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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
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Methylene blue based protein solder for vascular anastomoses: an in vitro burst pressure study.

BACKGROUND AND OBJECTIVE: Attempts at sutureless anastomoses have used protein-based solders containing chromophores [Oz et al., J Vasc Surg 1990;11:718; Poppas et al., J Urol 1998150:1052] to enhance the strength of laser anastomoses. Reports have described the use of indocyanine green [Oz et al., Surg Forum 1989;316.], fuschin, and fluorescein isothiocyanate as chromophores [Chuck et al. , Lasers Surg Med 1989;9:471; Vance et al., Lasers Med Sci 1988;3:219]. Methylene blue (MB) is a chromophore with absorption peaks in the 600-700 nm region whose use has not been reported in laser-assisted vascular anastomoses. Therefore, we set out to produce and characterise a MB-containing protein solder. The absorption and burst pressure characteristics have been investigated and described as well as a brief review of the chemical and biological properties of MB. STUDY DESIGN/MATERIALS AND METHODS: The MB and porcine serum albumin (PSA)-based solder was produced and used to form end-to-end anastomoses in porcine splenic arteries. The solder was activated using a laser diode emitting at 670 nm. The burst pressures of the anastomoses were tested, and the results analysed as a function of MB concentration and absorption. In addition, the relationship between MB concentration and absorption was examined. RESULTS: A dose-response relationship was found between the measured absorption of the solder and the burst pressure of the anastomoses formed. Burst pressures exceeding physiological levels were found. Changes in MB concentration revealed a marked negative deviation from Beer's law at 670 nm, owing to the monomer-dimer-trimer equilibria. CONCLUSION: PSA with MB solder is able to form high-quality end-to-end anastomoses, with immediate burst pressure profiles similar to those previously described for sutured [Quigley et al., Microsurgery 1985;6:229], lasered [Quigley et al., Microsurgery 1985;6:229], and soldered anastomoses [Small et al., J Clin Laser Med Surg 1997;15:205]. The relationship between burst pressure strength and chromophore absorption is discussed.

Absorption↗
PubMed2000

Estimating normal and pathological dynamic responses in cerebral blood flow velocity to step changes in end-tidal pCO2.

The regulation of cerebral blood flow (CBF) following changes in arterial blood pressure (ABP) and end-tidal pCO2 (EtCO2) are of clinical interest in assessing cerebrovascular reserve capacity. Linear finite-impulse-response modelling is applied to ABP, EtCO2 and CBF velocity (CBFV, from transcranial Doppler measurements), which allows the CBFV response to ideal step changes in EtCO2 to be estimated from clinical data showing more sluggish, and additional random variations. The confounding effects of ABP changes provoked by hypercapnia on the CBFV are also corrected for. Data from 56 patients suffering from stenosis of the carotid arteries (with normal or diminished cerebrovascular reactivity to EtCO2 changes--CVRCO2) were analysed. The results show the expected significant differences (p < 0.05) between EtCO2 steps up and down, the significant contribution from ABP variation, and also differences in the dynamic responses of patients with reduced CVRCO2 (p < 0.01 after 10 s). For the latter the CBFV response appears exhausted after about 15 s, whereas for normals CBFV continues to increase. While dispersion of individual step responses remains large, the method gives encouraging results for the non-invasive study of compromised haemodynamics in different patient groups.

Aged↗
PubMed2000

Comparison of cognitive function and quality of life after endovascular or conventional aortic aneurysm repair.

INTRODUCTION: The long-term effects of endovascular aortic aneurysm repair on cognitive function and quality of life are not known. METHODS: The cognitive function and quality of life of 82 patients undergoing aortic aneurysm repair (34 endovascular and 48 conventional procedures) were assessed before and 6 months after operation. Cognitive function was quantified using a battery of psychometric tests. Quality of life was assessed with the Medical Outcomes Short Form 36 (SF-36) questionnaire. RESULTS: Data at 6 months were available for 78 per cent of patients. As a group the patients showed a significant decline on one cognitive function test (visual search) and on two domains of the SF-36 (physical function and vitality) when they were reassessed. There were no significant differences between patients undergoing endovascular or conventional aneurysm repair after 6 months in cognitive function or quality of life. CONCLUSION: Endovascular aneurysm surgery had a similar impact on health-related quality of life and cognitive function compared with conventional aneurysm repair. Patients in both groups demonstrated a significant decline in cognitive function.

Aged↗
PubMed2000

Localization of matrix metalloproteinase 2 within the aneurysmal and normal aortic wall.

BACKGROUND: Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2-MT1-MMP-tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue. METHODS: Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography. RESULTS: All components of the MMP-2-TIMP-2-MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta. CONCLUSION: The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2-TIMP-2-MT1-MMP enzyme system to the medial layer of the arterial wall gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs.

Aged↗
PubMed2000

Pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury.

OBJECTIVES: to investigate endogenous pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury. METHODS: groups of male Wistar rats (n=6) were subjected to 60 minutes of infrarenal aortic cross-clamping under general anaesthesia. Rats were culled after 0, 60 and 120 minutes>> reperfusion, following release of the aortic clamp. A sham-operated control group was also studied. Acute lung injury (ALI) was quantified by measuring the protein concentration in lung bronchoalveolar lavage (BAL) fluid. Pulmonary myeloperoxidase activity (MPO) was measured as an index of neutrophil infiltration and degranulation in the lung. Plasma tumour-necrosis factor-alpha (TNF-alpha) was measured as an index of the pro-inflammatory cytokine response and pulmonary nitric oxide synthase (NOS) activity was determined by measuring conversion of(3)H L-arginine to(3)H L-citrulline in tissue homogenates. RESULTS: these data show significant ALI with increased pulmonary microvascular permeability and MPO activity in animals subject to 60 minutes>> ischaemia and 60 minutes or 120 minutes of reperfusion compared to control animals (p<0.01). Plasma TNF-alpha levels were significantly increased following 60 minutes of ischaemia compared to controls (p<0.01) and remained significantly increased in animals subject to reperfusion (p<0.01). Pulmonary NOS activity was significantly increased in animals subject to reperfusion (p<0.01). CONCLUSIONS: the reperfusion phase of infrarenal aortic cross-clamping provokes a significant increase in pulmonary NOS metabolism. The increase in plasma TNF-alpha and MPO activity suggests that this response may be secondary to inducible NOS expression. Manipulation of this response may benefit patients at risk of acute injury following infrarenal aortic reconstruction.

Animals↗
PubMed2000

Transcranial Doppler-directed Dextran-40 therapy is a cost-effective method of preventing carotid thrombosis after carotid endarterectomy.

OBJECTIVES: perioperative stroke reduces the clinical effectiveness of carotid endarterectomy (CEA). Postoperative thrombotic stroke may be reduced in incidence by the use of transcranial Doppler-directed Dextran-40 therapy. This programme requires the purchase of additional equipment and employment of more staff. This study examined whether this additional financial outlay was cost-effective in terms of saving expenditure by preventing postoperative thrombotic stroke. MATERIALS AND METHODS: data was collected prospectively on a series of 600 consecutive CEAs. The costs of the monitoring programme were analysed over 1- and 5-year periods. Formulae were derived allowing other units to calculate whether this technique will be cost-effective for them. RESULTS: after the introduction of TCD monitoring the postoperative thrombotic stroke rate fell from 2.7% to 0% (8 strokes prevented). Our local unit cost for the treatment of stroke was 25,702 pounds. After allowing for the additional costs of the monitoring programme, we calculate that postoperative TCD has saved 171,393 pounds. CONCLUSIONS: postoperative TCD monitoring is a clinically effective and also cost-effective method of reducing the stroke rate associated with CEA. For units performing more than 50 CEAs per year who experience occasional postoperative carotid thrombosis, its introduction should be considered.

Aged↗
PubMed2000

Prevention of renal impairment following aortic cross-clamping by manipulation of the endogenous renal nitric oxide response.

OBJECTIVE: Infrarenal aortic cross-clamp-induced lower torso ischaemia-reperfusion injury is associated with impairment of glomerular filtration rate and upregulation of endogenous renal nitric oxide production. The aim of this study was to investigate whether manipulation of the endogenous renal nitric oxide response can ameliorate subsequent renal injury. METHODS: Groups of male Wistar rats (n = 6) were treated with one of the following agents before being subjected to 60 min of infrarenal aortic cross-clamping: saline (control), L-NMMA (a pan nitric oxide synthase inhibitor), 1400W (a highly selective iNOS inhibitor), hydrocortisone (an inhibitor of the systemic inflammatory response), L-arginine (the substrate for nitric oxide synthase) and NOC-18 (a nitric oxide donor). Animals were recovered after a left nephrectomy. The glomerular filtration rate (GFR) of the remaining kidney was measured on the second and seventh postoperative day using a 99Tc DPTA clearance technique as an index of renal injury. RESULTS: Animals treated with L-NMMA prior to aortic cross-clamping had a significantly impaired GFR compared to controls on the second (p<0. 01, Mann-Whitney U -test) and seventh (p<0.05, Mann-Whitney U -test) postoperative day. Hydrocortisone and 1400W had no significant effect on GFR on the second or seventh postoperative day. L-arginine and NOC-18 had no influence on GFR on the second postoperative day but significantly improved GFR on the seventh postoperative day. CONCLUSIONS: These results show that the endogenous nitric oxide response protects the kidneys from ischaemia-reperfusion injury. Manipulation of the renal nitric oxide response may have therapeutic benefits to patients undergoing aortic aneurysm repair by preventing acute renal failure.

Animals↗
PubMed2000

The Pruitt-Inahara shunt maintains mean middle cerebral artery velocities within 10% of preoperative values during carotid endarterectomy.

OBJECTIVE: The purpose of this study was to assess the ability of the Pruitt-Inahara shunt to maintain adequate middle cerebral artery velocities during carotid endarterectomy. STUDY DESIGN: Prospectively collected data recorded during 548 carotid endarterectomies performed at a single university hospital were analyzed to look at changes in cerebral blood flow velocities at different stages during the procedure. Parallel data relating to blood pressure and end-tidal carbon dioxide were also examined. RESULTS: During the first carotid artery cross clamp, middle cerebral artery velocity fell by 42%. A total of 169 patients (31%) had velocities that fell below 15 cm/s (electrical activity in the brain becomes altered below this level). After shunt insertion, only 2% of patients had middle cerebral artery velocities less than 15 cm/s. In only one patient was the velocity less than 10 cm/s. Increased systolic or diastolic blood pressure raised flow through the shunt significantly (P =.001). When two criteria used for selective shunt use were compared, only a moderate correlation was found between absolute middle cerebral artery velocity after carotid cross clamping and percentage change in middle cerebral artery velocity relative to preclamp values. CONCLUSIONS: The Pruitt-Inahara shunt is able to maintain adequate middle cerebral artery velocity in 98% of patients undergoing carotid endarterectomy. Alterations in blood pressure can significantly affect flow through the shunt.

Blood Flow Velocity↗
PubMed2000

Reducing the risk of carotid surgery: a 7-year audit of the role of monitoring and quality control assessment.

BACKGROUND AND PURPOSE: The current risk of stroke after carotid endarterectomy may be worse than reported in the international trials. Because studies have suggested that most operative strokes follow surgeon error, the aim of the current study was to audit the impact of introducing a strategy of perioperative monitoring and quality control assessment on outcome. METHODS: A total of 500 patients underwent carotid endarterectomy with intraoperative transcranial Doppler scan monitoring, completion angioscopy, and 3 hours of postoperative transcranial Doppler scan monitoring. The last of these guided selective dextran therapy in patients with high rates of postoperative embolization, which in previous series has been shown to be highly predictive of progression to thromboembolic stroke. RESULTS: Intimal flaps were repaired in 3% of patients and luminal thrombus removed in 4% of patients. The rate of intraoperative stroke was 0.2%. A total of 313 patients had more than one embolus detected postoperatively (96% within 2 hours of flow restoration), but only 22 patients had sustained embolization requiring dextran. Embolization ceased in all but one patient receiving dextran, although the dose had to be increased in seven patients (36%). One patient was unable to receive adequate dextran therapy because of severe cardiac failure. Overall, the 30-day death/stroke rate was 2.2%, no patient had a perioperative stroke because of carotid thrombosis, and the rate of ipsilateral embolic stroke was 0.8%. Most complications resulted from cardiac pathology or intracranial hemorrhage. CONCLUSIONS: A program of monitoring and quality control assessment has been associated with a 60% decrease in the operative risk in comparison with that observed before implementation of the protocol.

Clinical Protocols↗
PubMed2000

Increased matrix metalloproteinase 2 expression in vascular smooth muscle cells cultured from abdominal aortic aneurysms.

OBJECTIVES: Recent evidence has implicated matrix metalloproteinase 2 (MMP-2) in the pathogenesis of aneurysms. The aim of this study was to examine MMP-2 production and expression by aortic smooth muscle cells (SMCs) and dermal fibroblasts derived from patients with abdominal aortic aneurysms (AAAs). METHODS: Aortic SMCs and dermal fibroblasts were cultured from patients with AAAs or from age-matched controls with atherosclerosis. The production of MMP and tissue inhibitor of metalloproteinase into culture media was analyzed with the use of gelatin zymography, Western blotting, and enzyme-linked immunosorbent assay. Gene expression was analyzed with Northern blotting. RESULTS: All cells studied constitutively produced MMP-2. Aortic SMCs cultured from aneurysmal tissue expressed MMP-2 protein and messenger RNA at a significantly higher level than SMCs from controls (P =.008). Dermal fibroblasts from patients with AAAs expressed MMP-2 at a similar level to controls. In both cell types, tissue inhibitor of metalloproteinase 2 and membrane type 1-MMP were expressed at similar levels. CONCLUSIONS: These data suggested that the regulation of MMP-2 gene expression was altered in the aortic SMCs of patients with aneurysms, but this finding was not repeated in other mesenchymal tissue.

Aged↗
PubMed2000

Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption.

BACKGROUND AND PURPOSE: Acute disruption of atherosclerotic plaques precedes the onset of clinical syndromes, and studies have implicated a role for matrix metalloproteinases (MMPs) in this process. The aim of this study was to establish the character, level, and expression of MMPs in carotid plaques and to correlate this with clinical status, cerebral embolization, and histology. METHODS: Plaques were obtained from 75 consecutive patients undergoing carotid endarterectomy and divided into 4 groups according to symptomatology (group 1, asymptomatic; group 2, symptomatic >6 months before surgery; group 3, symptomatic within 1 to 6 months; group 4, symptomatic within 1 month). All patients underwent preoperative and intraoperative transcranial Doppler monitoring. Plaques were subjected to histological examination and quantification of MMPs by zymography and ELISA. RESULTS: The level of MMP-9 was significantly higher in group 4 (median 125.7 ng/mL for group 4, median <32 ng/mL for all other groups; P=0.003), with no difference in the levels of MMPs 1, 2, or 3. Furthermore, the MMP-9 concentration was significantly higher in plaques undergoing spontaneous embolization (P=0.019) and those with histological evidence of plaque instability (P<0.03). In situ hybridization demonstrated increased MMP-9 expression in highly symptomatic plaques in areas of intense inflammatory infiltrate. CONCLUSIONS: The concentration, production, and expression of MMP-9 is significantly higher in unstable carotid plaques. If this proves to be a causal relationship, MMP-9 may be a strong candidate for pharmacotherapy aimed at stabilizing plaques and preventing stroke.

Aged↗
PubMed2000

Endovascular repair of an innominate artery false aneurysm following blunt trauma.

PURPOSE: To describe a case of endovascular graft exclusion of an innominate artery pseudoaneurysm arising from blunt trauma. METHODS AND RESULTS: A 21-year-old patient was admitted following a major road accident. Computed tomography (CT) and aortography on admission disclosed an isolated innominate artery pseudoaneurysm. The lesion was stable, so an elective endoluminal repair was undertaken once the patient was treated for his other injuries. The right carotid artery was exposed and controlled, and the aneurysm was excluded by transluminal implantation of a customized stent-graft consisting of predilated polytetrafluoroethylene graft material covering a balloon-expandable Palmaz stent. A CT scan at 1 month and duplex scans at 6-month intervals documented good stent-graft positioning and aneurysm exclusion over a period of 18 months. CONCLUSIONS: This case illustrates the potential durability of endoluminal repair of innominate artery lesions and highlights the potential role of this minimally invasive alternative to surgery in these clinical situations.

Accidents, Traffic↗