >= 300 mu mol/l), or a major neurological deficiency. INTERVENTION All patients received clopidogrel ( loading dose 300 mg then 75 mg/day) and aspirin ( loading dose 300 mg then 100 mg/day) for 3 days before femoral access CAS. The procedure was deemed successful if stenting achieved residual stenosis of 30% or less. Cardiac surgery (CABG surgery, reconstruction of the ascending aorta, or valve surgery) was scheduled for 14 30 days after CAS. Antiplatelet medication was discontinued 5 days before surgery. OUTCOME MEASURES The primary outcome measure was combined incidence of death and stroke at 30 days after cardiac surgery. Secondary end points were myocardial infarction (MI) and the composite of MI, stroke, or death 30 days after surgery, and cumulative event rates at 5-years' follow-up. RESULTS A total of 356 patients ( mean age 72.9 years) underwent CAS followed by cardiac surgery. The success rate for CAS was 97.7%. The mean duration between CAS and cardiac surgery was 22 days ( range 1 day to 3 months). CABG surgery was performed in 319 patients (89.6%), of whom 23 underwent off-pump surgery. At 30 days after surgery, the combined stroke and death rate was 4.8% (n = 17) and the rate of MI, stroke, or death was 6.7% ( n = 24); 7 patients (2.0%) suffered a nonfatal MI. During the 30-day follow-up period there were 13 deaths (3.7%), of which eight had a cardiac cause, one had a neurological cause, and four were caused by septicemia or multiorgan failure. The 5-year survival rate was 75.5%. Although patients aged 80 years or over had a significantly higher neurological and cardiac death rate than younger patients at 30 days ( P = 0.03), the difference was not significant at 5 years. All cardiac and neurological deaths in the octo genarians occurred within 2 days of surgery. CONCLUSION In this cohort of patients, a strategy of CAS followed by cardiac surgery is associated with low short-term and long-term rates of stroke, MI, and death.
    Nature Clinical Practice Cardiovascular Medicine 06/2008; 5(5):246-7. DOI:10.1038/ncpcardio1162 · 7.04 Impact Factor
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    E G Shifrin · W S Moore · P R F Bell · R Kolvenbach · E I Daniline ·
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    ABSTRACT: The aim of this study was to assess the efficacy of a new stapling device using a pig model. Straight 12 mm Gore-Tex grafts were inserted end to end into the aorta of 12 pigs. One anastomosis was performed with the stapler and the other using 4/0 prolene sutures and 13 mm needles. The animals were sacrificed at one week, one and three months and all grafts underwent histological examination. Leakage from the anastomoses was assessed in a separate specially designed circulation model using saline as a perfusate. The stapled anastomoses took 1.0+/-0.25 minutes to complete while suturing took 8.5+/-1.5 minutes. There was no difference in the histology between the two types of anastomosis. The leak rate was six times greater at the sutured compared to the stapled anastomosis. The use of stapled anastomoses may allow a significant shortening of aortic cross clamping time, reduce anastomotic leakage and may be particularly useful in laparoscopic aortic repair. A randomised trial is required to assess the efficacy of this device.
    European Journal of Vascular and Endovascular Surgery 05/2007; 33(4):408-11. DOI:10.1016/j.ejvs.2006.10.019 · 2.49 Impact Factor
  • Peter R F Bell ·

    Vascular 02/2007; 15(1):1-2. DOI:10.2310/6670.2007.00001 · 0.80 Impact Factor
  • Matthew J Bown · Guy Fishwick · Robert D Sayers · Peter R.F. Bell ·
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    ABSTRACT: Emergency EVR for ruptured AAA is now technically feasible, and several reports with small numbers have appeared in the literature from major centers suggesting that the results may be the same as or better than seen with open repair. The immediate priority is avoidance of over-resuscitation together with the rapid transfer of the patient to CT and then to the operating theater. Because of the learning curve involved, these cases should be attempted only by major centers that have extensive elective endovascular experience. The requirement for 24-hour availability of surgeons and radiologists trained in endovascular techniques places an enormous strain on vascular and radiologic staff and is achievable only in major centers with large teams of doctors. These issues raise important questions about the delivery of vascular services and whether all cases of ruptured aortic aneurysm should be transferred to major vascular centers. The operating theater staff and other support persons need training in endovascular techniques and in rapid deployment of an aortic occlusion balloon. A wide selection of devices, guidewires, and catheters must be immediately available in the operating theater. The ideal way to establish the role of EVR for ruptured AAA would be a randomized trial, but there might be logistic difficulties in recruiting sufficient numbers in major vascular centers, particularly as screening for AAA becomes more common and reduces the number of cases. There also are ethical issues as to whether these patients can give informed consent for involvement in such a trial. The alternative is for major centers to continue to develop their endovascular programs, to do more cases, and to compare the results with historical controls undergoing open repair.
    Advances in Surgery 02/2007; 41:63-80. DOI:10.1016/j.yasu.2007.05.005
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    ABSTRACT: Because subintimal angioplasty (SA) is a technique that can achieve recanalization of long arterial occlusions, it is considered an alternative to lower limb bypass operations. The aim of this prospective study was to identify the risk factors that affect patency of SA in patients suffering from critical limb ischemia (CLI). 51 consecutive infrainguinal SA were done in 46 patients suffered from CLI. The patients were followed-up with regular duplex scans up to 12 months post-intervention. Sex, atherosclerosis risk factors, and some technical details of the procedure (number of patent run-off vessels after the procedure, length and re-entry point of angioplasty) were examined as potential risk factors of patency, using survival analysis statistical techniques. The overall patency rate at 12 months post-intervention was 50%. According to Cox-regression analysis, the factors that affect patency were the number of run-off vessels and the length of occlusion. Patients with two or three run-off vessels had a hazard of occlusion of 0.30 (P = .027) compared to those who had one run-off vessel. The 12-months patency in patients with more than one run-off vessels was 81% vs. 25% in patients with one run-off vessel. Regarding the length of angioplasty, the hazard of reocclusion was 1.02 for every centimeter of occlusion (P = .049). The number of patent run-off crural vessels after the angioplasty and the length of occlusion are significant risk factors for reocclusion of infrainguinal SA in patients with CLI. Trying to recanalize more than one run-off vessels could raise the SA patency.
    European Journal of Vascular and Endovascular Surgery 01/2007; 32(6):668-74. DOI:10.1016/j.ejvs.2006.07.016 · 2.49 Impact Factor
  • DA Payne · P D Hayes · A Bolia · G Fishwick · P R F Bell · AR Naylor ·
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    ABSTRACT: This was a retrospective study of the effectiveness of open, retrograde angioplasty/stenting of supra-aortic arterial stenoses combined with transcranial Doppler-directed dextran therapy in preventing perioperative embolization. Eight patients underwent angioplasty/stenting of the proximal common carotid (synchronous carotid endarterectomy (CEA) in six), while four underwent angioplasty/stenting of the innominate artery (synchronous CEA in one). Open exposure of the carotid bifurcation enabled temporary carotid clamping to protect the brain from procedural embolization. Dextran was administered to patients with a high rate of embolization on transcranial Doppler after the operation. No emboli were recorded in the cerebral circulation during the actual angioplasty procedure when the internal carotid artery was clamped. After operation three patients developed high-rate embolization and received dextran. No strokes or deaths occurred within 30 days of treatment. One patient developed symptoms and a recurrent stenosis greater than 50 per cent during follow-up and was treated by redo angioplasty. Retrograde angioplasty/stenting with or without synchronous CEA offers an alternative approach to treating patients with supra-aortic inflow disease.
    British Journal of Surgery 02/2006; 93(2):187-90. DOI:10.1002/bjs.5232 · 5.54 Impact Factor
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    ABSTRACT: Abdominal aortic aneurysm (AAA) expansion is characterized by extracellular matrix degradation and widespread inflammation. In contrast, the processes that characterize AAA rupture are not well understood. The aim of this study was to investigate the proteolytic and cellular activity of ruptured AAA, focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). Anterior aneurysm wall biopsies were taken from 55 nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies, MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies compared with their 12 paired anterior wall biopsies, whereas other MMPs and TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9 expression was mediated by native mesenchymal cells and was independent of the inflammatory infiltrate. A localized increase in MMP-8 and -9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.
    Circulation 01/2006; 113(3):438-45. DOI:10.1161/CIRCULATIONAHA.105.551572 · 14.43 Impact Factor
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    J M Laurence · M J McCarthy · N J M London · P R F Bell · AR Naylor ·
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    ABSTRACT: In this centre, angiography is used only in selected cases, whilst duplex ultrasound (DU) is the main imaging method prior to carotid endarterectomy (CEA). DU has no associated morbidity and so can be repeated immediately before surgery to detect changes in the carotid plaque or degree of stenosis. We retrospectively examined our Vascular Surgery Audit database for the last 500 patients admitted for CEA. In each case, the DU scan was repeated immediately before surgery. From 500 admissions, repeat DU immediately prior to surgery detected 8 (1.6%) situations where CEA would no longer have been an appropriate intervention. In four cases, the degree of stenosis was found to be less than 70% on the repeat scan - in three cases the internal carotid artery (ICA) had occluded or sub-occluded and in one case there was a dissection of the ICA plaque. DU can be repeated, with no associated morbidity, immediately prior to surgery. Such a practice changes management decisions in 1.6% of admissions for CEA, allowing surgery unjustified by current evidence to be avoided. This policy also serves several other important purposes: it is a method of internal validation, provides a means of improving training of vascular technologists and of achieving quality assurance in DU techniques.
    Annals of The Royal College of Surgeons of England 12/2005; 87(6):443-4. DOI:10.1308/003588405X60588 · 1.27 Impact Factor

Publication Stats

11k Citations
2,467.13 Total Impact Points


  • 1976-2009
    • University of Leicester
      • • Department of Cardiovascular Sciences
      • • Ophthalmology Group
      Leiscester, England, United Kingdom
  • 1994-2003
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2002
    • University Hospitals Coventry and Warwickshire NHS Trust
      Coventry, England, United Kingdom
  • 1996-1997
    • Utrecht University
      Utrecht, Utrecht, Netherlands
    • Cedars-Sinai Medical Center
      • Cedars Sinai Medical Center
      Los Angeles, CA, United States
    • Royal Devon and Exeter NHS Foundation Trust
      Exeter, England, United Kingdom
  • 1981
    • University College London
      • Division of Medicine
      Londinium, England, United Kingdom
  • 1973-1976
    • University of Glasgow
      Glasgow, Scotland, United Kingdom