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Biomedical subjects

N J London

Publications and source records attributed to N J London.

At least 19 recordsLinked to original sources

Duplex ultrasound scanning is reliable in the detection of endoleak following endovascular aneurysm repair.

OBJECTIVE: To investigate the value of duplex ultrasound scanning (DUSS) in the routine follow up of patients following EVAR. METHODS: Imaging was reviewed for 310 consecutive patients undergoing EVAR at a single centre. Concurrent ultrasound and CT scans were defined as having occurred within 6 months of each other. There were 244 paired concurrent DUSS and CT scans which were used for further analysis. These modalities were compared with respect to sensitivity, specificity, positive and negative predictive values and level of agreement (by Kappa statistics) using CT as the 'gold standard'. RESULTS: DUSS failed to detect a number of endoleaks which were seen on CT and the sensitivity of this test was therefore poor (67%). However, the specificity of DUSS compared more favourably with a value of 91%. Positive predictive values ranged from 33-100% but negative predictive values were more reliable with values of 91-100% at all time points post operatively. There were no type I leaks, or endoleaks requiring intervention which were missed on DUSS. Overall, there was a 'fair' level of agreement between the two imaging modalities using Kappa statistics. CONCLUSION: Although DUSS is not as sensitive as CT scanning in the detection of endoleak, no leaks requiring intervention were missed on DUSS in this study. DUSS is much cheaper than CT and avoids high doses of radiation. DUSS therefore remains a valuable method of follow up after EVAR and can reduce the need for repeated CT scans.

Aneurysm↗

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↗

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↗

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↗

Inhibition of neointima formation in an organ culture of human saphenous vein: a comparison of dual endothelin-converting enzyme/neutral endopeptidase and selective neutral endopeptidase inhibition.

PURPOSE: Endothelin-1 (ET-1) has been implicated in a variety of vascular pathologic conditions, although there is considerable controversy as to whether such effects are mediated by the ET-(A) or ET-(B) receptor. This study investigated whether inhibition of big ET-1 processing by inhibition of endothelin-converting enzyme (ECE) could, therefore, offer an alternative therapeutic strategy in the prevention of vein graft intimal hyperplasia. METHODS: Human saphenous vein (3 equal segments from 10 patients) were maintained in organ culture for 14 days with either 50 micromol/L CGS 26303 (a dual ECE/neutral endopeptidase [NEP] inhibitor), 50 micromol/L CGS 24592 (a selective NEP inhibitor), or vehicle (control). They were then processed for immunostaining and neointimal thickness measurements, and conditioned media was collected for enzyme-linked immunosorbent assay analysis. RESULTS: Neointimal thickness in the ECE/NEP-inhibited veins did not differ significantly from that of control segments. However, there was a highly significant augmentation in the NEP-inhibited segments, consistent with an inhibition of ET-1 degradation (median difference, 16.8; 95% CI, -23.5, -10.4; P =.002, Wilcoxon). ECE immunostaining was reduced in the ECE/NEP-inhibited veins, although ET-1 staining was also present. ET-1 expression was intense in the thickened neointimas of NEP-inhibited veins, which also showed significant ECE staining. Elevated levels of big ET-1 were measured in the ECE/NEP-inhibited veins, consistent with reduced ECE activity. However, mature ET-1 was still detectable in these segments. CONCLUSION: There is a requirement for potent and selective inhibitors of ECE to evaluate fully the potential therapeutic benefits of blocking ET-1 biosynthesis. The use of dual inhibitors complicates the interpretation of results, because the observed response is likely to be a combination of both ECE and NEP inhibition.

Aspartic Acid Endopeptidases↗

A new fracture of the forearm adjacent to a healing fracture.

A 10-year-old girl sustained closed fractures of the distal radius and ulna. This was manipulated and she was treated in an above-elbow plaster for 4 weeks. Two weeks later she was discharged, only to have a second injury to the same forearm. X-ray showed a new fracture distal to undisrupted callus.

Accidental Falls↗

Raised levels of plasma big endothelin 1 in patients with colorectal cancer.

BACKGROUND: The aim was to assess the role of plasma Big Endothelin (ET) 1 levels as a marker of disease presence and stage in colorectal adenocarcinoma. METHODS: Big ET-1 was measured in the plasma of 37 patients with colorectal cancer. Preoperative systemic plasma levels of Big ET-1 in patients with cancer were compared with levels in 20 age- and sex-matched controls. Portal plasma samples were collected at operation in addition to peripheral venous samples. Immunohistochemical staining for Big ET-1 was performed on a selection of primary tumour specimens and liver metastases. RESULTS: Median (range) preoperative systemic plasma levels of Big ET-1 were significantly higher in patients with cancer than in controls (1.0 (0.3-9.7) versus 0.2 (0.0-6.0) fmol/ml; P = 0.0001). Intraoperative portal plasma levels of Big ET-1 were significantly higher in patients with Dukes' 'D' disease than in patients with Dukes' A, B and C disease (2.1 (1.4-10.0) versus 1.2 (0.3-6.6) fmol/ml; P = 0. 01). Similarly, systemic plasma levels were significantly higher in patients with Dukes' 'D' disease than in those with localized disease (1.9 (1.2-9.7) versus 1.2 (0.2-8.3) fmol/ml; P = 0.01). The presence of microvascular invasion in the tumour specimens was associated with a significantly raised portal plasma level of Big ET-1 (1.6 (1.5-2.1) versus 1.1 (0.8-1.3) fmol/ml; P = 0.04). Immunohistochemistry localized Big ET-1 to the cancer epithelial cells. CONCLUSION: The plasma level of Big ET-1 is significantly raised in patients with colorectal cancer. Patients with liver metastases have significantly higher levels than those with localized disease.

Adenocarcinoma↗

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↗

The clinical management and outcome of venous ulcers in legs with deep-venous obstruction.

OBJECTIVE: as a result of a serious complication from compression bandaging in a patient with venous ulceration and deep-vein obstruction, a policy of incremental compression in such limbs has been developed. The purpose of this retrospective study is to review the outcome of this policy. DESIGN: limbs with deep-venous obstruction (stenosis or occlusion) were treated initially with 3-layer compression bandaging and reviewed 24 h later. If 3-layer bandaging was tolerated, it was re-applied for a further 48 h. If there were no problems, then 4-layer bandaging was applied and the patient reviewed at 24 and 72 h. If 4-layer bandaging could not be tolerated, the limb was returned to 3-layer bandaging. RESULTS: of 325 limbs seen in a venous-ulcer clinic, 22 (7%) had deep-vein obstruction. Fifteen (68%) limbs were able to tolerate 4-layer bandaging, five (23%) could tolerate 3-layer bandaging and two limbs (9%) could only tolerate class 2 compression hosiery. The overall 1-year healing rate was 55%. There were no serious complications from bandaging. CONCLUSIONS: a protocol of incremental compression bandaging is safe in ulcerated legs with deep-vein obstruction and produces healing in up to 55% of cases.

Aged↗

Marimastat inhibits neointimal thickening in a model of human arterial intimal hyperplasia.

OBJECTIVE: matrix metalloproteases (MMPs) produced by vascular smooth-muscle cells (VSMCs) degrade extracellular matrix and facilitate the migration of these cells. This is a fundamental process in arterial intimal hyperplasia. This study investigated whether Marimastat (a selective but non-specific MMP inhibitor) can prevent intimal hyperplasia in cultured human internal mammary artery (IMA). MATERIALS AND METHODS: segments of IMA from 8 patients were prepared and cultured for 14 days in serum-supplemented medium (control) or in medium supplemented with Marimastat at 2 concentrations (treatment groups). The tissue was fixed, sectioned, stained and neointimal thicknesses measured by computer-aided image analysis. Further sections were cultured in the same manner and prepared for gel enzymography to quantify the production of MMPs. RESULTS: neointimal thickness was significantly reduced by Marimastat in a dose-dependent manner when compared to controls (p =0.008 Wilcoxon). Gel enzymography demonstrated a reduction in levels of MMP2 and MMP9. This was most significant for the active forms of the enzymes ( p =0.03). CONCLUSIONS: our results suggest that there is a potential therapeutic role for specific inhibition of the gelatinases in the prevention of human arterial restenosis.

Cells, Cultured↗

A comparison of colour duplex ultrasonography, papaverine testing and common femoral Doppler waveform analysis for assessment of the aortoiliac arteries.

OBJECTIVE: to study the "accuracy" of aortoiliac colour duplex ultrasonography. DESIGN: prospective study. SETTING: vascular laboratory, University Hospital. METHODS: a total of 25 aortoiliac stenoses were studied in 23 patients. For each iliac segment, colour duplex ultrasound, papaverine testing, hyperaemic common femoral Doppler waveform analysis and hyperaemic testing using a thigh pressure cuff were performed. A velocity ratio of two was used to indicate a significant 50% diameter-reducing stenosis, but the velocity differences across stenoses as well as various characteristics of the hyyperaemic common femoral waveform were also studied. Retrospective receiver-operator characteristics and Kappa values were used for analysis. RESULTS: the Kappa agreement between ultrasonography and papaverine testing was 0.12 using peak systolic velocity ratios and 0.8 using hyperaemic peak systolic velocity differences. Hyperaemic common femoral pulsatility (PI) and resistance index (RI) both gained a Kappa level of 0.60. The reactive hyperaemia produced by a thigh cuff was more pronounced than that produced by papaverine. CONCLUSION: although the velocity ratio did not appear to perform well against the papaverine test, its apparent over-sensitivity calls into question the sensitivity of papaverine testing itself. The hyperaemic velocity difference at the stenosis or the hyperaemic PI or RI at common femoral level appear useful, non-invasive indicators of significant aortoiliac arterial disease.

Aged↗

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↗

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↗

Antiproliferative effect of UTP on human arterial and venous smooth muscle cells.

We have investigated the hypothesis that responses associated with proliferation are regulated by extracellular nucleotides such as ATP and UTP in cultured human vascular smooth muscle cells (VSMC) derived from internal mammary artery (IMA) and saphenous vein (SV). Platelet-derived growth factor (PDGF), ATP, and UTP each generated an increase in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in both IMA- and SV-derived cells in the absence of detectable inositol 1,4,5-trisphosphate production. ATP alone had no effect on [(3)H]thymidine incorporation into DNA, but with a submaximal concentration of PDGF it raised [(3)H]thymidine incorporation in SV- but not IMA-derived cells. UTP alone also was without effect on [(3)H]thymidine incorporation or cell number. However, in both SV- and IMA-derived cells, UTP reduced the PDGF-stimulated [(3)H]thymidine response and PDGF-stimulated cell proliferation. This cannot be explained by an inhibitory effect on the p42/p44 mitogen-activated protein kinase (MAPK) cascade, since this response to PDGF was not attenuated by UTP. We conclude that, in human VSMC of both arterial and venous origin, UTP acts as an anti-proliferative regulator.

Adenosine Triphosphate↗