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Biomedical subjects

C P Shearman

Publications and source records attributed to C P Shearman.

At least 19 recordsLinked to original sources
PubMed1998

The evidence for exercise-induced inflammation in intermittent claudication: should we encourage patients to stop walking?

OBJECTIVES: To review clinical and experimental evidence that exercise to the onset of calf pain in patients with intermittent claudication results in an inflammatory response, and to consider whether repeated inflammatory events induced by therapeutic exercise training may lead to progression of atherosclerosis. METHODS: A literature search was performed to identify studies measuring biochemical markers of exercise-induced ischaemia-reperfusion injury in patients with intermittent claudication. Current theories of atherogenesis were reviewed and the use of acute-phase proteins as potential markers of vascular disease explored. RESULTS: Exercise to the onset of calf pain results in an inflammatory response with free radical formation, neutrophil activation and systemic vascular endothelial damage. Acute-phase proteins such as C-reactive protein and serum amyloid A protein have exciting potential use as stable biochemical markers of disease in claudication. CONCLUSIONS: Further studies are needed to determine the effect of long-term exercise training on exercise-induced inflammation in claudication. Early work suggests, in fact, that exercise attenuates this inflammatory response. If this were confirmed then it would support the clinical impression that exercise training is beneficial in terms of symptomatic improvement and cardiovascular health in patients with intermittent claudication.

Acute-Phase Proteins↗
PubMed1998

Biochemical and inflammatory changes in the exercising claudicant.

Intermittent claudication is an early manifestation of atherosclerosis in the leg. The prognosis for the claudicating limb is reasonably good, but patients have excess cardiovascular morbidity and mortality rates compared with a control population. Increasing evidence suggests that the calf pain experienced when walking followed by rest generates a low-grade inflammatory response. The cumulative effects of these individual events may have an adverse effect on the progression of atherosclerosis. A review of the literature was performed to identify studies measuring the exercise-induced inflammatory response in claudicants and to try to identify the role of cumulative inflammatory changes in the progression of atherosclerosis. The effect of exercise training on these markers is briefly explored. Walking until the onset of calf pain (ischaemia) followed by rest (reperfusion) results in the generation of oxygen-derived free radicals, neutrophil activation and a generalized increase in vascular permeability. Baseline levels of chronic inflammatory markers such as acute-phase proteins are elevated in claudicants compared with controls, suggesting that the transient acute inflammatory response has longer-term consequences. Therapeutic exercise training appears to lead to an attenuation of these inflammatory markers. Intermittent claudication can be considered as part of an inflammatory disease process. However, the concerns that exercise training might potentiate the vascular inflammatory response appear to be unjustified, although further work is needed to clarify this. Exercise training should therefore be considered as an important treatment option for claudication.

Arteriosclerosis↗
PubMed1997

Pharmacokinetics and pharmacodynamics of intra-graft iloprost in femorodistal bypass surgery.

Intra-graft injection of the prostacyclin analogue, iloprost, was performed at the end of femorodistal bypass procedures in 12 patients with severe peripheral arterial occlusive disease. Iloprost plasma levels were measured and compared with changes in haemodynamics. There was a high initial iloprost plasma level (mean 625 pg/ml) which dropped to a mean of 50 pg/ml after 15 min. This correlated with an immediate reduction in systolic blood pressure which had returned to pretreatment levels after 15 min. In contrast, the vascular resistance distal to the graft showed a reduction after 5 min which was maintained for at least 20 min after iloprost injection and the mean blood flow through the graft increased steadily throughout the same period of measurement. The study showed an effect of iloprost on blood pressure which correlated with plasma levels, but the time course of the changes in distal vascular resistance and graft blood flow demonstrated an effect more prolonged than the half-life of iloprost.

Aged↗
PubMed1997

Iloprost.

Explore the source record for details and available documents.

Drug Evaluation↗
PubMed1997

Exercise training for intermittent claudication: does it adversely affect biochemical markers of the exercise-induced inflammatory response?

OBJECTIVES: To identify a stable biochemical marker of disease severity in patients with intermittent claudication and to use these findings to assess the effect of therapeutic exercise training. DESIGN: Case-control study: prospective randomised-controlled trial of exercise training. MATERIALS AND METHODS: Plasma fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP) and urinary albumin-creatinine ratio (ACR) were measured in 67 claudicants and 15 controls. Twenty-two patients were randomised to supervised exercise training and 17 randomised to observation. Subjects were reviewed at 3, 6 and 12 months. RESULTS: The median (interquartile range) baseline fibrinogen was 3.7 g/l (3.3-4.25) in claudicants and 3.5 g/l (2.9-3.95) in controls (p = 0.045); CRP was 4.7 mg/l (2.2-9.0) and 2.1 mg/l (1.0-2.8), respectively (p < 0.0001); SAA was 72 mg/l (35-132) and 30 mg/l (20-89) (p = 0.0009). Claudicants showed an increased urinary ACR following treadmill exercise (Wilcoxon, p < 0.0001) with no change in controls. Exercise training reduced SAA at 6 months, CRP at 3 months and progressively attenuated the post-exercise increase in ACR. No similar changes were found in controls. CONCLUSIONS: Repetitive low-grade inflammatory events in claudicants lead to elevation of serum acute-phase proteins. Exercise training is associated with symptomatic improvement and reduction inflammatory markers. The concern that exercise has adverse systemic effects therefore seems to be unjustified.

Aged↗
PubMed1996

Antioxidant depletion during aortic aneurysm repair.

Ischaemia-reperfusion injury generates oxygen-derived free radicals leading to local and distant damage. A simple method of following oxidative activity is to measure the consumption of endogenous scavenging antioxidants; an enhanced chemiluminescent assay was used to study this phenomenon in 21 patients undergoing surgery for abdominal aortic aneurysm (AAA). Samples of peripheral venous blood were taken before induction of anaesthesia and then from a central venous line and the inferior mesenteric vein before, during, and after clamping of the aorta. Further specimens were taken from the central line at 2, 6 and 24 h after operation. Antioxidant concentration in the peripheral, central and inferior mesenteric blood were similar, indicating that anaesthesia and surgical dissection had no effect. Levels decreased significantly in central and inferior mesenteric blood during and after clamping, but returned to normal by 24 h. These results confirm ischaemia-reperfusion phenomena in AAA repair.

Aged↗
PubMed1996

Quality of life in patients with intermittent claudication.

OBJECTIVE: As intermittent claudication (IC) infrequently progresses to limb loss many clinicians adopt a conservative approach to treatment. Recently percutaneous transluminal angioplasty (PTA) has been applied to patients with IC. If this were to become the first line treatment for IC it would have major implications in terms of hospital facilities as well as cost. A measure is required, therefore, to decide on rationing of limited financial resources. "Quality of life" may be more influential in determining demand on services since objective medical criteria cannot give an insight into the patients feelings of well being. DESIGN: We applied the Nottingham Health Profile, by post, to a group of claudicants and age/sex matched controls. 70% responded from both groups. Claudicants who had recently received intervention were excluded, as were controls complaining of any leg pains on walking. RESULTS: The results showed that claudicants have greater perceived problems in the areas of energy, pain, emotional reactions, sleep, and physical mobility compared to controls (p < 0.05; Mann-Whitney Test). This was reflected by a significantly greater positive response rate to problems with activities of daily living (0.05 > p > 0.02; Chi-square Test) in the claudicant group. CONCLUSION: Because of the cost and resource implications of introducing measures such as PTA to the treatment of vast numbers of patients with IC, we suggest that trials are needed to compare various treatments using quality of life measurements in addition to traditional efficacy/safety parameters.

Activities of Daily Living↗
PubMed1996

Arm vein reconstruction for limb salvage: long-term outcome.

A series of 42 consecutive patients undergoing infrainguinal vascular reconstruction for limb salvage using vein harvested from the arm were followed prospectively to determine the long-term graft patency and stenosis rates. Vein harvested from the arm ('arm vein') was used for secondary or tertiary reconstruction in 22 patients (52.4%). The outflow was to a single calf vessel in 37 grafts (88.1%). The cumulative primary, primary assisted and secondary graft patency rates were 35.6%, 49.6% and 59.5% at 2 years, respectively, and the limb salvage rate was 69.0% at 2 years. Eight grafts developed stenoses detected by a graft surveillance programme. Six stenoses were dilated successfully with percutaneous transluminal angioplasty (PTA) and one was treated with an interposition vein graft. Bypass using arm vein is time-consuming and technically demanding as multiple anastomoses are often required. Arm vein grafts, however, have no greater incidence of stenosis than long saphenous vein grafts and these stenoses may be dilated with PTA with good results. The long-term outcome suggests that an arm vein graft is an important treatment option in the absence of the long saphenous vein.

Adult↗
PubMed1995

Antioxidant consumption during exercise in intermittent claudication.

Twenty male claudicant patients and nine age-matched controls were exercised on a treadmill. Blood and urine samples were taken before and after exercise. Total antioxidant concentration was measured using an enhanced chemiluminescent assay and microalbuminuria determined by radioimmunoassay. Claudicants had increased microalbuminuria after exercise. Mean (s.e.m.) antioxidant concentrations were similar for patients and controls at rest: 479(28) and 438(23) mumol/l respectively. Claudicants showed a significant decrease in antioxidant concentration 1 min after exercise to 428(27) mumol/l; this returned to 470(30) mumol/l by 10 min. A correlation was found between the decrease in antioxidant concentration and the increase in microalbuminuria (rs = -0.496, P < 0.05). This study supports the concept of ischaemia-reperfusion injury in claudicant patients and has implications for treatment.

Adult↗
PubMed1995

Thromboxane and neutrophil changes following intermittent claudication suggest ischaemia-reperfusion injury.

OBJECTIVES: It has been postulated that ischaemia-reperfusion occurs in intermittent claudication resulting in neutrophil activation and release of soluble mediators, increasing systemic vascular permeability and enhancing atherogenesis. METHODS: We measured neutrophil deformability, plasma thromboxane levels, and urinary microalbumin excretion in 30 male claudicants, and 10 age- and sex-matched controls, before and after exercise to maximum walking distance. Blood was taken from an antecubital vein. RESULTS: There was an increase in urinary microalbumin excretion after exercise in claudicants. Statistically significant increases in the median and 90th percentile transit times (markers of neutrophil deformability) for isolated neutrophils from blood drawn 5 min after exercise in the claudicants were observed with no change in control subjects. Plasma thromboxane concentrations in claudicants increased within 10 min post-exercise. Plasma concentrations in controls were significantly lower throughout the study period. In the claudicant group, a positive correlation between the percentage change in the median transit time for neutrophils, and the percentage change in plasma thromboxane at 60 min post-exercise was found. CONCLUSIONS: The results lend further support to the concept of ischaemia-reperfusion events in patients with intermittent claudication, leading to a systemic increase in vascular permeability as a result of endothelial injury or dysfunction (a crucial step in atherogenesis), associated with thromboxane production and neutrophil activation. We suggest that the above changes may contribute to the increased mortality seen in such patients.

Adult↗