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Biomedical subjects

P L Harris

Publications and source records attributed to P L Harris.

At least 19 recordsLinked to original sources

The distaflo graft: a valid alternative to interposition vein?

INTRODUCTION: the rationale behind the Distaflo graft is inhibition of myointimal hyperplasia through optimisation of haemodynamic forces at the distal anastomosis. This prospective study reports our early clinical results. METHOD: patients with critical limb ischaemia, but no autologous vein, underwent infrainguinal bypass using Distaflo. Clinical and Duplex assessment provided prospective data from which one year cumulative patency, limb salvage and survival rates were calculated using Kaplan-Meier analysis. Log rank test enabled comparison with an historical control group of Miller cuff grafts. RESULTS: fifty Distaflo were inserted over 29 months into 46 patients, median age 68.5 years, 27 male (59%), of which 27 (54%) were re-do procedures. Proximal anastomoses were to common femoral arteries in 40 cases (80%); distal anastomoses were to popliteal vessels in 20 (40%), and tibial vessels in 30 (60%). The Distaflo graft had patency, limb salvage and survival rates of 39, 50 and 82% respectively compared to 49, 56 and 85% respectively in the control group, with no statistical difference (p = 0.39; 0.65; 0.67 respectively; log rank). CONCLUSION: in this non-randomised study, the Distaflo has similar one year patency, limb salvage and survival rates to the Miller cuff, potentially justifying its use an alternative in distal prosthetic arterial reconstruction for critical limb ischaemia.

Adult↗

Aortic side branch perfusion alone does not account for high intra-sac pressure after endovascular repair (EVAR) in the absence of graft-related endoleak.

OBJECTIVE: to examine the effect of stent-graft deployment on pressure within an aneurysm sac and to investigate the potential sources of intra-sac pressure. MATERIAL AND METHODS: intra-sac pressure was monitored during and immediately after endovascular repair via an indwelling catheter. Intra-sac pressure was also monitored during conventional open repair and was compared with the pressure measured within patent lumbar and inferior mesenteric side-branches, both before and after restoration of iliac arterial blood flow. Intra-sac and side-branch pressures were recorded and expressed as ratios of simultaneously measured radial artery pressure. RESULTS: in the absence of a graft-related endoleak (23/25 patients), endovascular repair resulted in a significant reduction in intra-sac pulse pressure (median ratio 0.31 IQR 0.10-0.46). There was no corresponding reduction in mean intra-sac pressure (median ratio 0.91; IQR 0.83-1.00). Application of clamps at conventional open repair resulted in a fall in both intra-sac pressure (median ratio 0.39, IQR 0.32-0.64) and pressure within side-branches (median ratio 0.45, IQR 0.33-0.64). Restoration of iliac blood flow resulted in a modest recovery of the side-branch pressure (median ratio 0.63, IQR 0.57-0.81), which nonetheless remained significantly less than the intra-sac pressure recorded after EVAR (p=0.01). CONCLUSION: reperfusion of the aneurysm sac through patent side-branches seems insufficient to account for persistent pressurisation of the aneurysm after endovascular repair. This finding supports the hypothesis that pressure may be transmitted directly through stent-graft fabric.

Aortic Aneurysm↗

The role of gadolinium-enhanced MR imaging in the preoperative evaluation of inflammatory abdominal aortic aneurysm.

Inflammatory abdominal aortic aneurysm is an uncommon variant of abdominal aortic aneurysms. Thorough preoperative imaging of the extent of the aneurysm and inflammation and the associated complications are crucial in the management of this condition. We report a case of inflammatory abdominal aortic aneurysm where, after the initial contrast-enhanced CT, gadolinium-enhanced MR imaging was used to define the true extent of the inflammation and differentiate inflammation from mural thrombus at the iliac extension of the aneurysm. The imaging appearances are presented and the impact of MR imaging on further surgical management options including endovascular repair are discussed.

Aortic Aneurysm, Abdominal↗

[Endovascular therapy of aneurysms of the abdominal aorta: report of 4,291 patients of the Eurostar Register].

BACKGROUND: The Eurostar project is a multicentred database of the outcome of endovascular repair of infra-renal aortic aneurysms. From 1996 to March, 2002, 113 European centres of vascular surgery have contributed. The purpose of this article is to review the medium term (up to 7 years) results of endovascular aneurysm repair as reported to Eurostar. PATIENTS AND METHODS: Patients intended for endovascular aneurysm repair were notified to the Eurostar Data Registry Centre before treatment in order to eliminate bias due to selective reporting. The following data was collected on all patients: (1) their demographic details and the anatomical characteristics of their aneurysms, (2) details of the endovascular device used, (3) procedural complications and the immediate outcome, (4) results of contrast enhanced CT imaging at 1, 3, 6, 12, 18 and 24 months after operation and at yearly intervals thereafter, (5) all adverse events. Life table analysis was performed to determine the cumulative rates of: (1) death from all causes, (2) secondary intervention. RESULTS: By March 2002, pre- and postoperative data of 4291 patients had been registered. The median duration of follow-up was 12 mo (range 0-96). Successful deployment was achieved in 97.8% of the patients with a perioperative (30 day) mortality of 2.4%. Early conversion to open repair occurred in 1.3%. Late rupture of the aneurysm occurred in 35 patients. The significant factors were endoleaks, graft migration and kinking. Late conversion to open repair occurred at an annual rate of approximately 2%. Risk factors (indications) for late conversion were endoleaks, graft migration and kinking. CONCLUSIONS: Endovascular repair of infra-renal aortic aneurysms using the first and second-generation devices that predominated in this study is associated with a risk of early or late failure of 3% per year, based upon an analysis of observed primary endpoints of rupture and conversion.

Adult↗

The influence of team experience on outcomes of endovascular stenting of abdominal aortic aneurysms.

OBJECTIVE: To determine whether the experience of the specialist team was associated with adverse events following endovascular treatment of abdominal aortic aneurysms. METHODS: The EUROSTAR database is a voluntary registry of 2863 patients admitted to 93 hospitals in Europe with an abdominal aortic aneurysm treated with endovascular stenting. Mortality, rupture and the need for secondary interventions were the main outcomes. RESULTS: In patients who underwent endovascular stenting by the most experienced specialist teams the mortality rate was 40% lower than in those treated by the least experienced teams (adjusted hazard ratio 0.60, 95% confidence interval: 0.4-1.0; p = 0.05). Also patients treated by the most experienced specialist teams were 68% less likely to have adverse events necessitating a secondary intervention than those treated by the least experienced teams (adjusted hazard ratio 0.32, 95% confidence interval: 0.2-0.5; p < 0.001). The crude rupture rate was 0.1% among patients treated by the most experienced specialist teams and 0.8% among those treated by the least experienced teams (p = 0.74). CONCLUSIONS: Specialist teams with a high level of experience of endovascular abdominal aortic aneurysm stenting encounter lower mortality rates and fewer adverse events leading to secondary interventions.

Adult↗

Experimental evaluation of flow patterns in interposition vein cuff anastomosis. The influence of non-planarity of the inflow.

Clinical evidence suggests that the development of myointimal hyperplasia in prosthetic femorodistal bypass grafts may be reduced by the interposition of a cuff of autologous vein between the graft and the recipient artery. Previous experimental work has shown that some of the benefits may be attributed to the geometry of the cuffed anastomosis. Since the distal anastomosis in vivo is often non-planar we have carried out a preliminary study in a model where the graft is at an angle of 45 degrees to the anterior-posterior plane of the anastomosis. This out-of-plane angulation produces highly asymmetric flow patterns in the anastomosis with significant flow separation on the ipsilateral side of the cuff. In the proximal and distal outflow, however, the velocity vectors show significant helical motion with temporal instability in the distal outflow.

Anastomosis, Surgical↗

Active glycation in neurofibrillary pathology of Alzheimer disease: N(epsilon)-(carboxymethyl) lysine and hexitol-lysine.

Advanced glycation end products are a diverse class of posttranslational modifications, stemming from reactive aldehyde reactions, that have been implicated in the pathogenesis of a number of degenerative diseases. Because advanced glycation end products are accelerated by, and result in formation of, oxygen-derived free radicals, they represent an important component of the oxidative stress hypothesis of Alzheimer disease (AD). In this study, we used in situ techniques to assess N(epsilon)-(Carboxymethyl)lysine (CML), the predominant advanced glycation end product that accumulates in vivo, along with its glycation-specific precursor hexitol-lysine, in patients with AD as well as in young and aged-matched control cases. Both CML and hexitol-lysine were increased in neurons, especially those containing intracellular neurofibrillary pathology in cases of AD. The increase in hexitol-lysine and CML in AD suggests that glycation is an early event in disease pathogenesis. In addition, because CML can result from either lipid peroxidation or advanced glycation, while hexitol-lysine is solely a product of glycation, this study, together with studies demonstrating the presence of 4-hydroxy-2-nonenal adducts and pentosidine, provides evidence of two distinct oxidative processes acting in concert in AD neuropathology. Our findings support the notion that aldehyde-mediated modifications, together with oxyradical-mediated modifications, are critical pathogenic factors in AD.

Adult↗

Melatonin acts as antioxidant and pro-oxidant in an organotypic slice culture model of Alzheimer's disease.

An organotypic mouse brain slice culture system of Alzheimer's disease (AD) under low oxygen partial pressures was developed to determine the antioxidant properties of the pineal hormone melatonin in vitro. Assays for biochemical markers of oxidative stress including redox active iron assay, heme-oxygenase-1 and 8-hydroxyguanosine inmunoreactivity were performed along with morphological analysis for stressed tissue following amyloid-beta (A beta) 1-40 insult. Melatonin (100 microM) significantly reduced the appearance of condensed chromatin, redox active iron, heme-oxygenase-1 induction and 8-hydroxyguanosine immunoreactivity caused by 50 microM A beta. Melatonin also prevented A beta-induced morphological signs of oxidative stress in tissue ultrastructure, including edema and dark degenerating profiles as visualized under electron microscope. At elevated concentrations (1 mM), melatonin induced redox active iron and heme-oxgenase-1 immunoreactivity. Thus, while melatonin may be a potential therapeutic agent in the prevention of oxidative stress associated with A beta and AD, it can also induce markers of oxidative stress at millimolar concentrations.

Alzheimer Disease↗

Mitochondrial abnormalities in Alzheimer's disease.

The finding that oxidative damage, including that to nucleic acids, in Alzheimer's disease is primarily limited to the cytoplasm of susceptible neuronal populations suggests that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress of Alzheimer's disease. In this study, we used in situ hybridization to mitochondrial DNA (mtDNA), immunocytochemistry of cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens to determine whether there are mitochondrial abnormalities in Alzheimer's disease and their relationship to oxidative damage marked by 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons showing increased oxidative damage in Alzheimer's disease have a striking and significant increase in mtDNA and cytochrome oxidase. Surprisingly, much of the mtDNA and cytochrome oxidase is found in the neuronal cytoplasm and in the case of mtDNA, the vacuoles associated with lipofuscin. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship shown here between the site and extent of mitochondrial abnormalities and oxidative damage suggests an intimate and early association between these features in Alzheimer's disease.

Adolescent↗

Lessons learnt from the EUROSTAR registry on endovascular repair of abdominal aortic aneurysm repair.

OBJECTIVE: The EUROSTAR project is a multicentred database of the outcome of endovascular repair of infra-renal aortic aneurysms. To date 92 European centres of vascular surgery have contributed. The purpose of the article here is to review the medium term (up to 4 years) results of endovascular aneurysm repair as reported to Eurostar. PATIENTS AND METHODS: Patients intended for endovascular aneurysm repair were notified to the EUROSTAR Data Registry Centre before treatment in order to eliminate bias due to selective reporting. The following data was collected on all patients: (1) their demographic details and the anatomical characteristics of their aneurysms, (2) details of the endovascular device used, (3) procedural complications and the immediate outcome, (4) results of contrast enhanced CT imaging at 3, 6, 12 and 18 months after operation and at yearly intervals thereafter, (5) all adverse events. Life table analysis was performed to determine the cumulative rates of: (1) death from all causes, (2) secondary intervention. Risk factors for rupture and late conversion were identified by regression analysis. RESULTS: By July 2000, 2862 patients had been registered and their median duration of follow-up was 12 mo (range 0-72). Successful deployment was achieved in 2812 patients with a perioperative (30 day) mortality of 2.9%. In 2464 patients enrolled by March 2000 late rupture of the aneurysm occurred in 14 patients for an annual cumulative rate of 1%. The significant factors were proximal type I endoleak (P=0.001), midgraft (type III) endoleak (P=0.001), graft migration (P=0.001) and post-operative kinking of the endograft (P=0.001). Forty-one patients had late conversion to open repair for an annual cumulative rate (risk) of approximately 2.1%. Risk factors (indications) for late conversion were: proximal type I endoleak (P=0.001), midgraft (type III) endoleak (P=0.001), type II endoleak (P=0.003), graft migration (P=0.001), graft kinking (P=0.001) and distal type I endoleak (P=0.001). CONCLUSIONS: Endovascular repair of infra-renal aortic aneurysms using the first and second-generation devices that predominated in this study was associated with a risk of late failure of 3% per year, based upon an analysis of observed primary endpoints of rupture and conversion. Eurostar continues to provide responsible evaluation of the technique for the benefit of both physicians and the industry.

Adult↗

Aortic side branch embolization before endovascular aneurysm repair: incidence of type II endoleak.

PURPOSE: To assess the feasibility of embolization of aortic side branches and its impact on the incidence of type II endoleak after endovascular aneurysm repair. MATERIALS AND METHODS: Endovascular aneurysm repair was performed in 74 patients. Aortic side branch vessels were evaluated on the preoperative angiogram and computed tomography (CT) and, where embolization of lumbar and inferior mesenteric vessels was considered technically possible, this was attempted prior to endovascular repair. Follow-up CT was used to assess the presence of type II endoleak. RESULTS: Seventy-two patients were followed up for longer than 1 month. Embolization was attempted in 25 cases, successfully in 10, with partial success in 11, and failure in four. Twenty patients with successful or partly successful preoperative embolization were discharged and followed-up. Four (20%) had demonstrable type II endoleak during follow-up, with two of these persisting at latest follow-up. Of 43 patients without previous embolization, there were 10 (23.3%) type II endoleaks during the follow-up period, four of these persisting. In cases with type II endoleak, mean sac diameter change was -0.5 mm in the cases with previous embolization and +3.1 mm without. The mean period to onset of type II endoleak was 6.9 months without, and 15.3 months with, previous embolization. CONCLUSION: Although the cohort size is below a level that would confer significance, the trend of these findings is such as to suggest a lack of influence of aortic side branch embolization on the incidence of type II endoleak during the follow-up period.

Angiography↗

Optimising miller cuff dimensions: the influence of geometry on anastomotic flow patterns.

OBJECTIVES: since cuff dimensions are variable, we studied the influence of cuff geometry on flow mechanics, in an attempt to identify the optimum configuration. MATERIALS AND METHODS: bench studies involved the manufacture of anatomically accurate models of varying cuff dimensions, perfused in a specifically designed flow rig, simulating physiological conditions. Flow visualisation studies incorporating laser illumination of tracer particles enabled accurate analysis of flow patterns. RESULTS: the vortex created within the proximal cuff of each model during the deceleration phase of the cardiac cycle was strongly influenced by the aspect ratio (AR=cuff height:length). The standard and high cuffs (AR=1.63 and 1.18, respectively) demonstrated cohesive vortices and stable flow patterns. Low and long cuffs (AR=2.6 and 2.25, respectively) created more complex vortices with large areas of flow separation and low velocities. CONCLUSIONS: aspect ratio has an important influence on flow within the distal anastomosis, with cuff dimensions of 13 mm long and 8-11 mm high (standard and high cuffs) creating beneficial flow patterns anticipated to optimise wall shear stress and inhibit myointimal hyperplasia.

Anastomosis, Surgical↗

Risk factors for endoleak and the evidence for stent-graft oversizing in patients undergoing endovascular aneurysm repair.

OBJECTIVES: the aim of this study was to assess the relationship between patient factors, the anatomy of the proximal aneurysm neck; the type of endovascular graft; and the consequences of graft/neck size mismatch and the occurrence of proximal endoleak. Design multicentre clinical study. MATERIALS: of a total of 2194 patients, 2146 underwent successful endovascular repair of infra-renal abdominal aortic aneurysms (AAA). METHODS: endoleaks were identified by radiological imaging immediately after completion of the procedure as per study protocols. Clinical and anatomical features of AAA in patients with endoleak were compared to patients without endoleak and data were analysed using the Chi-square test. A multivariate logistic regression model was constructed by selecting variables found to be significantly associated with complications in a univariate analysis. RESULTS: intra-operative endoleak was observed in 16.7% overall, and 3.3% were noted to have proximal endoleak. Aneurysm size larger than 60 mm (p =0.004), ex-smokers ( p =0.005) and age over 75 years ( p =0.01) were independently associated with endoleak of all types. Univariate and multivariate analysis revealed correlation between proximal endoleak and (i) diameter of the aneurysm neck-proximal (D2a), middle (D2b), distal (D2c), at all levels (p <0.005); (ii) proximal aortic neck length ( p =0.0001); (iii) aortic device diameter ( p =0.0024). No correlation was identified for angulation and form of the aortic neck. A model of the frequency of proximal endoleak, in relation to the ratio of the aortic device diameter to the distal aortic neck diameter, revealed that endoleak decreased when the aortic device diameter became oversized by more than 10% and confidence intervals remained tight for up to and over 20% oversize.

Adult↗

Harnessing haemodynamic forces for the suppression of anastomotic intimal hyperplasia: the rationale for precuffed grafts.

OBJECTIVES: Standardisation of cuff geometry by manufacturing prosthetic precuffed grafts (PCG) theoretically optimises haemodynamic forces. This study was designed in order to determine whether these beneficial flow patterns are replicated in vivo in PCG. PATIENTS AND METHODS: Flow visualisation and Doppler studies performed on anatomically accurate PCG models characterised in vitro anastomotic flow patterns. Thirty-two patients (median age 68 years) in whom autologous vein was unavailable, underwent bypass using PCG. Post-operative analysis included qualitative assessment of flow within the distal anastomosis using Doppler colour flow mapping. Cardiac gating techniques and assessment of velocity distribution were performed to gain additional information. These in vivo results were validated against the bench studies. RESULTS: A cohesive vortex was identified within the distal anastomosis of in vitro models and had an integral relationship with the cardiac cycle. This flow structure was also characterised using Doppler colour flow mapping in both longitudinal and transverse planes, confirming the location of the vortex within the body and proximal part of the anastomosis. Twenty-two patients (69%) undergoing bypass with a PCG underwent successful Doppler assessment one week post-operatively, of whom 17 (77%) had a vortical flow structure identified at the distal anastomosis, similar to that characterised in vitro. Cardiac gating verified the same integral relationship of the vortex with the cardiac cycle as that described in vitro. CONCLUSION: The geometric configuration of precuffed grafts induced vortices within the distal anastomoses in 17 out of 22 patients undergoing arterial reconstruction, thereby harnessing the haemodynamic forces that may suppress anastomotic hyperplasia and improve patency rates.

Adult↗

Perianeurysmal fibrosis: a relative contra-indication to endovascular repair.

OBJECTIVE: Perianeurysmal fibrosis (PAF) with involvement of neighbouring viscera can render open repair of inflammatory aneurysms technically difficult and therefore hazardous. For this reason, endovascular repair (EVAR) has been advocated as the preferred approach for this condition. EVAR is known to induce a systemic inflammatory response in patients but the nature of the local response remains unknown. If significant, such a response could exacerbate rather than ameliorate PAF. The aim of the study was to examine the incidence, course and consequences of perianeurysmal fibrosis detected by computerised tomography (CT) before and after EVAR. MATERIAL AND METHODS: The clinical records of patients treated by EVAR and followed for at least 6 months were reviewed. Pre and post-operative CT images were independently graded for PAF by three radiologists according to a standard protocol. RESULTS: PAF was documented preoperatively in six out of a total of 61 patients. In two of these PAF worsened after EVAR resulting in ureteric obstruction and hydronephrosis requiring ureteric stents. In the remaining 4 patients PAF did not reduce postoperatively. PAF of low grade developed postoperatively in 10 out of 55 patients (18%) in whom there was no evidence of PAF on preoperative imaging. Median follow-up was 18 months (range 6-36 months). The development of periaortic fibrosis de novopostoperatively was statistically significant (McNemar's test p=0.002). CONCLUSION: EVAR does not seem to reverse PAF if this is present preoperatively and it induces this condition in approximately one sixth of patients without evidence of preoperative PAF. The potential for this adverse inflammatory local response should be taken into account when considering EVAR for treatment of aneurysms with perianeurysmal fibrosis and must be weighed against the perceived benefits of this approach.

Aged↗

Mitochondrial function and oxygen supply in normal and in chronically ischemic muscle: a combined 31P magnetic resonance spectroscopy and near infrared spectroscopy study in vivo.

PURPOSE: We used (31)P magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) as a means of quantifying abnormalities in calf muscle oxygenation and adenosine triphosphate (ATP) turnover in peripheral vascular disease (PVD). METHODS: Eleven male patients with PVD (mean age, 65 years; range, 55-76 years) and nine male control subjects of similar age were observed in a case-control study in vascular outpatients. Inclusion criteria were more than 6 months' calf claudication (median, 1.5 years; range, 0.6-18 years); proven femoropopliteal or iliofemoral occlusive or stenotic disease; maximum treadmill walking distance (2 km/h, 10 degrees gradient) of 50 to 230 m (mean, 112 m); ankle-brachial pressure index of 0.8 or less during exercise (mean, 0.47; range, 0.29-0.60). Exclusion criteria included diabetes mellitus, anemia, and magnet contraindications. Simultaneous (31)P MRS and NIRS of lateral gastrocnemius was conducted during 2 to 4 minutes of voluntary 0.5 Hz isometric plantarflexion at 50% and 75% maximum voluntary contraction force (MVC), followed by 5 minutes recovery. Each subject was studied three times, and the results were combined. RESULTS: Compared with control subjects, patients with PVD showed (1) normal muscle cross-sectional area, MVC, ATP turnover, and contractile efficiency (ATP turnover per force/area); (2) larger phosphocreatine (PCr) changes during exercise (ie, increased shortfall of oxidative ATP synthesis) and slower PCr recovery (47% +/- 7% [mean +/- SEM] decrease in functional capacity for oxidative ATP synthesis, P = .001); (3) faster deoxygenation during exercise and slower postexercise reoxygenation (59% +/- 7% decrease in rate constant, P = .0009), despite reduced oxidative ATP synthesis; (4) correlation between PCr and NIRS recovery rate constants (P < .02); and (5) correlations between smaller walking distance, slower PCr recovery, and reduced MVC (P < .001). The precision of the key measurements (rate constants and contractile efficiency) was 12% to 18% interstudy and 30% to 40% intersubject. CONCLUSION: The primary lesion in oxygen supply dominates muscle metabolism. Reduced force-generation in patients who are affected more may protect muscle from metabolic stress.

Adenosine Triphosphate↗

Let's swap: early understanding of social exchange by British and Nepali children.

Recent research with adults has suggested that they readily understand conditional rules that include a deontic or prescriptive element. The possibility that young children might also understand such conditional rules when they are embedded in the context of an exchange agreement was explored in three studies. Children 3-7 years of age listened to stories in which two protagonists agreed to an exchange of mutual benefit. Children tested both in Britain and Nepal were accurate in identifying (1) when either protagonist had reneged on the agreement and (2) when both protagonists had kept the agreement. The findings indicate that young children are sensitive to the obligations that stem from an exchange agreement even if it is made between equals rather than imposed by adult authority.

Child↗