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Biomedical subjects

P R F Bell

Publications and source records attributed to P R F Bell.

At least 19 recordsLinked to original sources

Intravascular stapler for "open" aortic surgery: preliminary results.

OBJECTIVES: The aim of this study was to assess the efficacy of a new stapling device using a pig model. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Anastomosis, Surgical↗

Cerebral protection during open retrograde angioplasty/stenting of common carotid and innominate artery stenoses.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Retrograde angioplasty/stenting with or without synchronous CEA offers an alternative approach to treating patients with supra-aortic inflow disease.

Adult↗

Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm.

BACKGROUND: Loss of elastin is the initiating event in abdominal aortic aneurysm (AAA) formation, whereas loss of collagen is required for continued expansion. The elastolytic matrix metalloproteinases (MMPs) 2 and 9 are well described, but the source of excessive collagenolysis remains undefined. The aim of this study was to determine the expression of MMP-8, a potent type I collagenase, in normal aorta and AAA. METHODS: Infrarenal aortic biopsies were taken from 40 AAA and ten age-matched normal aortas. The concentrations of MMP-8 protein and its inhibitors, tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-2, were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was used to localize MMP-8 expression. RESULTS: MMP-8 concentrations were significantly raised in AAA compared with normal aorta (active MMP-8: 4.5 versus 0.5 ng per mg protein, P < 0.001; total MMP-8: 16.6 versus 2.8 ng per mg protein, P < 0.001). Levels of TIMP-1 and TIMP-2 were significantly lower in AAA than in normal aortic samples (TIMP-1: 142.2 versus 302.8 ng per mg protein; P = 0.010; TIMP-2: 9.2 versus 33.1 ng per mg protein, P < 0.001). Immunohistochemistry localized MMP-8 to mesenchymal cells within the adventitia of the aortic wall. CONCLUSION: The high concentration of MMP-8 in aortic aneurysms represents a potent pathway for collagen degradation, and hence aneurysm formation and expansion.

Aged↗

Patch corrugation on duplex ultrasonography may be an early warning of prosthetic patch infection.

Four of 10 patients presenting with prosthetic patch infection after carotid endarterectomy (CEA) were noted to have Duplex evidence of 'corrugation' of the prosthetic patch, without false aneurysm formation. In three, corrugation preceded diagnosis of overt patch infection by up to 11 months. In the fourth patient, awareness of the potential significance of patch corrugation enabled timely treatment of an otherwise unrecognized patch infection. Even if other imaging modalities are normal, the presence of patch corrugation on Duplex should prompt the surgeon to (at least) consider the possibility of patch infection.

Aged↗

HMG-CoA reductase inhibitors (statins) decrease MMP-3 and MMP-9 concentrations in abdominal aortic aneurysms.

BACKGROUND: An imbalance in matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in AAA formation. 3-Hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) are known to reduce MMP levels. The aim of this study was to investigate the in vivo effect of statins on MMP levels in AAA. METHODS: Infra-renal aortic biopsies were obtained from the anterior sac of 63 patients undergoing asymptomatic repair. Seventeen patients were taking a statin pre-operatively, while 46 were not. The concentrations of MMP-1, -2, -3, -8, -9, -13, TIMP-1 and TIMP-2 were quantified using ELISA. RESULTS: There was no difference in the concentration of MMP-1, -2, -8, -13, TIMP-1 or -2 in patients taking versus not taking a statin pre-operatively. In contrast levels of MMP-9 and MMP-3 were significantly lower in patients taking a statin. CONCLUSIONS: These data demonstrate that statins decrease MMP-9 and MMP-3 levels and represent a potential pharmacotherapy in established AAA.

Aged↗

A comparison of methods for determining genotypes at the tumour necrosis factor-alpha-308, interleukin (IL)-1beta+3953, IL-6 -174 and IL-10 -1082/-819/-592 polymorphic loci.

Induced heteroduplex genotyping (IHG) is one of many methods that can be used to determine single nucleotide polymorphisms (SNPs). It is relatively new in comparison to other polymerase chain reaction (PCR)-based techniques. The aim of this study was to compare the results of genotyping using IHG with the results of genotyping using either polymerase chain reaction-sequence-specific primers (PCR-SSP) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for SNPs in the tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10 genes. Ninety patients who consented to participate in the study had their genotypes determined by IHG and either PCR-SSP (TNF-alpha-308 and IL-10 -1082/-819/-592) or PCR-RFLP (IL-1beta +3953 and IL-6 -174). Results for each locus were compared between techniques by calculating the Kappa statistic as a measure of agreement. The IHG and more traditional genotyping methods produced very similar results at all loci. The Kappa statistics for each locus were as follows: TNF-alpha -308, K = 0.727; IL-1beta +3953, K = 0.886; IL-6 -174, K = 0.909; IL-10 -1082, K = 0.876; IL-10 -592, K = 0.920. IHG is a valid method for the determination of genotypes at the loci examined in this study and produces comparable results to those of more traditional methods of genotyping.

Cytokines↗

Duplex imaging immediately prior to carotid endarterectomy.

INTRODUCTION: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Carotid Artery, Internal↗

Impact of the volume of aneurysmal contents on intraaneurysmal pressure after endovascular grafting (experimental studies).

With the purpose of clarifying the nature and outlining certain constituents of such an undesirable condition designated as "endotension", that emerges after transluminal grafting of the aneurysmally changed aorta, a basic theoretical model was worked out for explanation of "endotension". Also, there was designed and constructed in vitro an original experimental model using which the authors carried out a study into the relationship between the pressure in the aneurysm after its complete exclusion from the blood flow by an endovascular graft and the volume of the aneurysmal contents. Some factors described in the literature as influencing the pressure level in the aneurysm were at the given stage purposefully excluded. The volume of the "aneurysm" reproduced in our model was equal to 675 ml; each of five vascular grafts implanted into the aneurysm measured 110 mm in length. The pulsating liquid flow was reproduced in the system using a serial appliance for extracorporeal circulation. The liquid was aspirated from the aneurysm by means of a syringe with concurrent pressure guidance in the sac. To start pressure lowering, it was necessary to evacuate 0.4-1.6 ml of the liquid. The real clinical situations were considered from the standpoint of our results.

Aortic Aneurysm↗

Unstable carotid plaques exhibit raised matrix metalloproteinase-8 activity.

BACKGROUND: The fibrous cap of atherosclerotic plaques is composed predominantly of type I and III collagen. Unstable carotid plaques are characterized by rupture of their cap, leading to thromboembolism and stroke. The proteolytic mechanisms causing plaque disruption are undefined, but the collagenolytic matrix metalloproteinase (MMP) -1, -8, and -13 may be implicated. The aim of this study was to quantify the concentrations of these collagenases in carotid plaques and to determine their relationship to markers of plaque instability. METHODS AND RESULTS: Atherosclerotic plaques were collected from 159 patients undergoing carotid endarterectomy. The presence and timing of carotid territory symptoms were ascertained. Preoperative embolization was recorded by transcranial Doppler. Each plaque was assessed for histological features of instability. Plaque MMP concentrations were quantified with ELISA. Significantly higher concentrations of active MMP-8 were observed in the plaques of symptomatic patients (20.5 versus 11.4 ng/g; P=0.0002), in plaques of emboli-positive patients (22.7 versus 13.5 ng/g; P=0.0037), and in those plaques showing histological evidence of rupture (20.8 versus 14.7 ng/g; P=0.0036). No differences were seen in the levels of MMP-1 and MMP-13. Immunohistochemistry, in situ hybridization, and colocalization studies confirmed the presence of MMP-8 protein and mRNA within the plaque, which colocalized with macrophages. CONCLUSIONS: These data suggest that the active form of MMP-8 may be partly responsible for degradation of the collagen cap of atherosclerotic plaques. This enzyme represents an attractive target for drug therapy aimed at stabilizing vulnerable plaques.

Aged↗

An in vitro model to compare the antimicrobial activity of silver-coated versus rifampicin-soaked vascular grafts.

In situ replacement of infected vascular grafts is an accepted alternative to total graft excision and extraanatomic replacement. Its success relies upon the ability of the newly inserted graft to resist recurrent infection. This study compares the efficacy of two methods used to reduce the risk of graft reinfection: rifampicin soaking versus silver bonding of grafts. The grafts' resistance to infection was tested in vitro in two protocols, each using a panel of seven common bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The length of time the grafts remained free of organisms was compared between the groups. Both the silver graft and the rifampicin-soaked graft were significantly better than control graft at preventing bacterial growth on the graft surface. The rifampicin inhibited the growth of the gram-positive organisms, including MRSA, significantly better than the silver graft on days 2 and 3 (p < 0.001). Conversely, the silver graft was significantly more effective against the gram-negative organisms until day 4 (p < 0.0001). Both types of graft inhibit the in vitro growth of bacteria more effectively than controls, with rifampicin being most effective against gram-positive organisms and silver being best against the gram-negative organisms.

Acetates↗

The post-operative mortality of ruptured abdominal aortic aneurysm repair.

INTRODUCTION: Late peri-operative death after ruptured abdominal aortic aneurysm (RAAA) repair is usually due to multiple-organ failure. The aim of this study was to identify any factors that are associated with mortality in this group of patients. METHODS: A retrospective case-note review of a single decade's operative experience of RAAA repair in a single centre. Only those patients with confirmed rupture at laparotomy were included. Sixty-three pre- intra- and post-operative variables were recorded where possible for each patient who survived surgery and the initial 24-hours post-operatively. Multi-variate analysis was performed using stepwise logistic regression. The P-POSSUM, RAAA-POSSUM, RAAA-POSSUM (physiology only), V-POSSUM, and V-POSSUM (physiology only) models were all compared to determine how each performed in these patients. RESULTS: Two hundred and twenty-three cases of confirmed RAAA were identified, of whom 139 survived the operation and initial 24-hours post-operatively. In-hospital mortality in this group of patients was 32.4%. Variables significantly associated with mortality after multi-variate analysis, were low intra-operative systolic blood pressure, the presence of a consultant anaesthetist at the initial operation and the development of cardiac, renal or gastro-intestinal complications. All POSSUM models except the V-POSSUM and P-POSSUM (physiology only) models demonstrated no significant lack of fit in this dataset. DISCUSSION: Factors associated with delayed peri-operative death after RAAA are not the same as those previously found to be associated with overall peri-operative mortality after RAAA repair.

Aged↗

Does the sequence of clamp application during open abdominal aortic aneurysm surgery influence distal embolisation?

BACKGROUND: Embolisation of atherosclerotic debris during abdominal aortic aneurysm (AAA) repair is responsible for significant peri-operative morbidity. Reports have suggested that preferential clamping of the distal vessel(s) before the proximal aorta may decrease the number of emboli passing distally and hence reduce complications. METHODS: Forty patients undergoing AAA repair were randomised to have either first clamping of the proximal aorta or the iliac vessels. Emboli passing through the Superficial Femoral Arteries were detected with a Transcranial Doppler ultrasound system. RESULTS: There was no difference between the two groups in the number of emboli detected (p=0.49) and no significant correlation between number of emboli and dissection time (r=0.0008). However, there was a significantly higher number of emboli in the patient sub-group that were current smokers (p=0.034). CONCLUSIONS: There appears to be no difference in the numbers of emboli detected when the first vascular clamp is applied to the proximal aorta or iliacs.

Aged↗

The clinical value of the systemic inflammatory response syndrome (SIRS) in abdominal aortic aneurysm repair.

OBJECTIVES: The systemic inflammatory response syndrome (SIRS) is common after major surgery. We examine the dynamics of SIRS in AAA patients, and assess the impact of the number of SIRS criteria on patient outcome. DESIGN: Prospective study of 151 consecutive patients with AAA, undergoing repair electively, urgently or with rupture. METHODS: SIRS scores and organ failure scores were recorded prospectively each day for all patients. Outcome measures included length of stay, evidence of organ failure and mortality. RESULTS: The majority of patients developed SIRS postoperatively. Elective patients with a cumulative SIRS score of > or =10 during postoperative days 1-4 were more likely to die, compared to patients with a SIRS score of <10 (p=0.02). The development of SIRS late in the postoperative period (day 5-10) was associated with adverse outcome (death) in elective patients (p=0.01). The actual number of SIRS criteria present did not significantly correlate with either outcome or the incidence of organ failure. CONCLUSIONS: SIRS is common in patients undergoing AAA repair. The SIRS score provides useful information regarding a patient's physiological state. High SIRS scores, and the development of SIRS late in the postoperative period are associated with adverse outcome in elective patients, and can therefore be used as an indicator of potential problems.

Aged↗

Elevation in plasma MMP-9 following carotid endarterectomy is associated with particulate cerebral embolisation.

OBJECTIVES: To study plasma MMP-9 levels before and after carotid endarterectomy (CEA). DESIGN: Observational study. METHODS: Pre-operative (morning of surgery) and post-operative (48 h) plasma samples were obtained from 75 consecutive patients undergoing CEA. MMP-9 concentrations were quantified using ELISA. Transcranial Doppler monitoring was performed on each patient to detect particulate embolisation during the dissection phase of the CEA, until the application of carotid clamps. RESULTS: The median post-operative plasma MMP-9 level of emboli-positive patients was significantly higher than their median pre-operative value (14.9 ng/ml vs. 8.8 ng/ml; p=0.038). However, no significant difference was seen in the plasma MMP-9 level of emboli-negative patients (7.7 ng/ml vs. 7.1 ng/ml; p=0.364). A greater rise was seen in the median plasma MMP-9 levels of those patients suffering >2 emboli (from 3.4 to 19.3 ng/ml; p=0.041) than those patients suffering 1 or 2 emboli (from 10.1 to 12.8 ng/ml; p=0.340). CONCLUSIONS: Plasma MMP-9 only rises after CEA in patients with evidence of embolisation. This increase is more pronounced in those with high numbers of emboli. These data suggest that the increase in MMP-9 is due to cerebral damage caused by embolisation.

Aged↗

Cytokines, their genetic polymorphisms, and outcome after abdominal aortic aneurysm repair.

BACKGROUND: Excessive cytokine production has been implicated in the development of organ failure. Polymorphic sites in cytokine genes have been shown to affect levels of production in vitro and may influence cytokine production in vivo. The aims of this study were to determine if cytokines or their genetic polymorphisms were related to outcome after abdominal aortic aneurysm (AAA) repair. METHODS: A prospective study of 135 patients undergoing open AAA repair. Plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-10 were measured 24 h post-operatively and genotypes for the TNF-alpha -308, IL-1beta+3953, IL-6 -174, IL-10 -1082 and IL-10 -592 polymorphisms were determined for each patient. RESULTS: After elective AAA high levels of IL-10 were associated with both prolonged critical care (P<0.001) and hospital stay (P=0.001). The presence of a G allele at the IL-6 -174 locus was associated with a higher incidence of organ failure (P=0.04) and an A allele at TNF-alpha -308 with prolonged critical care stay (P=0.03). After ruptured AAA the development of multi-organ failure was associated with high levels of IL-6 (P=0.01) and TNF-alpha (P=0.04). High TNF-alpha levels were also associated with mortality (P=0.01). CONCLUSION: Post-operative cytokine levels are related to outcome after AAA repair. Cytokine gene polymorphisms may provide a method for determining which patients are at high risk of complications.

Aged↗

Feasibility of preoperative computer tomography in patients with ruptured abdominal aortic aneurysm: a time-to-death study in patients without operation.

INTRODUCTION: Despite advances in surgery, anaesthesia, and critical care, mortality from ruptured abdominal aortic aneurysms (AAAs) has not decreased over the last 20 years. Endovascular aneurysm repair (EVAR) of ruptured AAAs is an alternative to open repair, which may improve outcome. However, a computed tomography (CT) scan is usually required to assess the anatomic suitability of the aneurysm for EVAR. This may result in delay in transferring patients to the operating room. We evaluated all patients admitted to hospital with a ruptured AAA who died without undergoing surgery, to determine time to death after AAA rupture and thus the potential time available for obtaining a CT scan. METHODS: A retrospective case note review was conducted of 56 patients admitted to a single center with ruptured AAAs who did not undergo surgery because of advanced age or associated comorbidity over 8 years from 1995 to 2003. Statistical analysis was performed with the Fisher exact test. RESULTS: The 56 patients (33 men, 59%; 23 women, 41%) had a median age of 85 years (range, 71-98 years). Reasons for no operation being performed were shock (9%), cardiac arrest (11%), quality of life (29%), malignancy (7%), cardiac disease (15%), respiratory disease (16%) and age (14%). Median systolic blood pressure at admission was 110 mm Hg, heart rate was 88 beats per minute, and hemoglobin concentration was 10.5 g/dL. Patients were not aggressively resuscitated once a decision was made to not perform surgery. Death within 2 hours of hospital admission occurred in 7 (12.5%) patients, and 49 (87.5%) patients died more than 2 hours after admission. Median interval between onset of symptoms and admission to hospital was 2 hours 30 minutes (range, 44 minutes-36 hours), and the median interval between admission and death was 10 hours 45 minutes (range, 1 hour 1 minute-143 hours 55 minutes). The median total time to death from onset of symptoms was 16 hours 38 minutes (range, 2 hours 6 minutes-146 hours 50 minutes). CONCLUSION: Most (87.5%) patients admitted to hospital with a ruptured AAA died after more than 2 hours. These data show that most patients with a ruptured AAA who reach the hospital alive are sufficiently stable to undergo CT and consideration of EVAR.

Aged↗