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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
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↗
PubMed1998

Shortening and reimplantation for tortuous internal carotid arteries.

PURPOSE: The purpose of this study was to assess the outcome after the shortening and reimplantation of tortuous internal carotid arteries to prevent kinking after endarterectomy. METHODS: Through a review of prospective records, we studied patients who underwent carotid endarterectomy (CEA) (n = 233) between 1993 and 1996 who had symptomatic stenosis of the internal carotid artery (ICA) of more than 70%. An elongated proximal ICA was excised, and the ICA was reimplanted into the bifurcation in 30 (13%) patients, with additional patch angioplasty in 5 patients. Of the remaining 203 patients, 50 (21%) had Dacron patch angioplasty, and the rest had conventional CEA with simple closure. RESULTS: In the reimplanted group, one patient had a minor stroke with complete recovery on discharge. Three patients (10%) had neck hematomas requiring reexploration, but in none of these was the bleeding from the artery. At mean follow-up of 15 months, 93% of the arteries were widely patent. Significant stenosis secondary to neointimal hyperplasia was detected in only two patients, for a restenosis rate of 6.7%, which is in line with other published reports. In the control group, 8 (3.9%) patients had perioperative transient ischemic attacks, 5 (2.5%) had strokes, and 13 (6.4%) had hematomas requiring evacuation. At follow-up, 14 (6.9%) of the arteries had restenosed. CONCLUSION: In carotid surgery, reconstructive techniques must be tailored to operative findings. Excision of a tortuous elongated proximal ICA with reimplantation is not associated with additional mortality or morbidity rates over those of conventional CEA alone and has the advantage of removing disease at the bifurcation. This procedure was carried out in 13% of our patients and should be a procedure with which the vascular surgeon is familiar.

Aged↗
PubMed1998

Increased levels of soluble tumor necrosis factor receptors in atherosclerosis: no clear relationship with levels of tumor necrosis factor.

Inflammatory mediators, such as tumor necrosis factor alpha (TNF), may be important in the pathogenesis of atherosclerosis. Interactions between TNF and its target cell(s) requires the presence of specific receptors on the latter. Plasma levels of the two soluble forms of these receptors (tumor necrosis factor receptors, (sTNFr)) and TNF itself were measured by ELISA in 20 patients with peripheral vascular disease (PVD), 20 survivors of a myocardial infarction, and 20 age and sex matched controls. Levels of the p55 variant of the sTNFr were unchanged but levels of the p75 variant were increased in both groups of patients (ANOVA both P < 0.01). TNF was also raised in both groups of patients (both P < 0.05) but levels did not correlate with either sTNFr. In atherosclerosis, increased levels of p75 sTNFr may be further evidence of inappropriate leukocyte activation but unlikely to modulate the effect of free plasma TNF.

Aged↗
PubMed1998

Evaluation of the HemoCue for measuring intra-operative haemoglobin concentrations: a comparison with the Coulter Max-M.

We compared haemoglobin concentration values obtained using a portable haemoglobinometer, the HemoCue, in the operating theatre with the results obtained by the Coulter Max-M in the laboratory. Haemoglobin concentrations were measured on 52 arterial blood samples obtained from 13 patients during aortic surgery, in theatre with the HemoCue and again by the Coulter Max-M. Twenty routine samples from the laboratory were also analysed by both methods. There was no significant difference between results, with a mean of 10.94 g.dl-1 and 10.90 g.dl-1 for the HemoCue and Coulter, respectively (p = 0.12, t = -1.99, df = 70). The limits of agreement of the two methods (mean difference +/- 2 SD) were -0.37 and +0.45 g.dl-1. The coefficients of repeatability of the 20 samples analysed in duplicate on each device were 0.26 g.dl-1 and 0.33 g.dl-1, respectively. The coefficients of variance were 0.74% (HemoCue) and 0.93% (Coulter). With adequate training and monitoring, the HemoCue provides comparable haemoglobin results for near-patient testing in theatre.

Aorta↗
PubMed1998

Rheological properties and function of blood cells in stored bank blood and salvaged blood.

The technique involving filtration of diluted blood enables the separate analysis of the flow properties of different cell subpopulations. This study was designed to assess the changes occurring in the flow properties and function of blood cells in stored bank blood and salvaged blood compared to patient blood in a given clinical situation. We measured hydrogen peroxide production by neutrophils and the filterability, through 5 microm Nucleopore filters, of isolated red blood cells and of diluted blood. Samples were obtained from patients undergoing aortic surgery and blood intended for transfusion: either salvaged during surgery or stored bank blood. Both salvaged and bank blood were much less filterable than patient blood, with reduced deformability of both red and white blood cells. However, salvaged blood contained highly activated neutrophils with a prolonged transit time of the 'fast-flowing' cells in the analysis compared to bank blood. Bank blood contained significantly more particles which acted as pore-blockers. Cells in bank and salvaged blood therefore have markedly abnormal flow and biochemical properties compared to patient blood.

Blood Banks↗
PubMed1998

Soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) in inflammatory vascular disease, atherosclerotic vascular disease, and in cancer.

Cell surface adhesion molecule expression is likely to be important in inflammation, atherosclerosis and cancer, and soluble forms of many of these molecules are present in plasma. We measured levels of the soluble form of platelet endothelial cell adhesion molecule-1 (sPECAM) by ELISA in the serum of 77 patients with frank atherosclerosis, 69 patients with inflammatory connective tissue disease, and 39 patients with cancer. Each group of patients was controlled by an equal number of age- and sex-matched healthy subjects. There was no difference between sPECAM in patients with atherosclerosis and their matched controls or between patients with connective tissue disease and their controls. However, sPECAM levels were lower (16.6 +/- 5.0 ng/ml, mean +/- SD) in patients with cancer than in their controls (21.1 +/- 4.4 ng/ml, P < 0.001). No differences were found in sPECAM levels between the major subgroups of each type of disease, or as a result of factors such as age, sex or smoking in the controls. In contrast to levels of many other soluble adhesion molecules, levels of sPECAM are not altered in inflammatory or atherosclerotic vascular disease and therefore appear to have little relevance in these conditions. However, there may be significant differences in sPECAM levels in patients with low levels in cancer. Additional investigations are therefore justified.

Adult↗
PubMed1998

Circulating von Willebrand factor antigen II in atherosclerosis: a comparison with von Willebrand factor and soluble thrombomodulin.

von Willebrand factor antigen II (vWFAgII) is the 100 kDa propolypeptide of endothelial cell marker von Willebrand factor (vWF). Our aim was to determine the relationship between vWFAgII and mature vWF and an additional endothelial cell marker, soluble thrombomodulin, in atherosclerosis. To do this, we measured levels of all three by enzyme-linked immunosorbent assay in plasma obtained from 24 patients with peripheral vascular disease (PVD), from 25 patients who survived a myocardial infarction [i.e. had ischaemic heart disease (IHD)], and from 47 age- and sex-matched controls. We found raised levels of vWFAgII in PVD (57.3 +/- 15.3 microg/dl; mean +/- standard deviation) and in IHD (53.4 +/- 19.2 microg/dl) compared with the controls (35.7 +/- 12.0 microg/dl; analysis of variance P < 0.001). Raised levels of vWf were found in both groups of patients but raised soluble thrombomodulin was found only in patients with PVD. Levels of vWFAgII correlated with those of vWf (r = 0.45, P < 0.001) but not with soluble thrombomodulin (r = 0.14, P = 0.17), nor any of the major risk factors for atherosclerosis. Our brief study reports raised levels of vWFAgII in atherosclerosis. This may, like that of vWf, be related to endothelial cell damage, although the incomplete correlation between the two implies different metabolic and/or release mechanisms.

Aged↗
PubMed1998

Soluble adhesion molecules, endothelial markers and atherosclerosis risk factors in abdominal aortic aneurysm: a comparison with claudicants and healthy controls.

Development of an abdominal aortic aneurysm (AAA) may be a product of generalised atherosclerosis. If that is indeed the case, we would expect similarities in various risk factors and other markers in common with occlusive peripheral arterial disease (peripheral arterial disease), and less congruity with healthy controls. To test this hypothesis, we recorded the major risk factors for atherosclerosis, two markers of endothelial dysfunction, and soluble adhesion molecules in 21 patients with an uncomplicated AAA free of symptomatic peripheral arterial disease, 42 patients with peripheral arterial disease, and 42 healthy controls who were matched, as a group, for age and sex. After adjusting for smoking, there were no significant differences in blood pressure, fibrinogen, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1 or lipoproteins between the groups. However, markers of endothelial integrity von Willebrand factor and soluble thrombomodulin were both higher (P < 0.05) only in peripheral arterial disease patients. Relative to the controls, platelet marker soluble P-selectin was increased in AAA (P < 0.01) and in the peripheral arterial disease patients (P < 0.05). Levels were higher in AAA patients than in peripheral arterial disease patients (P < 0.05). Our laboratory data suggest that the pathophysiology AAA and peripheral arterial disease are not identical.

Aged↗
PubMed1998

Circulating ICAM-1 and VCAM-1 in peripheral artery disease and hypercholesterolaemia: relationship to the location of atherosclerotic disease, smoking, and in the prediction of adverse events.

We examined the relationship of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) with smoking and hypercholesterolaemia in peripheral artery disease (PAD). Serum samples were obtained from 119 patients with objectively-proven PAD, 39 patients with hypercholesterolaemia but asymptomatic for PAD, and 132 age and sex matched asymptomatic controls. Using ELISAs, we found increased sICAM-1 and sVCAM-1 (both p <0.01) in the patients with PAD relative to the controls, but no significant change in patients with hypercholesterolaemia. However, the effect for sVCAM-1 was lost when smoking was entered as a covariate. Only sICAM-1 was higher in patients with PAD in the femoral/iliac arteries compared to the carotid arteries (p <0.05). In a 39-month follow-up of 112 patients with PAD, increased ICAM-1 weakly (univariate p <0.05) predicted those 57 whose disease progressed (i.e. to end points such as myocardial infarction and arterial surgery). However, high fibrinogen was a much better (univariate p = 0.001, multivariate p <0.05) predictor of disease progression. We suggest (i) that increased levels of sVCAM-1 in atherosclerosis are due to smoking, (ii) that increased sICAM-1 is independent of this risk factor, (iii) that both these changes are independent of hypercholesterolaemia, and (iv) that increased sICAM-1 is a weak predictor of disease progression in peripheral atherosclerosis.

Aged↗
PubMed1998

The influence of acute smoking on leucocytes, platelets and the endothelium.

Cigarette smoking is a risk factor for the development of atherosclerosis. Possible mechanisms for this include leucocytes and platelet activation, and/or damage to the endothelium, any of which may contribute to changes in thrombosis and haemostasis. We examined the acute effects of smoking on these systems by obtaining blood before, immediately after, and at 10 and 30 min after the rapid smoking of two cigarettes in sequence by 20 smokers. Blood samples taken at the same time points from ten non-smokers acted as control material. In the smokers there was a transient rise in leucocyte count and neutrophil activation, but von Willebrand factor (VWF--marking endothelial damage) increased steadily at each time point (P <0.05). There were no changes in neutrophil elastase, soluble intercellular adhesion molecule-1 (sICAM-1 normally increased in smokers), fibrinogen, platelet count or soluble P-selectin (marking platelet activation, also normally increased in smokers). We conclude that the acute smoking of two cigarettes in succession will activate leucocytes and cause endothelial cell damage, but will not immediately influence platelet activity.

Adult↗
PubMed1997

von Willebrand factor and soluble E-selectin in the prediction of cardiovascular disease progression in hyperlipidaemia.

Two specific endothelial cell products, von Willebrand factor and soluble E-selectin, were measured together with serum lipids, lipoprotein(a), systolic and diastolic blood pressure (SHP, DBP) in a follow up study of 162 patients attending a dedicated lipid clinic. Patients were further classified by the presence or absence of symptomatic vascular disease and smoking. After a mean of 49 months, 45 patients experienced a cardiovascular event (fatal or nonfatal myocardial infarction, stroke, or arterial surgery) and 11 developed non-cardiovascular diseases, including cancer. In univariate analysis, existing vascular disease (P < 0.01), increased levels of von Willebrand factor (P < 0.0001) and low density lipoprotein cholesterol (P < 0.02), greater age (P < 0.01), and lower levels of soluble E-selectin (P < 0.03) were all predictive of future vascular events. However, in multivariate analysis, only increased von Willebrand factor was predictive (P < 0.001). von Willebrand factor was also higher in patients who developed non-cardiovascular disease relative to those free of disease (P < 0.05). Our data support the hypothesis that increased levels of von Willebrand factor are an indicator of poor prognosis in patients with atherosclerosis or its risk factors.

Adult↗
PubMed1997

Von Willebrand factor and soluble E-selectin in hyperlipidaemia: relationship to lipids and vascular disease.

Our objective was to determine whether endothelial cell products von Willebrand factor and soluble E-selectin are related to serum lipids, lipoprotein (a), and vascular disease in patients with hyperlipidaemia. In order to achieve our aim, blood samples were obtained for four experiments from 1) 160 patients (49 with symptomatic vascular disease) with hypercholesterolaemia and an equal number of age and sex matched controls; 2) 31 patients who were studied serially before and after successful resolution of their hypercholesterolaemia; 3) 15 patients with hypertriglyceridaemia; and 4) 20 controls, half of whom consumed a lipid-rich breakfast. von Willebrand factor and soluble E-selectin were measured by enzyme linked immunosorbent assay (ELISA) using commercial reagents. In experiment (1) von Willebrand factor was increased in the patients with hypercholesterolaemia (P=0.0077) and was higher still in patients with vascular disease (P<0.0001). Soluble E-selectin was not influenced by hypercholesterolaemia or vascular disease. The correlation of von Willebrand factor with total and LDL cholesterol (both P<0.001) remained after both age and blood pressure were controlled. Experiment (2) showed that serial studies in patients over an average of 7 months a reduction in total cholesterol was associated with a reduction in von Willebrand factor (r=0.51, P=0.002). Experiment (3) demonstrated that von Willebrand factor was not increased in patients with hypertriglyceridaemia (median 8.9 mmol/L), and in experiment (4) a lipid-rich breakfast taken by fasted, healthy controls produced an increase in serum triglycerides (P<0.01) but did not influence von Willebrand factor over an 8 hour period. We conclude that von Willebrand factor, but not soluble E-selectin, is raised in hypercholesterolaemia and therefore may be a potential indicator of endothelial cell physiology in subjects with, or at risk of, atherosclerotic vascular disease.

Adult↗
PubMed1997

Pilot study of carotid surgery for acute stroke.

BACKGROUND: Carotid endarterectomy is usually delayed for 2 months following an acute stroke, but the stroke may progress or a further stroke may occur. A randomized pilot study of urgent carotid surgery for acute stroke was undertaken to assess the feasibility of a definitive multicentre trial. METHODS: Seven Manchester hospitals referred patients with acute stroke (less than 7 days previously), defined according to the Oxfordshire Community Stroke Project classification The carotid arteries were examined by portable continuous-wave Doppler ultrasonography. Patients with more than 50 per cent carotid stenosis on portable Doppler ultrasonography underwent colour duplex Doppler imaging. Patients with more than 70-99 per cent carotid stenosis were randomized to urgent carotid surgery or best medical care. RESULTS: A total of 593 patients were assessed over 2 years. Of these, 414 had acute stroke, of whom 380 had probable cerebral infarction. Complete ipsilateral internal carotid artery occlusion was most common in patients with total anterior circulation infarcts (33 (28 per cent) of 117), whereas severe ipsilateral (70-99 per cent) stenosis was most common in partial anterior circulation infarcts (25 (20 per cent) of 128). Only 16 patients (one total and 15 partial anterior circulation infarcts) were fit enough for surgery and consented to randomization. CONCLUSION: A definitive trial of urgent carotid surgery would need to screen large numbers of patients but could focus on patients with partial anterior circulation infarcts.

Acute Disease↗