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Biomedical subjects

P R Bell

Publications and source records attributed to P R Bell.

At least 19 recordsLinked to original sources

Factors affecting patency of subintimal infrainguinal angioplasty in patients with critical lower limb ischemia.

BACKGROUND: 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). METHODS AND RESULTS: 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). CONCLUSIONS: 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.

Adult↗

Evaluation by respirometry of the degradability of retort water using a shale ash and overburden packed column.

Oil shale processing produces an aqueous wastewater stream known as retort water. The fate of the organic content of retort water from the Stuart oil shale project (Gladstone, Queensland) is examined in a proposed packed bed treatment system consisting of a 1:1 mixture of residual shale from the retorting process and mining overburden. The retort water had a neutral pH and an average unfiltered TOC of 2,900 mg 1(-1). The inorganic composition of the retort water was dominated by NH4+. Only 40% of the total organic carbon (TOC) in the retort water was identifiable, and this was dominated by carboxylic acids. In addition to monitoring influent and effluent TOC concentrations, CO2 evolution was monitored on line by continuous measurements of headspace concentrations and air flow rates. The column was run for 64 days before it blocked and was dismantled for analysis. Over 98% of the TOC was removed from the retort water. Respirometry measurements were confounded by CO2 production from inorganic sources. Based on predictions with the chemical equilibrium package PHREEQE, approximately 15% of the total CO2 production arose from the reaction of NH4+ with carbonates. The balance of the CO2 production accounted for at least 80% of the carbon removed from the retort water. Direct measurements of solid organic carbon showed that approximately 20% of the influent carbon was held-up in the top 20cm of the column. Less than 20% of this held-up carbon was present as either biomass or as adsorbed species. Therefore, the column was ultimately blocked by either extracellular polymeric substances or by a sludge that had precipitated out of the retort water.

Biodegradation, Environmental↗

Growth, N2 fixation and photosynthesis in a cyanobacterium, Trichodesmium sp., under Fe stress.

Trichodesmium sp., isolated from the Great Barrier Reef lagoon, was cultured in artificial seawater media containing a range of Fe concentration. Fe additions stimulated growth, N2 fixation, cellular chlorophyll a content, light-saturated chlorophyll a-specific gross photosynthetic capacity (Pmchl a) and the dark respiration rate (Rdchl a). Cell yields only doubled for 9 nM Fe relative to zero added Fe, whereas N2 fixation increased 11-fold considerably for 450 nM Fe. The results suggest that N2 fixation of Trichodesmium is more sensitive to Fe limitation than are the cell yields.

Cells, Cultured↗

The physiological effects of elevated intra-abdominal pressure following aneurysm repair.

OBJECTIVES: 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. DESIGN: Prospective observational study. SETTING: University Hospital. SUBJECTS: 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. 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 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). CONCLUSIONS: 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.

Abdomen↗

A systematic review of outcome following synchronous carotid endarterectomy and coronary artery bypass: influence of surgical and patient variables.

OBJECTIVES: Outcomes after synchronous carotid endarterectomy (CEA) plus coronary artery bypass (CABG) relative to surgical and patient based variables. DESIGN: Systematic review of 94 published series (7863 synchronous procedures). RESULTS: 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'. CONCLUSIONS: Synchronous CEA + CABG is associated with a not insignificant cardiovascular risk. No comparable information is available for similar patients undergoing CABG without prophylactic CEA.

Carotid Stenosis↗

Enhanced invasive properties exhibited by smooth muscle cells are associated with elevated production of MMP-2 in patients with aortic aneurysms.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Aortic Aneurysm, Abdominal↗

Ubiquitous elevation of matrix metalloproteinase-2 expression in the vasculature of patients with abdominal aneurysms.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Aged↗

Plasma MMP-9 - a marker of carotid plaque instability.

OBJECTIVES: to investigate whether peripheral blood levels of matrix metalloproteinases (MMPs) or their inhibitors are altered in patients with particulate cerebral embolisation. DESIGN: a prospective study. MATERIALS AND METHODS: using sandwich enzyme immunoassay, plasma levels of MMPs-1, -2, -3 and -9, plus TIMPs-1 and -2 were quantified in 70 consecutive patients undergoing carotid endarterectomy. Patients were monitored with transcranial Doppler (TCD) preoperatively and during the dissection phase of the operation to detect those with spontaneous particulate embolisation (n =21). RESULTS: the plasma level of MMP-9 was significantly higher in those patients with evidence of spontaneous embolisation compared to those without. There were no differences in other MMP levels, or plasma concentrations of TIMPs. CONCLUSIONS: plasma MMP-9 levels are elevated in patients with particulate cerebral embolisation, and this may represent a novel marker of atherosclerotic plaque instability.

Aged↗

The impact of MRSA on vascular surgery.

OBJECTIVES: To investigate the prevalence of MRSA infection in patients treated in a major vascular unit and examine its consequences. DESIGN AND METHODS: A retrospective case-note review was performed. RESULTS: 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. CONCLUSION: 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.

Female↗

Cytokines and inflammatory pathways in the pathogenesis of multiple organ failure following abdominal aortic aneurysm repair.

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.

Aortic Aneurysm, Abdominal↗

Patients' thromboembolic potential between bilateral carotid endarterectomies remains stable over time.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Aspirin↗

Current status of carotid bifurcation angioplasty and stenting based on a consensus of opinion leaders.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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.

Angioplasty↗

Randomized trial of vein versus Dacron patching during carotid endarterectomy: influence of patch type on postoperative embolization.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Aged↗

Simple and reliable method of doxycycline determination in human plasma and biological tissues.

Over recent years there has been a resurgence in the use of doxycycline in clinical practice, which does not depend on its antibacterial properties. This paper describes a method of determination of doxycycline in human plasma and atheromatous tissue using high-performance liquid chromatography (HPLC), and a cheap commercially available extraction system. Doxycycline is extracted in the mobile phase and injected directly into the HPLC system, avoiding time consuming drying up steps. A limit of detection of 0.125 microg/ml of plasma, and a relative standard deviation of 3% was achieved, making the method very reliable and useful for assays within the usual therapeutic range. The method has also been applied to the extraction of a mixture of tetracyclines from plasma and atherma with equal efficacy, making it useful for assays of this class of drugs in veterinary practice and assays of food contaminants.

Anti-Bacterial Agents↗

Non-heart-beating organ donors: a potential source of islets for transplantation?

BACKGROUND: The shortage of organ donors relative to the number of patients on transplant waiting lists has led to a renewed interest in the use of non-heart-beating (NHB) organ donors in many centers. The lack of donors is also a problem for islet transplantation. The disparity between donor organs and potential recipients is further exacerbated by the requirement to transplant a large number of islets to increase the chance of success and the high level of variability in islet isolation yield. Non-heart-beating (NHB) donors have not previously been assessed as a source of islets for transplantation, and it is unknown what affects the additional factor of warm ischemic injury associated with NHB organs may have on the success of islet isolation. METHODS: This study assesses the yield and function of islets from NHB donors and compares the results with islets obtained from heart-beating brain-dead (HB) donors. RESULTS: There were no differences in the yield of islets per gram of pancreas, 1788 (0-4620) NHB vs. 1580 (26-2544) HB (median, range). The secretory function was also similar in both groups, with stimulation indices of 0.71-3.49 for NHB vs. 0.30-3.57 for HB (overall range). There was no correlation between islet yield and warm ischemia time in the NHB donor group. CONCLUSIONS: In conclusion, the study has demonstrated that it is possible to isolate large numbers of islets from NHB donor pancreata and that, where NHB donor programs exist, these could provide a significant addition to the number of potentially transplantable islets.

Adult↗