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Biomedical subjects

C N McCollum

Publications and source records attributed to C N McCollum.

At least 73 records · Page 4Linked to original sources

Soluble P-selectin in hyperlipidaemia with and without symptomatic vascular disease: relationship with von Willebrand factor.

Soluble P-selectin (CD62P) may arise from platelets, the endothelium, or both, and raised levels are found in those with thrombotic disease and atherosclerosis. To determine whether these increased levels in atherosclerosis are related to hypercholesterolaemia, blood samples were obtained from 86 patients (43 with symptomatic vascular disease) attending a hypercholesterolaemia clinic, and 86 age- and sex-matched controls. Parallel measurement of endothelial cell product von Willebrand factor helped define the origin of sP-selectin. Using ELISAs, soluble P-selectin was higher (median 290 ng/ml, range 80-735, P < 0.05) in patients with vascular disease than in both patients with uncomplicated hypercholesterolaemia (median 210 ng/ml, range 55-550), and controls (median 190 ng/ml, range 48-500). Von Willebrand factor was raised in both patients with uncomplicated hypercholesterolaemia (115 +/- 26 IU/dl, P < 0.05) and patients with hypercholesterolaemia and vascular disease (129 +/- 32 IU/dl, P < 0.02) compared with controls (102 +/- 30 IU/dl). Levels of soluble P-selectin did not correlate with von Willebrand factor, total low-density-lipoprotein (LDL) or high-density-lipoprotein (HDL) cholesterol or triglycerides levels, blood pressure or smoking, but von Willebrand factor correlated with LDL cholesterol (r = 0.42, P < 0.05). We conclude that plasma lipoproteins are not a major influence on levels of soluble P-selectin.

Adult↗

Prognostic value of increased soluble thrombomodulin and increased soluble E-selectin in ischaemic heart disease.

Endothelial cell dysfunction is likely to be important in the pathophysiology of ischaemic heart disease and increased levels of endothelial cell markers soluble E-selectin and soluble thrombomodulin may reflect this damage. To determine whether increased levels of these markers were predictive of disease progression, we obtained plasma from 54 patients who had survived a myocardial infarction. Soluble E-selectin and soluble thrombomodulin were measured by ELISA. After 49 months, 24 patients had suffered an additional cardiovascular event such as a second myocardial infarction or requirement for arterial surgery. Soluble E-selectin was 60+/-30 ng/mL in patients who suffered an end-point and was 54+/-23 ng/mL in those without an end-point (p=0.43). Soluble thrombomodulin was 65+/-24 ng/mL in patients who suffered an end-point and was 49+/-19 ng/mL in patients who were free of an end-point (p=0.009). The major risk factors for atherosclerosis (hypercholesterolaemia, hypertension, smoking) or peak creatinine kinase levels were unable to predict the development of an end-point. Using life tables, soluble thrombomodulin had a significant effect on survival free of an end-point (p=0.011). We conclude that the measurement of soluble E-selectin is of limited value in epidemiological studies, and that raised soluble thrombomodulin is a new marker for the progression of atherosclerosis in patients with ischaemic heart disease.

Adult↗

Monitoring wound healing by odour.

A pilot study using electronic aroma detection was performed over a six-month period to assess the aroma of chronic non-healing venous leg ulcers and the effect of appropriate antibiotic therapy on modification of the aroma. Deep infection with pathogenic organisms was found on biopsy culture in 13 out of 15 patients. Odour analysis was performed at weekly intervals on the ulcer dressings using an AromaScan instrument. Data points on the aroma maps moved from their pre-treatment presentation. Alterations in aroma data correlated well with the progress of the ulcers. Aroma analysis is shown to be a potential tool in monitoring the progress towards healing of chronic venous ulcers.

Aged↗

An unusual complication of total knee replacement: a case report.

After total knee replacement a 57-year-old woman developed increasing pain in her left calf on exercise. This was due to erosion of the popliteal artery by a spur of cement. Removal of the spur with resection and Dacron grafting of the damaged section of the vessel cured her symptoms.

Bone Cements↗

Calcium alginate as haemostatic swabs in hip fracture surgery.

Blood loss as a consequence of internal fixation of intertrochanteric fractures of the proximal femur was measured in two groups to compare the haemostatic effect of calcium alginate fibre swabs with that of simple gauze swabs. The patients in the gauze swab group lost 139.4 +/- 9.6 mL per-operatively, whilst those in the alginate swab group lost 98.8 +/- 9.9 mL (P < 0.01). The post-operative suction drainage loss in the gauze group was 158.4 +/- 17.3 mL, and that in the alginate swab group was 96.6 +/- 11.7 mL (P < 0.01). This study shows that alginate swabs significantly decrease per-operative blood loss and post-operative suction drainage loss, and suggests that haemostatic swabs could have wider applications in orthopaedic surgery.

Aged↗

Soluble P-selectin in atherosclerosis: a comparison with endothelial cell and platelet markers.

von Willebrand factor and soluble thrombomodulin are established plasma markers of endothelial cell dysfunction, whilst beta thromboglobulin is an established plasma marker of platelet activity. Soluble P-selectin may be the product of either or both types of cell and levels of all four molecules have been previously found to be increased in atherosclerosis. To determine the relationship of soluble P-selectin to the endothelial cell and platelet products, we measured the four indices in a case control study of 55 patients with peripheral vascular disease and 55 age and sex matched controls. von Willebrand factor (p < 0.0001), beta thromboglobulin (p = 0.0006), soluble P-selectin (p = 0.0021) and soluble thrombomodulin (p = 0.021) were all raised in the patients. Soluble P-selectin correlated with beta thromboglobulin (r = 0.34, p = 0.019) but failed to correlate with either endothelial cell marker. Co-culture of endothelial cells in vitro with bovine thrombin resulted in increased levels of von Willebrand factor in the supernatants but levels of soluble thrombomodulin and soluble P-selectin were not enhanced. Exposure of endothelial cell monolayers to elastase resulted in different patterns of release of von Willebrand factor, soluble thrombomodulin and soluble P-selectin. We suggest that soluble P-selectin is unlikely to arise from the endothelium and may be a new marker of platelet activation in atherosclerosis.

Aged↗

The influence of smoking and of oral and transdermal nicotine on blood pressure, and haematology and coagulation indices.

Nicotine is helpful in stopping smoking but its influence on cardiovascular risk factors is incomplete. Our aim was to determine its effect on blood pressure, routine haematology indices, and coagulation indices relevant to thrombosis. Eighteen subjects were seen whilst smoking (cotinine levels 1119 +/- 414 ng/ml), again after stopping smoking but while using nicotine chewing gum and/or skin patches (392 +/- 198 ng/ml), and again when not using nicotine (cotinine undetectable). There were no significant changes in blood pressures, platelet count, mean platelet volume, viscosity or anti-thrombin III. However, white blood cell count (p = 0.003), lymphocyte count (p = 0.016), red blood cell count (p = 0.02), haemoglobin (p <0.001), fibrinogen (p <0.001) and von Willebrand factor (p = 0.001) all fell between the first and second samples (when still using nicotine) but not between the second and third samples (when off nicotine). Oral and/or transdermal nicotine does not influence blood pressure or the haematology and coagulation indices we have measured.

Administration, Cutaneous↗

Increased soluble P-selectin following myocardial infarction: a new marker for the progression of atherosclerosis.

Increased soluble P-selectin has been described in atherosclerosis, but the mechanisms for this and its clinical significance are unknown. In an attempt to clarify these points we measured soluble P-selectin and von Willebrand factor, an endothelial cell marker, by ELISA in 116 patients who had survived a myocardial infarction and in 116 matched controls. Raised levels of both soluble P-selectin (median 272 ng/ml, range 55-850 ng/ml vs 190 ng/ml, range 40-395 ng/ml) and von Willebrand factor (mean +/- SD 128 +/- 37 IU/dl vs 100 +/- 33 IU/dl; both P < 0.001) failed to correlate (r = 0.12), and soluble P-selectin failed to correlate with any of the major risk factors for atherosclerosis. A four-year follow-up of 68 of these patients revealed that soluble P-selectin was higher in the 33 (48%) who had suffered an additional cardiovascular event (e.g. subsequent myocardial infarction, arterial surgery; median 350 ng/ml, range 275-460 ng/ml) compared with those free of an end-point (270 ng/ml, range 140-400 ng/ml, P = 0.0012). We conclude that increased soluble P-selectin is unrelated to the risk factors for atherosclerosis but is a new marker of disease progression in patients who have survived a myocardial infarction.

Aged↗

Repeated exercise induces release of soluble P-selectin in patients with intermittent claudication.

Controversy exists as to whether exercise in patients with intermittent claudication causes a harmful biochemical effect associated with an ischaemia-reperfusion injury of skeletal muscle. We report on exercise-induced changes in neutrophil activation, soluble P-selectin and von Willebrand factor in 34 patients with intermittent claudication and 12 matched controls. Von Willebrand factor (vWF) showed a cyclical pattern of response to exercise in control subjects (rising from 103 +/- 8 to 119 +/- 7 U/dl); claudicants did not show this pattern but had higher levels of vWF throughout (p <0.03). There was no consistent pattern of response in neutrophil hydrogen peroxide production to exercise in either claudicants or control subjects. Soluble P-selectin levels increased after exercise, but this only reached statistical significance after repeated exercise in claudicants (rising from 320 +/- 28 to 357 +/- 28 ng/ml). This rise in soluble P-selectin after exercise may indicate progressive platelet activation which may contribute to the excess cardiovascular mortality that claudicants are prone to.

Adult↗

Screening for abdominal aortic aneurysm: a computer assisted cost-utility analysis.

OBJECTIVES: To evaluate the effects of introducing routine ultrasonic screening for the identification and elective surgical treatment of abdominal aortic aneurysms (AAA) at high risk of rupture in the U.K. population of men aged 65-74 years. DESIGN: A computer assisted simulation of an AAA screening programme. The simulation incorporated assumptions gleaned from the literature about the epidemiology of AAA and the costs of screening. In addition, up-to-date costings based on recent Manchester (U.K.) vascular surgery experience are used. SETTING: A dialogue between National Health Service commissioners and providers to explore the feasibility and desirability of introducing AAA screening. CHIEF OUTCOME MEASURE: Cost per quality adjusted life year (QALY) gained. MAIN RESULTS: The absolute cost (circa 1992/3) per QALY gained from screening for and treating aneurysms of > or = 6 cm in diameter of pounds 1500 (benefit not discounted). Offsetting current treatment costs of ruptured aneurysms gives a net additional cost per QALY of pounds 1300. Screening and treating aneurysms of > or = 5 cm leads to a cost per QALY gained exceeding pounds 20000. The findings are robust under sensitivity analysis. CONCLUSIONS: Routine screening for AAAs of size > or = 6 cm compares favourably in terms of cost per QALY gained with services such as breast and cervical cancer screening.

Aged↗

Neutrophil activation in jugular venous blood during carotid endarterectomy.

OBJECTIVES: Neutrophils may play an important role in cerebral ischaemia. We investigated whether neutrophil activation can be detected in cerebral venous blood during the mild cerebral hypoxia and reperfusion that occurs during carotid cross clamping and declamping for endarterectomy. DESIGN, SETTING AND MATERIALS: The ipsilateral jugular bulb was cannulated at operation in 16 patients undergoing carotid endarterectomy. Blood was taken immediately prior to and 30 seconds following internal carotid cross clamping; then immediately prior to, 30 s and 2 m following declamping. Blood was also taken from a peripheral vein in the foot. Intracerebral oxygen saturation (CsO2) was measured continuously by near infrared cerebral spectroscopy. Neutrophil activation was measured by flow cytometric detection of fluorescence to hydrogen peroxide in unstimulated cells and phorbol myristate acetate stimulated cells, and expressed as mean fluorescent intensity (MFI). OUTCOME MEASURES: Neutrophil activation and cerebral oxygenation. MAIN RESULTS: CsO2 fell from 68% (95% Confidence interval 64%-72%) to 63% (59%-68%) following carotid cross clamping (p < 0.05, repeated measures analysis of variance). This recovered slightly during the cross clamp period to 64% but only returned to preclamp levels following declamping (p > 0.05). Neutrophil hydrogen peroxide generation by stimulated neutrophils rose significantly from 0.79 mean fluorescent intensity (0.53-1.19) to 1.46 (0.98-2.20) but no there was no further rise following cross clamp release. There was no significant neutrophil activation in the peripheral samples. CONCLUSIONS: These results indicate that even mild cerebral hypoxia is associated with priming of neutrophils in cerebral venous blood.

Aged↗

Neutrophil elastase, von Willebrand factor, soluble thrombomodulin and percutaneous oxygen in peripheral atherosclerosis.

OBJECTIVES: To test the hypothesis that endothelial cell damage and hypoxia are related to the activity of neutrophil elastase in patients with peripheral atherosclerosis. DESIGN: A cross-sectional serological study in a tertiary referral, University Hospital. MATERIALS: Venous blood was obtained from 22 patients with peripheral vascular disease and an equal number of age and sex matched controls. METHODS: Neutrophil elastase and two markers of endothelial cell damage (von Willebrand factor and soluble thrombomodulin) were measured in plasma by ELISA. Hypoxia was measured by percutaneous oxygen (by oximeter) at the dorsum of the foot. RESULTS: Patients had higher von Willebrand factor, higher soluble thrombomodulin and higher elastase but lower percutaneous oxygen (all p < 0.001). In the patient's group, there were significant inverse correlates between von Willebrand factor and percutaneous oxygen (p = 0.004) and between soluble thrombomodulin and percutaneous oxygen (p = 0.011) while elastase correlated positively with soluble thrombomodulin (p = 0.023). CONCLUSIONS: Our data support the hypothesis that release of elastase from activated neutrophils relates to endothelial cell damage. This may contribute to hypoxia and may result in the deterioration in clinically assessed atherosclerosis.

Arteriosclerosis↗

Recent developments in cerebral monitoring--near-infrared light spectroscopy. An overview.

A recent development has been the resurgence of interest in the concept of near-infrared light spectroscopy as a method of monitoring cerebral perfusion. Although this technique has been in use for 40 years, the principle has been primarily employed in peripheral pulse oximetry. Infrared light of wavelengths 600-1300 nanometres (nm) penetrate human tissue to a depth of several centimetres. Within the human brain this light is attenuated by the chromophores oxyhaemoglobin, deoxyhaemoglobin and also oxidised cytochrome a3. Positioning a near-infrared light source and a photodetector in a side by side configuration detects light attenuated and reflected in a parabolic path through the scalp, skull and brain tissue.

Brain↗

Circulating endothelial cell/leucocyte adhesion molecules in ischaemic heart disease.

Increased levels of the endothelial markers soluble E-selectin (P = 0.011), soluble thrombomodulin (P < 0.0001) and von Willebrand factor (VWF, P < 0.0001) were found in 116 patients with ischaemic heart disease compared to an equal number of age- and sex-matched asymptomatic controls. In a multivariate analysis of the markers versus the major risk factors for atherosclerosis, VWF correlated with total cholesterol (P = 0.002) and E-selectin with sex (lower in women, P = 0.004) and triglycerides (P = 0.007). The data point to profound differences in the release mechanisms of these three endothelial cell products and suggests that further studies into the roles of these molecules in coronary artery disease are warranted.

E-Selectin↗