P R Bell

University of Leicester, Leiscester, England, United Kingdom

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Publications (481)2115.8 Total impact

  • Article: Vascular 03
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    ABSTRACT: Matrix metalloproteinases (MMPs) play an important part in the expansion of abdominal aortic aneurysms (AAA). It has been suggested that MMPs appear to be present in differing concentrations during the progression of aneurysm development. Our aim was to determine the MMP profiles in tissue from aneurysms of differing sizes, to define whether rupture results from gradual widespread increases in proteolytic capacity, or is confined to a localized area of the aortic wall. Samples of anterior aortic wall were obtained from 81 patients undergoing elective AAA repair (n = 59, median age 72 years, diameter 6 cm), or emergency repair of ruptured AAA (rAAA) (n = 22, age 72). The elective group was divided by aneurysm size into 2 groups; medium sized (5–6.5 cm, n = 31, age 70) and large (>6.5 cm, n = 11, age 73). Paired samples of aortic sac were obtained from the sac and the site of aortic rupture from nine patients with rAAA (age 70). MMPs-1, -2, -3, -9, and -13, and TIMPs-1 and -2 were extracted from the tissue specimens and quantified using ELISA. There were no significant differences in MMP and TIMP levels in AAA sac of medium and large sized aneurysms, or ruptured and nonruptured AAA sac. In paired specimens taken from rAAA, MMP-9 was seven times higher at the site of rupture than in the anterior sac (98.57 ng mg−1[IQR 56.02–134.5]versus 13.89 ng mg−1[7.80–46.81], P = 0.012). These data demonstrate that MMP profiles vary little with expansion of the aneurysm in medium- and large-sized aneurysms. Rupture is likely to be a result of localized elevations in MMP-9 and this would be an appropriate target for pharmacotherapy.
    British Journal of Surgery 01/2009; 89(S1):33 - 33. · 4.84 Impact Factor
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    ABSTRACT: Background: Rupture of an abdominal aortic aneurysm (AAA) carries a mortality rate of up to 90%. Matrix metalloproteinases (MMPs) play a fundamental role in aneurysm formation. Previous studies have suggested a systemic increase in proteolysis in patients with AAAs and MMPs have been shown to be elevated in the serum of these patients. However, no study as yet has demonstrated differences in asymptomatic and ruptured aneurysms. The aim of the study was to determine the MMP profiles of serum from patients presenting for elective and emergency aneurysm repair.Methods: Samples of venous blood were obtained intraoperatively from 61 patients undergoing elective repair of nonruptured AAA (n = 50, median age 71 years), or emergency repair (n = 11, age 72) of ruptured AAA. Serum was quantified for the concentration of MMPs-1, -2, -3, -9, -13, TIMP-1 and -2 utilizing ELISA.Results: There were no significant differences in MMPs-2,-3,-13 and TIMP levels in the serum of patients with nonruptured and ruptured AAA. Serum MMP-1 levels were significantly increased in rupture (10.36 ng mL−1[IQR 5.94–15.94]versus 24.81 ng mL−1[18.14–41.39], P < 0.0001). MMP-9 levels were six times higher in serum from ruptured compared with nonruptured AAA patients (19.13 ng mL−1[9.27–34.24]versus 117.9 ng mL−1[30.43–161.8], P = 0.0015).Conclusions: These data demonstrate that the serum MMP profile of patients with ruptured aneurysms is significantly different to patients with nonruptured AAA. Extension of these data may allow prediction of rupture rates from serum MMP levels.
    British Journal of Surgery 01/2009; 89(S1):15 - 15. · 4.84 Impact Factor
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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. · 2.82 Impact Factor
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    ABSTRACT: To investigate the distraction forces affecting grafts used to treat abdominal aortic aneurysms in an in vitro model. Using a standard cardiac pump and a rigid plastic circulation system, distraction forces were measured with a gramometer attached to a PTFE graft while the pressure inside a rigid aortic sac was varied. If the pressure in the 'aneurysm sac' is maintained at the same level as the systemic pressure, the displacement force is zero. The displacement force is affected adversely by the level of systemic pressure, as this rises the displacement forces rise in an almost linear fashion. These observations may have important consequences for stent graft design and use in vivo pressurisation of a sealed sac may therefore not necessarily be an adverse event. Systemic hypertension is obviously important and its control may be necessary to prevent graft migration.
    European Journal of Vascular and Endovascular Surgery 01/2004; 26(6):596-601. · 2.82 Impact Factor
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    ABSTRACT: Outcomes after synchronous carotid endarterectomy (CEA) plus coronary artery bypass (CABG) relative to surgical and patient based variables. Systematic review of 94 published series (7863 synchronous procedures). 11.5% of patients died or suffered a stroke/myocardial infarction in the peri-operative period (95% CI 10.1-12.9). The risk of death/stroke appeared to significantly diminish in studies published between 1993-2002, compared with 1972-1992 (7.2% (95% CI 6.5-9.1) versus 10.7% (95% CI 8.9-12.5), p = 0.03). However, increasing operative experience was not associated with significantly lower risks of death/stroke; (1-49 cases (9.6% (95% CI 7.5-11.8); 50-99 cases (9.1% (95% CI 6.4-11.8); 100+ cases (8.4% (95% CI 6.9-10.1) (p = 0.64)). Patients with severe bilateral carotid disease were significantly more likely to suffer death and/or stroke compared to patients with unilateral disease (odds ratio 2.5, 95% CI 1.4-5.0, p = 0.001). Similarly, patients with a prior history of stroke/transient ischaemic attack (TIA) were significantly more likely to suffer a further stroke than asymptomatic patients (odds ratio 1.8, 95% CI 1.1-2.8, p = 0.008). There was no difference in the risk of death/stroke relative to the timing of CEA (pre- versus on-cardiopulmonary bypass), but recent small studies indicate that improved outcomes might be achieved by performing CABG 'off-bypass'. Synchronous CEA + CABG is associated with a not insignificant cardiovascular risk. No comparable information is available for similar patients undergoing CABG without prophylactic CEA.
    European Journal of Vascular and Endovascular Surgery 10/2003; 26(3):230-41. · 2.82 Impact Factor
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    ABSTRACT: Elevated intra-abdominal pressure (IAP) may cause widespread organ dysfunction (abdominal compartment syndrome) through effects on the respiratory, cardiac, renal and gastro-intestinal systems. The aim of this study was to document IAP following aneurysm surgery, and to determine the effect of IAH on outcome. Prospective observational study. University Hospital. The patient cohort comprised 75 patients undergoing infra-renal aneurysm repair (53 non-ruptured [40 conventional--1 death, 13 endovascular] and 22 conventionally repaired ruptured AAA--8 deaths). IAP was quantified by bladder manometry at the termination of the procedure and at 24 h intervals in patients who remained intubated. Physiological indices of organ function were recorded. Statistical analysis utilized the unpaired t-test, Fischer's exact test and Pearson's correlation. IAP was significantly higher at abdominal closure following ruptured aneurysm repair (15.4 mmHg [SE 1.6]) than conventional (10.5 [0.89]) or endovascular elective repair (6.4 [1.0]) of non-ruptured AAA. The sensitivity and specificity of IAP to predict subsequent mortality was analysed using a receiver characteristic operating curve. This analysis demonstrated that a cut off of 15 mmHg was the most useful for indicating patients at risk (sensitivity 0.66, specificity 0.79). Physiological indices of organ dysfunction (pH[P = 0.027], base excess [p = 0.005], peak inspiratory pressure [p = 0.0015], CVP and urine output [p = 0.0029]) were significantly impaired in patients with IAP > or = 15 mmHg, in comparison to patients with lower pressures. IAP correlated significantly with indices of cardiac (CVP p = 0.038), respiratory (PaO2/FiO2, p = 0.026), and renal function (urine output p = 0.046). These data suggest that the management of IAH may have a role following repair of ruptured AAA. High intra-abdominal pressures rarely complicate elective or endovascular aneurysm repair.
    European Journal of Vascular and Endovascular Surgery 09/2003; 26(3):293-8. · 2.82 Impact Factor
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    ABSTRACT: Background:In a previous study performed at this centre (1994–1997) to document the impact of instituting an endovascular programme, the mortality rate for elective infrarenal aneurysm repair was unacceptable (16 per cent). In an attempt to reduce this complication rate, two fundamental changes in practice were instituted. First, patients were selected and counselled for operation on the basis of a physiological scoring system, POSSUM (Physiological and Operative Surgical Score for the enUmeration of Mortality and morbidity). Second, patients were admitted to the critical care unit for at least 3 days after operation, before discharge to the ward. The aim of the study was to audit the result of these changes.Methods:Data were collected prospectively for all patients admitted for elective aneurysm repair between November 1998 and January 2000. POSSUM score, postoperative mortality and morbidity, and intensive care unit (ITU) or high dependency unit stay were compared between historical controls (1994–1997) and operations performed after the change in practice.Results:The results are tabulated below as median values. Historical study (n = 104)Present study (n = 47)P†*χ2and Mann–Whitney U testsPOSSUM19180·268ITU stay (days)1·03·0< 0·001Mortality rate (%)164< 0·001Morbidity rate (%)2817< 0·001Unplanned ITU return811< 0·001Comparison between the two groups demonstrated that after changes in referral practice, the perioperative mortality rate improved significantly from 16 to 4 per cent. Comparison of the patient cohorts demonstrated no significant differences in preoperative physiological status.Conclusion:These data demonstrate that defined changes in the perioperative management of patients undergoing elective aneurysm surgery may favourably affect mortality. As there was no difference in POSSUM scores between the two groups, it is likely that the improved outcome reflects more intensive postoperative care. © 2001 British Journal of Surgery Society Ltd
    British Journal of Surgery 12/2002; 88(4):615 - 616. · 4.84 Impact Factor
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    ABSTRACT: Background:The platelet adenosine 5′-diphosphate (ADP) receptor antagonist clopidogrel has proved an effective antiplatelet agent in the prevention of arterial thrombosis. In the vast majority of studies clopidogrel has been used as an alternative to aspirin, but the widespread use of aspirin, and the different modes of actions of the two drugs, makes it important to determine the safety and efficacy of using both drugs in combination. This study reports the effect of this drug combination on bleeding times and platelet function in humans.Methods:The study was conducted in normal, healthy subjects to evaluate the effects of different doses of clopidogrel on bleeding time, platelet aggregation and activation, above a baseline of standard aspirin therapy. Seven normal men (mean age 30 years) were given aspirin (150 mg) for 3 days. Subjects received clopidogrel (75 mg) at 24 and 48 h, followed by a third dose of clopidogrel (300 mg) on day 3.Results: BaselineAspirin aloneAspirin + low-dose clopidogrelAspirin + high-dose clopidogrelBleeding time (min)5·17·517·524·9Aggregation in response to ADP (%)72483525Fibrinogen binding in response to ADP (%)64504024The combination of aspirin plus clopidogrel leads to a significant reduction in platelet function relative to aspirin alone (P < 0·05), and is associated with a significant increase in the bleeding time (P < 0·05). The response to collagen was similarly affected. Platelet fibrinogen binding in response to both ADP and thrombospondin-related adhesive protein was reduced only partially by aspirin, but significantly reduced by both doses of clopidogrel (P < 0·05 for all). P-selectin expression in response to both agonists was also reduced, but not significantly. Basal levels of fibrinogen binding, P-selectin, glycoprotein (GP) IIb–IIIa and GPIb expression were not affected by treatment.Conclusion:Blocking both the cyclo-oxygenase and ADP pathways of platelet activation has a profound effect on platelet response to agonists, which may offer significant potential benefit in preventing thrombotic events relative to aspirin alone. Achieving the correct balance between haemostasis and thrombosis with these useful agents will require further study. © 2001 British Journal of Surgery Society Ltd
    British Journal of Surgery 12/2002; 88(4):613 - 614. · 4.84 Impact Factor
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    ABSTRACT: Blood pressure instability after carotid endarterectomy (CEA) has been associated with a disturbance of the baroreflex control mechanism caused by the surgery in the carotid sinus region. The purpose of this study was to determine if a deterioration in carotid baroreceptors occurs during the surgery. Heart rate (HR) and blood pressure (BP) were recorded continuously in 60 patients undergoing CEA as well as preoperatively and postoperatively at 2 days and 6 weeks. The baroreflex sensitivity was determined by cross-spectral analysis of HR and systolic blood pressure (SBP). During the surgery, three tests were used to assess the baroreflex response. The first test simulated a sudden fall in systemic blood pressure by clamping the common carotid artery. The second test simulated a rise in systemic blood pressure by applying pressure by using a rubbing action on the luminal surface of the carotid sinus region. The rub test was performed twice, once with the atheromatous plaque in situ and once when the plaque had been removed. The third test is clamp removal and restoration of blood flow through the carotid sinus. Carotid cross-clamping increased mean +/- standard error of the mean SBP from 117 +/- 3 mm Hg before clamping to 125 +/- 3 mm Hg (P <.05) at 30 beats after clamping. The first rub test with the plaque in situ decreased SBP from 121 +/- 3 mm Hg to 117 +/- 3 mm Hg (P <.01) at 10 beats after the rub test, indicating a functioning baroreceptor reflex. The second rub test increased SBP from 126 +/- 3 mm Hg to 128 +/- 3 mm Hg (P <.05). SBP dropped (P <.01) when unclamping suggesting a selective alteration of the baroreflex sensitivity. The baroreflex sensitivity was significantly reduced 2 days postoperatively when compared to preoperative values (P <.05). These findings suggest that the act of plaque removal could be associated with a partial disruption of baroreceptor mechanism in the carotid artery. This could affect type I baroreceptors.
    Journal of Vascular Surgery 10/2002; 36(4):793-8. · 2.88 Impact Factor
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    ABSTRACT: abdominal aortic aneurysms (AAA) are associated with excessive vascular matrix remodelling. Recent findings suggest a systemic overproduction of matrix metalloproteinases-2 (MMP-2) by vascular smooth muscle cells (SMC) may be pivotal aetiologically. SMC migration is facilitated by MMP mediated proteolysis of the basement membrane and extracellular matrix. Our aim was to see if enhanced MMP-2 production by these SMC exhibit increased invasion, in an in vitro model of migration. SMC were derived from inferior mesenteric vein (IMV) harvested from patients undergoing aneurysm repair (n=6) or colectomy for diverticulosis (n=6, control). Using a modified Boyden chamber chemotaxis was measured towards platelet derived growth factor (PDGF) and foetal calf serum (FCS) and invasion through a Matrigel layer. MMP-2 production was quantified by ELISA and gelatin zymography. chemoattractant studies demonstrated no difference in the effect of PDGF or FCS between the two populations of SMC. However, invasive studies demonstrated a significant increase in the number of migrating SMC isolated from IMV of AAA patients. Analysis of culture media extracts revealed that this difference was associated with a significant increase in production of MMP-2. SMC derived from patients with AAA demonstrate increased invasive properties when compared to a control group. Increased migration appears to be due to overproduction of MMP-2. The enhanced migratory potential of these SMC may lead to extracellular matrix remodelling and subsequent medial disruption demonstrated in the aneurysmal aorta. These data further support evidence of the proteolytic role of MMP-2 in cell migration.
    European Journal of Vascular and Endovascular Surgery 08/2002; 24(1):72-80. · 2.82 Impact Factor
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    Annals of The Royal College of Surgeons of England 06/2002; 84(3):215; author reply 215. · 1.33 Impact Factor
  • The Lancet 01/2002; 358(9297):1999-2000. · 39.06 Impact Factor
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    ABSTRACT: There is limited understanding of the reasons underlying post-CEA carotid thrombosis. Clinicians have often implicated operative technique, such as patch type or shunting, however the evidence for this is limited. We have studied whether it is the patients themselves who are prothrombotic, by studying the rates of emboli detection in patients undergoing bilateral CEAs at separate time points. Sixteen patients (3 women) underwent CEA during the study period, all of whom were taking aspirin. CEA was performed in a standardised manner throughout the study. All patients were monitored for 3 h postoperatively using a 2 MHz fixed head probe. Those patients who had no emboli detected on TCD after the first operation, had a mean of 2.5 emboli after the second operation. Patients with emboli after the first operation had a mean of 41.3 emboli after the second CEA (MWU test, p=0.02). The dose of aspirin administered did not affect emboli rates. Correlation of the number of emboli detected after the first CEA with the second CEA gave a significant correlation ( p=0.038). There appear to be factors relating to the patient that places some individuals at an increased risk of thrombotic stroke. Further elucidation of these factors may enable more effective, targeted therapy to be applied in the prevention of arterial thrombosis.
    European Journal of Vascular and Endovascular Surgery 01/2002; 22(6):496-8. · 2.82 Impact Factor
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    ABSTRACT: Multiple organ failure is a common mode of death following abdominal aortic aneurysm repair, particularly after rupture. Cytokines are the principal mediators of the inflammatory response to injury and high levels of circulating cytokines have been associated with poor outcome in major trauma and sepsis. Abdominal aortic aneurysm repair results in an ischaemia-reperfusion injury to the tissues distal to the site of aortic clamping. The inflammatory response in these tissues causes the release of cytokines, principally Interleukins 1-beta, 6, and 8, and Tumour Necrosis Factor alpha. If released in large enough concentrations, these cytokines may enter the circulation and gain access to organs distant to the site of initial injury. Circulating cytokines cause dysfunction of the renal, cardiovascular, respiratory, nervous and musculo-skeletal systems. The combination of these individual changes in organ function is the multiple-organ dysfunction syndrome, which may progress to multiple organ failure.
    European Journal of Vascular and Endovascular Surgery 01/2002; 22(6):485-95. · 2.82 Impact Factor
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    ABSTRACT: Aims: Elevated intra-abdominal pressure (IAP) may cause widespread organ dysfunction (abdominal compartment syndrome) through effects on the respiratory, cardiac, renal and gastro-intestinal systems. The aim of this study was to document IAP following aneurysm surgery, and to determine the effect of IAH on the outcome.Methods: The patient cohort comprised 66 patients undergoing infra-renal aneurysm repair (45 nonruptured (32 conventional, 1 death; 13 endovascular); 21 ruptured AAA, 8 deaths). IAP was quantified at the termination of the procedure and 24 h postoperatively. Physiological indices of organ function were recorded, as were the levels of TNF- and IL-6.Results: IAP was significantly higher at abdominal closure following ruptured aneurysm repair (15.4 mmHg [SE 1.6]) than conventional (10.5 [0.89]) or endovascular repair (6.4 [1.0]) of nonruptured AAA. The sensitivity and specificity of IAP to predict subsequent mortality was analysed using a receiver characteristic operating curve. This analysis demonstrated that a cut off of 15 mmHg was most useful for indicating patients at risk (sensitivity: 0.66; specificity: 0.79). Physiological indices of organ dysfunction (pH [0.027], base excess [0.005], peak inspiratory pressure [0.0015], CVP and urine output [0.0029]) were significantly impaired in patients with IAP > 15 mmHg in comparison to patients with lower pressures. Similarly, IAP correlated significantly with the concentrations of IL-6 (0.0075) and TNF- (0.0025), as well as with indices of cardiac (CVP 0.038), respiratory (PaO2/FiO2 = 0.026), and renal function (urine output = 0.046).Conclusions: These data suggest that the management of IAP may have a role following repair of ruptured AAA.
    British Journal of Surgery 12/2001; 89(S1):72 - 72. · 4.84 Impact Factor
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    ABSTRACT: To investigate the prevalence of MRSA infection in patients treated in a major vascular unit and examine its consequences. A retrospective case-note review was performed. During the period 1993 to 2000, a total of 172 patients (4.4% of total) were positive for MRSA. Of these 97 were colonised and 75 were infected by MRSA. The proportion of wound or graft infections caused by MRSA has increased (4% in 1994 to 63% in 2000). Three patients developed native artery infection (one following aortic stent insertion and 2 following embolectomy). All patients with aortic graft infection died. All patients with infected prosthetic infrainguinal bypass ended up with an amputation. The prevalence of MRSA infection is increasing. Infection of aortic grafts appears to be uniformly fatal and lower limb graft infection is associated with high limb loss.
    European Journal of Vascular and Endovascular Surgery 10/2001; 22(3):211-4. · 2.82 Impact Factor
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    ABSTRACT: Patients with abdominal aortic aneurysms (AAAs) exhibit arterial dilation and altered matrix composition throughout the vasculature. Matrix metalloproteinase-2 (MMP-2) is the dominant elastase in small AAAs, and overexpression of MMP-2 in vascular smooth muscle cells (SMCs) may be a primary etiological event in aneurysm genesis. The aim of this study was to investigate MMP-2 production in vascular tissue remote from the abdominal aorta. Inferior mesenteric vein (IMV) was harvested from patients undergoing aneurysm repair (n=21) or colectomy for diverticular disease (n=13, control). Matrix composition of the vessels was determined by stereological techniques. MMPs were extracted from tissue homogenates and quantified by gelatin zymography and ELISA. MMP-2, membrane type-1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinases type 2 (TIMP-2) expression were determined by Northern analysis. SMCs were isolated from IMV, and the production and expression of MMP-2 and TIMP-2 in the SMC lines were quantified. Tissue homogenates and isolated inferior mesenteric SMCs from patients with aneurysms demonstrated significantly elevated MMP-2 levels, with no difference in TIMP-2 or MT1-MMP. These differences were a result of increased MMP-2 expression. Histological examination revealed fragmentation of elastin fibers within venous tissue obtained from patients with AAA and a significant depletion of the elastin within the media. In situ zymography localized elastolysis to medial SMCs. Patients with AAA have elevated MMP-2 levels in the vasculature remote from the aorta. This finding is due to increased MMP-2 expression from SMCs, a characteristic maintained in tissue culture. These data support both the systemic nature of aneurysmal disease and a primary role of MMP-2 in aneurysm formation.
    Circulation 08/2001; 104(3):304-9. · 15.20 Impact Factor
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    ABSTRACT: A recent overview indicated that although routine patching is safer than routine primary closure after carotid endarterectomy (CEA), there is no systematic evidence that patch type influences outcome. However, most surgeons still believe that prosthetic patches are probably more thrombogenic than vein patches. This study tested the hypothesis that there was no difference in thrombogenicity between the different patch types. A total of 274 patients undergoing 276 CEAs were randomized to either Dacron-patch closure (n = 137) or vein-patch closure (n = 139). All patients with an accessible cranial window were monitored for 3 hours postoperatively with transcranial Doppler scanning (TCD). The number of emboli and rate of embolization were quantified with the requirement for selective dextran therapy to control high rates of postoperative embolization. All patients were assessed postoperatively and again at 30 days by a neurologist, and all patients underwent a duplex examination at 30 days. The 30-day death/any stroke rate was 2.2% for patients in the Dacron-patch group and 3.6% for patients in the vein-patch group (P =.72). Patients in the Dacron-patch group had a higher incidence of postoperative emboli (median, 5; interquartile range, 0-10.5) than patients in the vein-patch group (median, 3; interquartile range, 1-17; P =.028). However, the incidence of detecting more than 50 emboli was virtually identical, and patch type had no effect on the incidence of high-rate, sustained embolization that required dextran therapy (5.3% for Dacron, 3.7% for vein). No patient had a carotid thrombosis at 30 days. Sustained, high-rate embolization, previously shown to be highly predictive of progression to carotid thrombosis, appears to be patient dependent, rather than related to patch type.
    Journal of Vascular Surgery 06/2001; 33(5):994-1000. · 2.88 Impact Factor
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    ABSTRACT: Recent reports suggest that apoptosis resulting from the disruption of the normal cell-matrix relationship (anoikis) during islet isolation could lead to a loss of islet tissue in culture. Insulin is known to have a role in cell growth and survival, and this study was undertaken to assess any beneficial effect on islets by supplementing the islet culture medium with insulin. Human and porcine islets were cultured in medium supplemented with 0, 10, 100, and 1,000 ng x mL(-1) insulin. Secretory function was assessed by perifusion at days 1 and 8. The results demonstrated a significant variation in stimulation index between isolations for human islets, but there was no effect relating to the concentration of insulin in the medium or time in culture. For porcine islets, there was a significant (p < 0.001) improvement in secretory function for islets cultured in 10 and 100 ng x mL(-1) insulin, relative to 0 and 1,000 ng x mL(-1) insulin. There was no interisolation variation or effect of time in culture. In conclusion, the secretory function of porcine islets benefited from the addition of 10 to 100 ng x mL(-1) insulin to the culture medium, but interisolation variation in human islet secretory function did not allow any specific effect of the insulin to be determined.
    Pancreas 02/2001; 22(1):72-4. · 2.95 Impact Factor
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    ABSTRACT: Carotid bifurcation angioplasty and stenting (CBAS) has generated controversy and widely divergent opinions about its current therapeutic role. To resolve differences and establish a unified view of CBAS' present role, a consensus conference of 17 experts, world opinion leaders from five countries, was held on November 21, 1999. These 17 participants had previously answered 18 key questions on current CBAS issues. At the conference these 18 questions and participants' answers were discussed and in some cases modified to determine points of agreement (consensus), near consensus, (prevailing opinion), or divided opinion (disagreement). Conference discussion added two modified questions, placing a total of 20 key questions before the participants, representing four specialties (interventional radiology, seven; vascular surgery, six; interventional cardiology, three; neurosurgery, one). It is interesting that consensus was reached on the answers to 11 (55%) of 20 of the questions, and near consensus was reached on answers to 6 (30%) of 20 of the questions. Only with the answers to three (15%) of the questions was there persisting controversy. Moreover, both these differences and areas of agreement crossed specialty lines. Consensus Conclusions: CBAS should not currently undergo widespread practice, which should await results of randomized trials. CBAS is currently appropriate treatment for patients at high risk in experienced centers. CBAS is not generally appropriate for patients at low risk. Neurorescue skills should be available if CBAS is performed. When cerebral protection devices are available, they should be used for CBAS. Adequate stents and technology for performing CBAS currently exist. There were divergent opinions regarding the proportions of patients presently acceptable for CBAS treatment (<5% to 100%, mean 44%) and best treated by CBAS (<3% to 100%, mean 34%). These and other consensus conclusions will help physicians in all specialties deal with CBAS in a rational way rather than by being guided by unsubstantiated claims.
    Journal of Vascular Surgery 02/2001; 33(2 Suppl):S111-6. · 2.88 Impact Factor

Publication Stats

7k Citations
2,115.80 Total Impact Points

Institutions

  • 1980–2009
    • University of Leicester
      • Department of Cardiovascular Sciences
      Leiscester, England, United Kingdom
  • 2007
    • Attikon University Hospital
      Athínai, Attica, Greece
  • 1999–2002
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • Glasgow Caledonian University
      • Division of Biomedical Sciences
      Glasgow, SCT, United Kingdom
  • 1997–2002
    • University Hospitals Of Leicester NHS Trust
      • Department of Surgery
      Leiscester, England, United Kingdom
  • 2000
    • Oxford Brookes University
      Oxford, England, United Kingdom
  • 1993
    • University of Nottingham
      Nottigham, England, United Kingdom
  • 1991
    • Duke University Medical Center
      Durham, North Carolina, United States
  • 1989
    • University General Hospital
      Houston, Texas, United States
  • 1986
    • Aarhus University
      Aarhus, Central Jutland, Denmark
  • 1974
    • University of Glasgow
      Glasgow, Scotland, United Kingdom