Closing the loop: a 21-year audit of strategies for preventing stroke and death following carotid endarterectomy.

The objective of this review was to identify causes of stroke/death after carotid endarterectomy (CEA) and to develop transferable strategies for preventing stroke/death after CEA, via an overview of a 21-year series of themed research and audit projects. Three preventive strategies were identified: (i) intra-operative transcranial Doppler (TCD) ultrasound and completion angioscopy which virtually abolished intra-operative stroke, primarily through the removal of residual luminal thrombus prior to restoration of flow; (ii) dual antiplatelet therapy with a single 75-mg dose of clopidogrel the night before surgery in addition to regular 75 mg aspirin which virtually abolished post-operative thromboembolic stroke and may also have contributed towards a decline in stroke/death following major cardiac events; and (iii) the provision of written guidance for managing post-CEA hypertension which was associated with virtual abolition of intracranial haemorrhage and stroke as a result of hyperperfusion syndrome. The pathophysiology of peri-operative stroke is multifactorial and no single monitoring or therapeutic strategy will reduce its prevalence. Two of the preventive strategies developed during this 21-year project (peri-operative dual antiplatelet therapy, published guidance for managing post-CEA hypertension) are easily transferable to practices elsewhere.

Reprinted article "Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature".

OBJECTIVES: To determine the role of carotid artery disease in the pathophysiology of stroke after coronary artery bypass (CABG). DESIGN: Systematic review of the literature. RESULTS: The risk of stroke after CABG was 2% and remained unchanged between 1970-2000. Two-thirds occurred after day 1 and 23% died. 91% of screened CABG patients had no significant carotid disease and had a <2% risk of peri-operative stroke. Stroke risk increased to 3% in predominantly asymptomatic patients with a unilateral 50-99% stenosis, 5% in those with bilateral 50-99% stenoses and 7-11% in patients with carotid occlusion. Significant predictive factors for post-CABG stroke included; (i) carotid bruit (OR 3.6, 95% CI 2.8-4.6), (ii) prior stroke/TIA (OR 3.6, 95% CI 2.7-4.9) and (iii) severe carotid stenosis/occlusion (OR 4.3, 95% CI 3.2-5.7). However, the systematic review indicated that 50% of stroke sufferers did not have significant carotid disease and 60% of territorial infarctions on CT scan/autopsy could not be attributed to carotid disease alone. CONCLUSIONS: Carotid disease is an important aetiological factor in the pathophysiology of post-CABG stroke. However, even assuming that prophylactic carotid endarterectomy carried no additional risk, it could only ever prevent about 40-50% of procedural strokes.

Reprinted article "Subintimal angioplasty of femoropopliteal artery occlusions: the long-term results".

The technique of subintimal angioplasty has been attempted on 200 consecutive femoropopliteal artery occlusions of median (range) length 11 (2-37) cm. The principle of the technique is to traverse the occlusion in the subintimal plane and recanalise by inflating the angioplasty balloon within the subintimal space. The technical success rate was 159/200 (80%) and was not significantly different for occlusions <10 cm (81%, n = 73), 11-20 cm (83%, n = 63) or >20 cm (68%, n = 23), p = 0.20. There were no deaths nor limb loss resulting from the procedure. The median (range) ankle-brachial pressure index increased from 0.61 (0.21-1.0) preangioplasty to 0.90 (0.26-1.50) postangioplasty. The actuarial haemodynamic patencies of technically successful procedures at 12 and 36 months were 71% and 58% respectively, the symptomatic patencies were 73% and 61%. A multiple regression analysis showed that smoking multiplied the risk of reocclusion by 2.70 (p < 0.001), each additional run-off vessel reduced the risk by 0.54 (p < 0.001) and the risk increased by 1.73 (p = 0.020) for every 10 cm of occlusion length. In conclusion, the technical success rate (80%) of subintimal angioplasty for femoropopliteal occlusions is unrelated to occlusion length and for all procedures, including technical failures, cumulative symptomatic and haemodynamic patencies of 46 and 48% can be achieved at 3 years. The factors influencing long-term patency were smoking, the number of calf run-off vessels and occlusion length.

Delayed presentation following accidental inhalation of a pushpin.

A previously fit and well 18-year-old woman presented to the accident and emergency department following referral by her general practitioner with a provisional diagnosis of appendicitis. The history obtained from the patient revealed the presence of a bitemporal headache with associated neck stiffness, photophobia and vomiting for approximately 1.5 weeks. The patient complained of abdominal pain localised to her right iliac fossa and anorexia for approximately 1 week. She also noted the presence of a cough productive of green sputum for 3 weeks. A chest radiograph was obtained which showed a large area of consolidation in the right lower lobe consistent with infection and a linear density in keeping with a metallic foreign body. Following review of the chest radiograph, the patient was interviewed further and recalled having inhaled a pushpin approximately 1 year before her presentation. Aspiration of foreign bodies is relatively common in children and is often associated with delayed diagnosis and high morbidity. To prevent delayed diagnosis, characteristic symptoms and clinical and radiological signs of foreign body aspiration should be checked in all suspected cases and a low index of suspicion for ordering additional imaging or using bronchoscopy for diagnostic purposes should be employed.

Vacuum welding of olivine.

Welding of olivine was demonstrated by grinding it in a ball mill in an atmosphere of about 2 x 10(-7) torr. Most of the sample adhered strongly to the container and grinding balls although adhesion in air is only slight. Similar adhesion should be expected on the lunar surface and may account for the roughness needed to explain the optical properties of the moon and the detail of the una 9 photographs.

Elemental compositions and ages of lunar samples by nondestructive gamma-ray spectrometry.

A gamma-ray spectrometry system with low background was used to determine the radioactivity of crystalline rocks, breccias, and fine material. Nuclides identified were (40)K, (232)Th, (238)U, (7)Be, (22)Na (26)A1, (44)Ti, (46)Sc, (48)V, (52)Mn, (54)Mn, and (56)Co. Concentrations of K, Th, and U ranged between 480 and 2550, 1.01 and 3.30, and 0.26 and 0.83 parts per million, respectively. Concentrations of thorium and uranium were those of terrestrial basalts, while the potassium concentrations were near values for chondrites. Products of low-energy nuclear reactions showed pronounced concentration gradients at rock surfaces. Concentrations of K and of (22)Na determined here were combined with concentrations of rare gases to estimate gas-retention ages and cosmic-ray exposure ages with ranges of 2200 to 3200 and 34 to 340 million years, respectively, for three rocks.

ESVS guidelines. Invasive treatment for carotid stenosis: indications, techniques.

The European Society for Vascular Surgery brought together a group of experts in the field of carotid artery disease to produce updated guidelines for the invasive treatment of carotid disease. The recommendations were rated according to the level of evidence. Carotid endarterectomy (CEA) is recommended in symptomatic patients with >50% stenosis if the perioperative stroke/death rate is <6% [A], preferably within 2 weeks of the patient's last symptoms [A]. CEA is also recommended in asymptomatic men <75 years old with 70-99% stenosis if the perioperative stroke/death risk is <3% [A]. The benefit from CEA in asymptomatic women is significantly less than in men [A]. CEA should therefore be considered only in younger, fit women [A]. Carotid patch angioplasty is preferable to primary closure [A]. Aspirin at a dose of 75-325 mg daily and statins should be given before, during and following CEA. [A] Carotid artery stenting (CAS) should be performed only in high-risk for CEA patients, in high-volume centres with documented low peri-operative stroke and death rates or inside a randomized controlled trial [C]. CAS should be performed under dual antiplatelet treatment with aspirin and clopidogrel [A]. Carotid protection devices are probably of benefit [C].

The needle catcher--a safer way to suture.

The needle catcher is a novel surgical instrument which has been developed in Belfast in conjunction with Queen's University Belfast that aims to reduce suture needle exposure and increase operator safety during suturing. The instrument was used to close wounds in 20 patients presenting to A&E in the Royal Group of Hospitals and to the plastic surgery service in the Ulster Hospital. This letter includes a technical description of the instrument, evaluation of needle exposure, comments from users, evaluation of the needle catcher and a discussion on the need for additional protection for medical staff in surgical based specialties where there is frequent exposure to blood, open wounds and sharps.

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.

Unstable carotid plaques exhibit raised matrix metalloproteinase-8 activity.

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

Large-scale purification of human islets utilizing discontinuous albumin gradient on IBM 2991 cell separator.

A new method is described for the large-scale purification of human pancreatic islets with a discontinuous gradient of bovine serum albumin formed on an IBM 2991 cell separator. Fifteen human pancreases were processed, and after density-gradient centrifugation, a mean of 2643 islets/ml pancreatic digest were recovered with a mean purity of 63% and contained in 430 microliter mean vol. Viability of gradient-isolated islets was compared with that of non-density-gradient islets (handpicked) and showed no difference in function. This technique allows isolation of intact, viable human islets of Langerhans of sufficient purity for potential human transplantation.

Successful reversal of diabetes in nude rats by transplantation of isolated adult human islets of Langerhans.

A method is described in which the viability of isolated adult human islets of Langerhans can be assessed in vivo. The Rowett nude rat, made diabetic with streptozocin (STZ), has been used as the islet recipient in these studies. Although these animals are athymic and are able to accept xenogeneic grafts for prolonged periods, they are very susceptible to dehydration and infection once made diabetic. Therefore, a considerably shortened diabetes induction period was used. The basis of the study was to prepare pure adult human pancreatic islets that were cultured for 48 h. Nude rats were given 80 mg/kg i.v. STZ during islet isolation and were transplanted with 800-1000 islets under the renal capsule at 48 h. To monitor islet function, animals were bled regularly for random blood glucose measurements and were given a glucose tolerance test at day 20. The kidney containing the graft was removed on day 21 to allow histological assessment of the graft and to confirm that glucose control was due to the transplanted islets and was not secondary to reversion of the animal's own islets. Seven rats were transplanted, and five were deemed to have received viable human islets. Two rats that received islets from the same donor did not reverse their diabetes and were found by histology to have vacuolated islet structures with scant insulin-staining tissue under the kidney capsule. This method allows a definitive judgment of the ability of isolated adult human islets to reverse diabetes.

The intravenous intralipid tolerance test.

The half-life of an intravenously injected bolus of intralipid 20% was measured in normal rats in order to asess its relationship to reticuloendothelial system (RES) activity. Groups of animals were studied following various treatments, and the results compared to measurement of carbon clearance in similar groups. The RES effects of silica and C parvum were confirmed by the carbon clearance test, but no effect was seen on the half-life of intralipid. Intralipid clearance was shortened by fasting and the administration of intravenous heparin, neither of which affected carbon clearance. It is concluded that the intravenous intralipid test has no place in the asessment of RES function.

Endotension--a late complication successfully treated by open repair.

Endotension is a late complication following endovascular treatment of abdominal aortic aneurysm (AAA). A 83-year-old male had a successful endovascular repair of a 5.6 cm diameter AAA. During the follow-up period it was marked that the aneurysm continued to increase in size, became 6.6 cm maximal diameter and pulsatile with no evidence of endoleak. On laparotomy no endoleak was identified and the graft was left in situ. Postoperatively and on follow-up the patient remains asymptomatic while the aneurysm continued to appear shrunk.

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.

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

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

Characterisation of aorto-iliac arterial stenoses in terms of pressure and flow.

Aorto-iliac stenoses were characterised in terms of pressure drop and flow velocity in a canine model and in patients with occlusive arterial disease. Pressure above and below the stenosis was measured intra-arterially and flow related measurements were made at rest and during reactive hyperaemia in the dog, and following papaverine administration in patients. The addition of flow velocity information to the pressure drop across a stenosis gave an increased separation of stenoses in the experimental animal and also in man.

Changes in Doppler ultrasound sonagrams at varying distances from stenoses.

The effect of different degrees of arterial stenosis on Doppler ultrasound sonagrams recorded from various distances downstream has been investigated in a canine model. It has been found that even mild stenoses give rise to considerable disturbances close to the stenosis, and that more severe stenoses give rise to greater disturbances which propagate further downstream. The distance the disturbances travelled was not related to stroke volume, and it was only for stenoses of 88% area reduction and greater that such disturbances ever propagated beyond one stroke-length. Quantitative assessment of moderate degrees of proximal stenosis using continuous wave Doppler ultrasound will not be reliable unless the distance between the major stenosis and the recording site is known.