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Biomedical subjects

C N McCollum

Publications and source records attributed to C N McCollum.

At least 19 recordsLinked to original sources
PubMed2002

Economic evaluation of a randomized clinical trial of haemodilution with cell salvage in aortic surgery.

BACKGROUND: This study evaluated the costs of acute normovolaemic haemodilution (ANH) and intraoperative cell salvage (ICS) versus homologous blood transfusion in aortic surgery in a prospective multicentre randomized trial. METHODS: One hundred and forty-five patients were randomized either to standard transfusion practice (homologous) or to a combination of ANH and ICS (autologous). Costs for each inpatient admission were identified. Cell salvage costs were assigned on the assumption that 50 operations were done each year employing a trained cell salvage operator. The results were analysed statistically using bias-corrected bootstrap analysis. RESULTS: Patients who had transfusion of homologous blood received some 251 units and those having a homologous transfusion received 103 units (P = 0.008). There was no difference in morbidity, mortality and duration of hospital stay. Transfusion-related mean costs were similar at 340 UK pounds for patients having a homologous transfusion and 357 UK pounds for those receiving autologous blood (mean difference 17 UK pounds (95 per cent confidence interval [c.i.]--184 UK pounds to 174 UK pounds); P not significant). There was also no significant difference in mean overall costs: 5859 UK pounds for homologous and 5384 UK pounds for autologous transfusion (mean difference--475 UK pounds (95 per cent c.i.--2231 UK pounds to 1342 UK pounds)). Sensitivity analysis showed that costs remained similar for 20 and 150 operations per annum. Exclusion of a dedicated cell salvage operator reduced autologous transfusion costs but did not have a significant impact on overall cost. CONCLUSION: Autologous transfusion is cost neutral in aortic surgery even when surgical activity is low.

Adult↗
PubMed2002

Relationship between plasma markers of endothelial cell integrity and the Framingham cardiovascular disease risk-factor scores in apparently healthy individuals.

Separate reports have identified differences in plasma levels of the endothelial markers soluble E-selectin, von Willebrand factor (vWf) and soluble thrombomodulin in each of the major modifiable risk factors for atherosclerosis (smoking, hypertension and hypercholesterolaemia), and abnormal levels of some plasma markers predict various adverse cardiovascular events. However, it is unclear whether there is an increasing effect on the endothelium with a worsening risk-factor profile. We measured the three endothelial cell markers by enzyme-linked immunosorbent assay in the plasma of 200 subjects (mean age, 54 years; 58% men) free of the symptoms and clinical signs of atherosclerosis. Levels of the markers were then correlated with the Framingham coronary heart disease (CHD) and cerebrovascular disease (CVD) scores to help determine which (if any) may be useful as good laboratory predictors of future cardiovascular events in prospective epidemiological studies. vWf correlated with CHD (r(s) = 0.269, < 0.001) and CVD risk (r(s) = 0.331, P < 0.001), but soluble E-selectin correlated only with CHD risk (r(s) = 0.163, P = 0.021). We conclude that, of the three specific endothelial markers, vWf correlates most closely with the Framingham risk-factor prediction scores and therefore may be the better plasma endothelial marker of the future development of an atherothrombotic event.

Adult↗
PubMed2002

Evaluating the cost and efficacy of leg ulcer care provided in two large UK health authorities.

OBJECTIVE: This prospective study investigated the cost and efficacy of leg ulcer care over a three-month period during 1993, 1994 and 1999. It compared two health authorities (Stockport and Trafford) whose populations totalled 540,000. METHOD: All patients with active leg ulcers were invited to community leg ulcer clinics offering research-based innovations in care. Patients without significant arterial disease (ankle brachial pressure index less than 0.8) were treated with multilayer compression bandaging. RESULTS: The 42% healing rate reported in the original Stockport study was maintained at 40% in 1999, although the 65% healing rate achieved by the leg ulcer clinics in 1993 was not replicated, with rates falling to 46%. Following the opening of community leg ulcer clinics in Trafford, healing rates rose from 20% to 42%. The annual expenditure on leg ulcer care in Stockport increased from 65,545.56 Pounds to 83,344.30 Pounds, while in Trafford the cost of care dropped from 151,375.35 Pounds to 53,176.76 Pounds between 1994 and 1999. CONCLUSION: This study suggests that reductions in costs and improvements in healing rates can be sustained in a mature community leg ulcer clinic programme staffed by specialist leg ulcer nurses.

Aged↗
PubMed2001

Expression of cyclooxygenase isoforms in normal human skin and chronic venous ulcers.

Chronic venous ulcers are an example of abnormal wound healing showing chronic inflammation which together with the underlying vascular pathology results in delayed healing. Prostaglandins are among the most important mediators of inflammation. They have proinflammatory effects, predominantly by affecting the vasculature. Cyclooxygenase (COX) is the rate-limiting enzyme in prostanoid synthesis. It is present in two isoforms: COX-1 (constitutive cyclooxygenase) which is produced in the body to maintain normal haemostatic functions, and COX-2 (inducible cyclooxygenase), which is induced during inflammation in response to cytokines. Using immunoenzymatic labelling and western blot analysis, this study has shown that both COX-1 and COX-2 were up-regulated in chronic venous leg ulcers by comparison with normal human skin. De novo appearance of COX-2 in chronic venous ulcers was demonstrated, which is not seen in normal human skin. The main cellular sources of both COX isoforms are macrophages and endothelial cells. COX-2 is also produced by mast cells and fibroblasts. A COX radioimmunoassay showed up-regulation of COX activity in chronic venous ulcers compared with normal skin (p<0.05). Up-regulation of COX-1 in chronic venous leg ulcers could produce prostacyclin, which contributes to angiogenesis. Thus, inhibition of COX-1 by non-steroidal anti-inflammatory drugs (NSAIDs) could increase the local ischaemia and hypoxia associated with chronic venous ulcers. On the other hand, up-regulation of COX-2 is most likely responsible for the persistent inflammation in chronic venous leg ulcers. COX-2 selective inhibitors could therefore be effective in the treatment of chronic venous ulcers.

Blotting, Western↗
PubMed2001

Cerebral embolisation during modern cardiopulmonary bypass.

OBJECTIVES: Cerebral microembolisation still occurs during cardiopulmonary bypass and may cause both stroke and postoperative cognitive impairment. We investigated the frequency of cerebral embolisation during coronary artery bypass surgery with modern cardiopulmonary bypass and related these to ascending aortic atherosclerosis. METHODS: Transcranial Doppler monitoring for cerebral embolisation to both middle cerebral arteries was performed in 65 patients undergoing coronary artery surgery with non-pulsatile alpha-stat hypothermic bypass. Epicardial ultrasound imaging of ascending aortic atherosclerosis was performed in 14 patients. RESULTS: Thirty patients (56.9%) had more than 200 emboli entering the middle cerebral artery territories during surgery; most at the start of bypass and during defibrillation. Readjustment of aortic clamps and aortic cannulation also caused a large number of emboli which were probably particulate. Aortic disease was mild (mean plaque thickness 1 mm, interquartile range 0.9-1.2 mm) and did not relate to the number of cerebral emboli produced by aortic manipulation. CONCLUSIONS: Cerebral embolisation remains common during coronary surgery despite advances in filter and bypass pump technology. Aortic manipulation and clamping was associated with emboli but epicardial ultrasound imaging was of little help in its prediction.

Adult↗
PubMed2001

Unchanging attitudes to autologous transfusion in the UK.

Our aim was to assess changes in attitudes to autologous transfusion amongst surgeons over a 10-year period in response to scientific evidence, public awareness, published guidelines, management and the increasing cost of blood products. Surgeons across the north-west of England completed questionnaires on knowledge, experience and attitude towards autologous transfusion in 1990, 1994 and 1999. Main outcome measures were changes in knowledge, experience and utilization of autologous transfusion; perceived advantages of autologous transfusion, obstacles to its implementation in surgical practice and preferences for specific techniques (preoperative autologous donation, acute normovolaemic haemodilution, intraoperative and postoperative cell salvage). There has been little change in practice over 10 years. Many more surgeons were keen to employ autologous transfusion than were using it. Autologous transfusion was only used in general, orthopaedic and cardiothoracic surgery. Safety and patient preference were the main arguments for implementation and logistics the main obstacles. Autologous transfusion was used sporadically in surgical practice. Clinical trials are needed to guide clinicians in the choice of transfusion techniques.

Attitude of Health Personnel↗
PubMed2001

The influence of homologous blood transfusion on immunity and clinical outcome in aortic surgery.

OBJECTIVES: To evaluate the influence of homologous blood transfusion on immune responses and post-operative morbidity in aortic surgery. DESIGN: Analysis of the effects of homologous blood transfusion in 128 patients in a prospective randomised trial evaluating homologous and autologous blood transfusion in aortic surgery. MATERIALS AND METHODS: Blood sampled before and at five times after surgery was assayed for C-reactive protein (CRP), neutrophil elastase, TNF-alpha and IL-6. Transfusions, morbidity and mortality were recorded; factors associated with poor outcome were identified by logistic regression. RESULTS: homologous transfusion during surgery was required in 32 patients and precipitated an increase in neutrophil elastase (p=0.008) and TNF-alpha (p=0.015) but not IL-6 and CRP. Elastase peaked early in transfused patients at 41.27 (13.92-52.11) Deltang/ml by 2 h compared to a peak of 21.51 (10.64-31.13) Deltang/ml by 24 h in those who were not transfused. TNF-alpha peaked at 1.2 (0-4.33) Deltapg/ml by wound closure in transfused patients and at -0.1 (-2.05-2.52) Deltapg/ml by 2 h without transfusion. Intra-operative homologous transfusion was associated with increased mortality (p=0.01) and prolonged intensive care stay (p=0.03). Mortality increased with age (p=0.003) and was inversely related to the CRP peak (p=0.007). Prolonged surgery predicted post-operative complications (p=0.025). CONCLUSION: Homologous transfusion increased the inflammatory response to aortic surgery and was associated with mortality.

Aged↗
PubMed2001

Cerebral injury during cardiopulmonary bypass: emboli impair memory.

OBJECTIVES: Cognitive deficits occur in up to 80% of patients after cardiac surgery. We investigated the influence of cerebral perfusion and embolization during cardiopulmonary bypass on cognitive function and recovery. METHODS: Cerebrovascular reactivity was measured in 70 patients before coronary operations in which nonpulsatile bypass was used. Throughout the operations, middle cerebral artery flow velocity and embolization were recorded by transcranial Doppler and regional oxygen saturation was recorded by near-infrared spectroscopy. Cognitive function was measured by a computerized battery of tests before the operation and 1 week, 2 months, and 6 months after surgery. Elderly patients undergoing urologic surgery served as controls. RESULTS: Cerebrovascular reactivity was impaired preoperatively in 49 patients. Median (interquartile range) regional cerebral oxygen saturation fell during bypass by 10% (6%-15%), indicating increased oxygen extraction, whereas mean middle cerebral flow velocity increased significantly by a median of 6 cm/s (both P <.0001, Wilcoxon), suggesting increased arterial tone. More than 200 emboli were detected in 40 patients, mainly on aortic clamping and release, when bypass was initiated, and during defibrillation. Cognitive function deteriorated more in patients having cardiopulmonary bypass than in control patients having urologic operations but recovered in most tests by 2 months. Measures of cerebral perfusion (poor cerebrovascular reactivity, low arterial pressures, and flow velocity in the middle cerebral artery) predicted poor attention at 1 week (r = 0.3, P <.01, Spearman). Emboli were associated with memory loss (r = 0.3, P <.02, Spearman). CONCLUSIONS: Cognitive deficits were common after cardiopulmonary bypass. Occult cerebrovascular disease was more severe than expected and predisposed to attention difficulties, whereas emboli caused memory deficits. We believe this to be the first report of differing cognitive effects from emboli and hypoperfusion.

Aged↗
PubMed2001

Changes in endothelial, leucocyte and platelet markers following contrast medium injection during angiography in patients with peripheral artery disease.

Peripheral artery angiography, a common diagnostic procedure, may cause early and late adverse reactions, such as anaphylaxis, thrombosis and possible progression of the underlying arterial disease. To test the hypothesis that radiographic contrast medium may contribute to these events by adversely affecting the endothelium, leucocytes and/or platelets, 19 subjects undergoing angiography for the investigation and/or treatment of lower limb atherosclerosis were recruited. Blood was obtained from the external iliac vein before, and at serial intervals after, the injection of radiographic contrast medium into the ipsilateral femoral artery for diagnostic use. Markers of endothelial cell injury (von Willebrand factor (vWf)), platelet activation (soluble P-selectin) and leucocyte activation (neutrophil elastase and soluble L-selectin) were measured in citrated plasma. Soluble intercellular adhesion molecule-1 (sICAM-1) and thromboxane B(2), which are non-specific markers of inflammation, were also measured. Compared with the sample prior to angiography, levels of soluble L-selectin and sICAM-1 were reduced (p<0.02) immediately after passage of the last bolus of contrast medium. 15 min later, levels returned to normal but the level of vWf had increased (p<0.02). After 30 min, only levels of thromboxane B(2) were increased (p<0.05). The following day both vWf (p<0.01) and soluble P-selectin (p<0.05) were increased. These data point to both early and late effects of contrast medium on markers of endothelial, platelet and leucocyte function.

Aged↗
PubMed2000

Relationship between endothelial cell markers and arterial stenosis in peripheral and carotid artery disease.

Damage to the endothelium is an important component of atherosclerosis and can be quantified by measuring plasma markers, such as von Willebrand factor, thrombomodulin, intercellular adhesion molecule-1, and E-selectin. We hypothesized that increased levels of these markers would be related to objectively defined disease severity among patients with peripheral atherosclerosis or carotid atherosclerosis. To test this, we measured the markers by using ELISA in the plasma of 45 patients with intermittent claudication alone and in 53 patients presenting with transient ischemic attack. Disease severity in the former was by ankle-brachial pressure index and in the latter by ultrasound defined % stenosis. Any symptomatic dual disease or history or present coronary atherosclerosis warranted exclusion. Data were correlated according to Spearman's method. The only significant correlation was between von Willebrand factor and ankle-brachial pressure index (r = -0.39, p = 0.008). Our data suggest that von Willebrand factor is the most sensitive marker of peripheral atherosclerosis and that none of the plasma markers seems to be a useful marker of the degree of carotid artery stenosis.

Arteriosclerosis↗
PubMed2000

Expression of nitric oxide synthase isoforms and arginase in normal human skin and chronic venous leg ulcers.

Chronic venous ulcers, an example of abnormal wound healing, show chronic inflammation with defective matrix deposition which together with the underlying vascular pathology, result in delayed healing. L-arginine is known to be metabolized by one of two pathways: nitric oxide synthase (NOS), producing nitric oxide (NO), or arginase, producing ornithine. NO is involved in many pathological conditions including vascular and inflammatory disorders. This study therefore investigated the distribution, level and activity of NOS and arginase in chronic venous ulcers in comparison with normal skin, using immunocytochemistry, western blotting, and enzyme assays. The results demonstrated an increased distribution of both NOS and arginase in chronic venous ulcer tissue compared with normal skin, with inflammatory cells and vascular endothelial cells as the main sources. These data were confirmed by western blot analysis, which showed increased levels of both enzymes in chronic venous ulcers. Moreover, there was significantly increased activity of both total NOS (p<0.04) and inducible NOS (p<0.05) in chronic venous ulcer tissue compared with normal skin, and significantly increased activity of arginase (p<0.01) in chronic venous ulcer tissue in comparison with normal skin. NO is known to combine with hydroxyl free radicals forming peroxynitrite, a potent free radical which causes tissue destruction. NO overexpression in chronic venous ulcers may be involved directly or indirectly (through production of peroxynitrite) in the pathogenesis and delayed healing of chronic venous ulcers, through its effects on vasculature, inflammation, and collagen deposition. Arginase is known to enhance matrix deposition. Thus, increased levels of arginase in chronic venous ulcers could contribute to the pathogenesis of lipodermatosclerosis associated with chronic venous insufficiency, predisposing to the formation of chronic venous ulcers and also to matrix cuff formation around blood vessels.

Arginase↗
PubMed2000

Differences in free and total tissue factor pathway inhibitor, and tissue factor in peripheral artery disease compared to healthy controls.

Tissue factor (TF) is one of the major initiators of coagulation and raised plasma levels have been found in various cardiovascular diseases. TF activity is, however, regulated by tissue factor pathway inhibitor (TFPI), and alteration in levels of TF and/or TFPI may thus relate to thrombogenesis and atherogenesis. To investigate possible abnormalities in TF and free TFPI (i.e. unbound to TF) and total TFPI among patients with peripheral artery disease (PAD), we studied 42 patients (mean age 57, 35 men) with objectively proven (by ABPI/Doppler) disease and 42 age- and sex- matched healthy controls. TF, free TFPI and total TFPI were measured in citrated plasma by ELISA. TF was higher in the patients with PAD compared to controls (275+/-122 pg/ml versus 158+/-60, P<0.0001) but levels of total TFPI were lower in the patients (43+/-10 ng/ml versus 50+/-15, P=0.021). There was no significant difference in levels of free TFPI between patients and controls (7.2+/-1.5 ng/ml in controls, 7.5+/-1. 6 among patients, P=0.39). Within the control patients, levels of free and total TFPI were significantly correlated (Spearman r=0.51, P=0.001) but in the patients with PAD this correlation was poor (r=0. 21, P=0.178). We suggest that reduced levels of total TFPI and raised levels of TF may contribute to the process of atherogenesis and the increased risk of thrombosis among patients with cardiovascular disease.

Adult↗
PubMed2000

Gradual Hunterian ligation for infected prosthetic bypass.

OBJECTIVE: To review gradual snare occlusion for the management of complex or recurrent graft infection. PATIENTS AND METHODS: Medical records of patients treated with gradual snare occlusion following graft infection were reviewed for indication for operation, type of bypass and graft material used. In addition, infecting organism, grade of infection (Szilágyi) and outcome were recorded. RESULTS: Four femoropopliteal, two extra-anatomic (axillofemoral) and aortobifemoral bypasses were included in this study. All had chronic infection (Szilágyi grade III) with onset of 4 to 24 months and two of which were recurrent. The causative organisms were coagulase-negative staphylococci, Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus in three patients, with no organism isolated in the remaining cases. There was no loss of limb following gradual snare occlusion but there was only one death due to aortic stump rupture 2 weeks later. CONCLUSION: Gradual snare occlusion is an alternative for the management of chronic or recurrent graft infection.

Adult↗
PubMed2000

The contribution of the external carotid artery to cerebral perfusion in carotid disease.

PURPOSE: In the presence of carotid occlusion, the external carotid artery (ECA) becomes an important source of cerebral blood flow, especially if the circle of Willis is incomplete. The contribution of the ECA to hemispheric blood flow in patients with severe ipsilateral carotid stenosis has never been previously investigated. METHODS: One hundred eight patients were monitored during sequential cross-clamping of the external (ECA) and then ipsilateral internal carotid artery (ICA) during carotid endarterectomy using transcranial Doppler sonography (TCD) (Neuroguard CDS, Los Angeles, Calif), to measure middle cerebral artery blood flow velocity, and near-infrared spectroscopy, to measure regional cerebral oxygen saturation (CsO(2)) (Invos 3100A; Somanetics, Troy, Mich). RESULTS: On the ipsilateral ECA cross-clamp, the median fall in CsO(2) was 3% (interquartile range, 1%-4%; P <.0001). On addition of the ICA cross-clamp there was a further fall of 3% and a total fall of 6% (3%-9%; P <.0001). The median percentage fall in middle cerebral artery blood flow velocity on ECA clamping was 12% (4%-24%; P <.0001); on ICA clamping it was 48% (25%-74%; P <.0001). Falls in TCD on ECA clamping were greater with increasing severity of ipsilateral ICA stenosis. The correlation between CsO(2) and TCD on external clamping, although less strong than that on internal clamping, was statistically significant r = 0.32; P =.01; Spearman rank correlation). CONCLUSIONS: The falls in TCD and CsO(2) were of a similar order of magnitude and must therefore reflect a fall in cerebral perfusion. The ipsilateral ECA contributes significantly to intracranial blood flow and oxygen saturation in severe carotid stenosis.

Aged↗
PubMed1999

Neutrophil activation and severity of tissue hypoxia during tourniquet-induced forearm ischemia in man.

Neutrophil activation and adhesion to the endothelium are thought to be central in the inflammatory response to reperfusion after ischemia. This study explores whether the severity of tissue hypoxia can be related to a biochemical measure. Venous blood was sampled from 20 volunteers undergoing tourniquet-induced forearm ischemia for 10 min and subsequent reperfusion. Samples were analyzed for neutrophil count, neutrophil hydrogen peroxide generation measured by flow cytometry, plasma thromboxane (a marker of platelet activation), the endogenous antioxidant glutathione peroxidase, and thrombomodulin, a marker of endothelial cell damage. Forearm oxygen saturation by near-infrared spectroscopy was monitored throughout the experiment. Neutrophil hydrogen peroxide generation fell from an initial mean fluorescent intensity (MFI) of 0.91 +/- 0.07 to 0.77 +/- 0.09 (mean +/- SE) during ischemia (P < 0.05) and this reduction correlated with severity of hypoxia (r = 0.56, P < 0.01). Plasma levels of glutathione peroxidase were also reduced during ischemia (P < 0.05) whereas plasma thromboxane levels rose (P < 0.05). There were no significant changes in plasma levels of thrombomodulin or circulating neutrophil count. In conclusion, alterations in a measurement of neutrophil function reflect the changes in tissue oxygenation and may act as a biochemical predictor of the severity of an ischemic injury.

Adult↗
PubMed1999

von Willebrand factor and soluble thrombomodulin as predictors of adverse events among subjects with peripheral or coronary atherosclerosis.

Increased levels of the endothelial markers von Willebrand factor and soluble thrombomodulin have been identified as predictors of the development of adverse cardiovascular events. The purpose of this study was to determine which of these markers is the best predictor of such events. Both markers were measured using enzyme-linked immunosorbent assays in 111 subjects at high risk of cardiovascular disease (50 with peripheral atherosclerosis and 66 who had suffered myocardial infarction). After a mean of 46 months, a follow-up investigation was performed and cardiovascular end-points (myocardial infarction, stroke, measured progression of peripheral atherosclerosis, arterial surgery, etc.) were noted. Multivariate analysis revealed that both markers were independent predictors among the 54 subjects who suffered any one of the cardiovascular end-points (P < 0.01). However, only an increased level of von Willebrand factor predicted the outcome among the 39 subjects who suffered a myocardial infarction, stroke or arterial surgery (P < 0.05). We conclude that von Willebrand factor is a marginally better predictor of cardiovascular events than soluble thrombomodulin.

Aged↗