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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
PubMed2006

Comparison of the pro-inflammatory potential of monocytes from healthy adults and those with peripheral arterial disease using an in vitro culture model.

We adapted a monocyte:endothelial cell co-culture model to investigate the pro-inflammatory potential of monocytes from patients with peripheral arterial disease (PAD). Isolated monocytes were cultured with human umbilical vein endothelial cells (HUVEC) for 24h, after which the ability of the HUVEC to recruit flowing neutrophils was tested. Development of a usable protocol required comparisons of primary HUVEC with cells that had been passaged and/or frozen and thawed, evaluation of optimal culture media and comparison of monocytes from freshly drawn and stored blood. We found, for instance, that expansion of HUVEC was assisted by inclusion of hydrocortisone, but this agent was withdrawn before the test phase because it reduced responses of HUVEC. Using the optimal practical protocol, we found great variation in the ability of monocytes from different donors to cause neutrophil adhesion. Slightly more ( approximately 20%) monocytes from patients with PAD adhered to HUVEC than monocytes from healthy controls, and the monocytes from PAD patients induced approximately 70% greater subsequent adhesion of neutrophils. Thus, we developed a functional model of inflammatory potential usable in clinically-related studies and found that patients with PAD had circulating monocytes with greater than normal ability to activate endothelial cells.

Cells, Cultured↗
PubMed2005

Existing delays following the presentation of ruptured abdominal aortic aneurysm allow sufficient time to assess patients for endovascular repair.

OBJECTIVES: The greatest benefit of endovascular AAA repair (EVAR) may be in the management of rupture (RAAA). However, the detailed anatomical assessment required for EVAR has lead to concerns of surgical delay and death during cross-sectional imaging. In this study, we prospectively assessed patients with RAAA and correlated time of hospital arrival with time of surgery or death to ascertain whether these concerns are justified. METHODS: All patients presenting with RAAA between October 2000 and December 2002 were included. The hospital arrival time, onset of surgery or time of death, were recorded, as were demographic and physiological parameters. RESULTS: One hundred consecutive patients were studied, median age 75 years (range 54-94). Seventy-nine patients underwent attempted conventional surgical repair and 21 were palliated. The median delay from arrival to operation was 159 min (range 16-1450 min). Mortality in the surgical group was not affected by the length of delay (p = 1.0) or by CT scanning (p = 0.34). The median time from arrival to death in the non-surgical group was 435 min (15 min-6 days). CONCLUSIONS: Most patients who present with ruptured AAA experience a significant delay prior to surgery. This study suggests it is safe to assess the majority of RAAA patients for EVAR.

Aged↗
PubMed2004

Time trends in the published risks of stroke and death due to endarterectomy for symptomatic carotid stenosis.

BACKGROUND: Large randomised trials performed in the 1980s and early 1990s showed that carotid endarterectomy (CEA) is beneficial for patients with recently symptomatic severe stenosis. Some surgeons have argued that the operative risk of stroke and death has fallen over the last decade due to refinements in operative technique, and that the indications for surgery should therefore now be broadened. Yet, studies of routinely collected data report higher operative mortality than in the trials, and surgical case series without independent post-operative assessment by a neurologist may not provide reliable data on stroke risk. METHODS: We performed a systematic review of all studies published between 1994 and 2001 inclusive that which reported the risks of stroke and death for symptomatic carotid stenosis, and compared the reported risks and patient characteristics with those in the ECST and NASCET and with our previous review of studies published prior to 1995. Pooled estimates of the operative risk of stroke and death were obtained by Mantel-Haenszel meta-analysis. RESULTS: Of 383 studies published between 1994 and 2001, only 45 reported operative risks for patients with symptomatic stenosis separately. The pooled operative risk of stroke and death reported in studies published by surgeons only (4.2%, 95% CI = 2.9-5.5, 34 studies) was significantly lower (p < 0.0001) than that in the ECST and NASCET combined (7.0%, 95% CI = 6.2-8.0), whereas the pooled risk reported in studies that involved neurologists was similar (6.5%, 95% CI = 4.3-8.7, 11 studies, p = 0.6). In contrast, operative mortality in ECST and NASCET was significantly lower than in other studies published between 1994 and 2001. By comparison with our previous review, when stratified according to involvement of neurologists, we found no evidence of a reduction in published risks of death or stroke and death due to CEA between 1985 and 2001. CONCLUSIONS: There is no evidence of a systematic reduction over the last decade in the published risks of stroke and death due to CEA for symptomatic stenosis. Operative risks in studies with comparable outcome assessment are similar to ECST and NASCET. The surgical data from the large trials are still likely therefore to be applicable to routine clinical practice.

Carotid Stenosis↗
PubMed2004

Is there enough information about foot care among patients with diabetes?

The United Kingdom has a diabetic population of approximately 1.2 million. It is estimated that approximately 15% of all patients with diabetes will develop a foot ulcer in their lifetime. Twenty-five percent of all patients with foot ulcers will have a major amputation. There have been several publications demonstrating a reduction in foot ulcer and amputation rate through a range of active educational programs and ways of improving patient awareness of the problem. The authors' study attempted to establish the amount of information patients with diabetes have about care of their feet. Of 110 patients recruited, 37 (33%) claimed they had never received any information about foot care. Of those who had received advice, approximately half had received information or had access to information over the previous 10 years. In the majority of cases, information had been given once only. In conclusion, 33% of patients with diabetes did not recall receiving any information about foot care.

Journal Article↗
PubMed2003

Predicting outcome in ruptured abdominal aortic aneurysm: a prospective study of 100 consecutive cases.

OBJECTIVES: Case selection for surgery in patients presenting with ruptured abdominal aortic aneurysms (RAAA) is often difficult. A previous retrospective review identified five pre-operative risk factors associated with mortality [J Vasc Surg 23 (1996) 123]. In this study we aimed to identify whether these criteria could be usefully applied prospectively in patients presenting with RAAA. METHODS: All patients presenting with RAAA from October 2000 to December 2002 were included. The criteria were recorded with the time they were available and the time surgery commenced. The decision to operate was made on clinical grounds and no patient was refused surgery on the basis of these criteria. RESULTS: One hundred consecutive patients were studied, median age 75 (range 54-94). The operative mortality was 32.9% (26/79 patients). Surgical mortality increased with the number of positive criteria and was 8% (2/24), 24% (7/29), 55% (11/20) and 100% (6/6) for scores, 0, 1, 2 and > or =3, respectively. Age and conscious level were available in every patient. However, an ECG, haemoglobin and creatinine results were only available in 94, 81, and 69%, respectively. CONCLUSIONS: The scoring system accurately predicted operative mortality. The score was available in the majority of cases and may help the surgeon give informed consent to patients and relatives prior to surgical intervention.

Aged↗
PubMed2002

C-reactive protein is elevated in symptomatic compared with asymptomatic patients with carotid artery disease.

OBJECTIVES: to investigate the level of inflammatory markers between symptomatic and asymptomatic carotid stenosis patients. DESIGN: cross-sectional study. MATERIALS AND METHODS: a prospective study of 137 consecutive patients, admitted electively for carotid endarterectomy during 1997-2000, was conducted. 125 patients had cerebrovascular symptoms: either stroke (neurological deficit >24 h), Transient ischaemic attack (neurological deficit<24 h) or amaurosis fugax. Twelve patients were asymptomatic. A medical history and a fasting venous blood sample were taken from each patient around 6 weeks before surgery. The plasma concentrations of cholesterol and of inflammatory markers; (high sensitivity C-reactive protein (hs-CRP), sICAM-1, sVCAM-1, sE-selectin) were determined. RESULTS: the concentration of hs-CRP in the symptomatic group (3.9 mg/L) was significantly higher than in the asymptomatic group (2.1 mg/L; p = 0.04). These concentrations were within normal range (<10 mg/L). sICAM-1, sVCAM-1, sE-selectin and total cholesterol concentrations were not different between the two groups. CONCLUSION: plasma hs-CRP was elevated in symptomatic compared to asymptomatic patients with carotid artery disease. High sensitivity C-reactive protein has been shown to be of prognostic value in a number of cardiovascular conditions and this study suggests it may be of value to identify patient at high risk of developing neurological deficits.

Aged↗
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↗