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Biomedical subjects

C P Shearman

Publications and source records attributed to C P Shearman.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1995

The effect of epidural anaesthesia on peripheral resistance and graft flow following femorodistal reconstruction.

OBJECTIVE: To determine the extent to which epidural anaesthesia influences peripheral resistance and graft blood flow following femorocrural reconstruction. DESIGN: Prospective, controlled study measuring blood flow, arterial pressure and peripheral resistance in femorocrural bypass grafts for 20 min following onset of epidural anaesthesia with 15ml of 0.25% bupivacaine. PATIENTS: Twenty patients undergoing femorocrural reconstruction for critical lower-limb ischaemia with in situ long saphenous vein, under general anaesthesia. Ten patients had epidural cannulae inserted preoperatively and injected with bupivacaine after completion of the graft. RESULTS: Peripheral resistance fell in all 10 patients receiving epidural anaesthesia from a mean (range) of 1.07 PRU (0.32-2.2) to 0.49 PRU (0.19-0.72), compared to control values of 0.95 PRU (0.39-2.0) to 0.91 PRU (0.41-1.51; P < 0.01, Wilcoxon). There was a tendency for blood pressure to fall in the study patients (not significant) but graft blood flow still increased from 98 ml min-1 (41-221) to 160 ml min-1 (101-250), compared to flow in the control patients of 101 ml min-1 (45-176) at baseline to 104 ml min-1 (56-168; p < 0.01) at 20 min. CONCLUSIONS: Epidural anaesthesia significantly decreases peripheral resistance and increases graft blood flow in femorocrural grafts and would appear, therefore, to be of benefit for patients undergoing femorodistal reconstruction.

Aged↗
PubMed1994

Microproteinuria predicts the severity of systemic effects of reperfusion injury following infrarenal aortic aneurysm surgery.

Noncardiogenic pulmonary dysfunction can be demonstrated in all patients following elective aortic aneurysm repair and is a cause of postoperative morbidity. Aortic clamping and reperfusion initiate a systemic inflammatory response producing endothelial damage and increases in vascular permeability. In the lung this is manifest as pulmonary edema and in the kidney as detectable increases in urinary protein excretion (microproteinuria). Immunoassay of low-level protein excretion appears to provide an index of the systemic effects of local reperfusion injury and may allow early prediction of complications such as pulmonary edema. Hourly urinary albumin and IgG excretion was measured in 40 patients undergoing infrarenal aortic aneurysm repair and expressed as ratios to urinary creatinine (albumin/creatinine ratio [ACR] and IgG/creatinine ratio [IgGCR]). These were compared to clinical outcome. Pulmonary dysfunction was assessed according to PaO2:FiO2 ratios and chest radiography. Within 180 minutes of beginning surgery all patients had significant increases in ACR and IgGCR. Ten patients who manifested respiratory dysfunction had significantly higher ACRs at 4 hours (median 84.8, 95% confidence intervals, range 47.7 to 136) than patients who made uneventful recoveries (median 16.6, 95% confidence intervals, range 7.9 to 31.7). IgGCR increases paralleled that of ACRs. Differences persisted for 24 hours. Urinary protein excretion rises rapidly during aortic surgery. The degree of increase appears to predict development of pulmonary dysfunction. This simple test may provide a rational basis for evaluation of therapeutic modalities to limit reperfusion injury in these patients.

Aged↗
PubMed1994

Pharmacological reduction of the systemically damaging effects of local ischaemia.

Many patients with intermittent claudication are encouraged to exercise. However, transient exercise-induced muscle ischaemia results in systemic vascular endothelial injury associated with increased vascular permeability manifest as an increase in urinary albumin excretion. Repetitive systemic vascular endothelial injury leads to accelerated atherogenesis and may explain the high cardiovascular mortality rate of claudicants. Oxpentifylline, a haemorheological agent, has recently been shown to prevent vascular endothelial injury in animal models. A double-blind, placebo-controlled, cross-over trial was undertaken to determine the effect of oxpentifylline on exercise-induced systemic vascular endothelial injury in 20 claudicants. Urinary albumin, expressed as a creatinine ratio (ACR), was measured before and 1 and 2 hours after standardised exercise following 1 week treatment with either active drug or placebo. Oxpentifylline reduced the median (range) 1 hour post exercise increase in ACR from 0.35 (-0.46-12.72) to 0.02 (-6.00-14.10) mg/mmol. (p = 0.030, z = 2.2 Wilcoxon rank sign test). These results confirm that local ischaemia is associated with a potentially deleterious systemic effect and that it may be possible to attenuate this pharmacologically. The clinical significance of this is yet to be determined.

Aged↗
PubMed1994

Falsely elevated ankle pressures in severe leg ischaemia: the pole test--an alternative approach.

Ankle-branchial pressure indices (ABPIs), measured by sphygmomanometer and Doppler probe, are an accepted index of chronic leg ischaemia. However, tibial artery sclerosis or calcification decreases compliance, producing falsely elevated cuff occlusion pressures. Arterial cannulation is invasive and impractical, but by elevating the foot and measuring the height at which the Doppler signal disappears, ankle systolic pressure in mmHg can be derived. Using an 8MHz Doppler apparatus and calibrated pole, ankle systolic pressures measured by sphygmomanometer and elevation were compared in 49 severely ischaemic legs (40 patients). ABPIs were derived by dividing ankle systolic pressure by brachial pressure. Median (interquartile range) ABPI assessed by sphygmomanometry was 0.46 (0.35-0.56). Median ABPI measured by leg elevation was significantly lower at 0.21 (0.14-0.30), p < 0.0001, Wilcoxon. In 20 patients undergoing in situ vein bypass grafting, direct transducer-derived pressure measurements were obtained. Median ABPI for this method was 0.15 (0.11-0.27). No significant difference was found when compared with ABPIs derived by elevation, median 0.2 (0.13-0.31), p = 0.324, however median ABPI measured by sphygmomanometry was significantly higher at 0.37 (0.27-0.6), p = 0.0008. Correlation of elevation with transducer-assessed pressure measurements (r = 0.88) was closer than with cuff-derived measurements (r = 0.69). Pressures derived by leg elevation provide a more accurate index of severe leg ischaemia than sphygmomanometry, although the technique is limited to assessing pressures of less than approximately 60 mmHg. Falsely elevated ABPIs may underestimate the extent of disease in patients assessed for vascular reconstruction.

Aged↗
PubMed1994

Chronic muscle stimulation improves ischaemic muscle performance in patients with peripheral vascular disease.

There is currently no established treatment for intermittent claudication with proven long term benefit. Exercise classes have been shown to improve walking distance. Chronic electromyostimulation (CEMS) a method of stimulating skeletal muscle has effects on normal muscle which may also benefit claudicants. We investigated the effects of one month of CEMS on claudicants in a single blind placebo controlled study. Patients were randomised to either CEMS (treatment) or transcutaneous nerve stimulation (TENS) placebo. The effects of the two modalities were assessed using the conventional measures of claudicating distance (CD), maximum walking distance (MWD), ankle-brachial pressure index (ABPI) and pressure recovery time (PRT). Muscle performance was assessed by the fatigue index (FI) a technique determining the decrease in ischaemic muscle response to repeated contraction. After 4 weeks treatment the CEMS group showed significant improvements in their median CD (88 to 111) and MWD (118 to 158); this was not seen in the control group. Muscle performance also increased significantly during the 4 weeks of treatment in the CEMS group but not in the control group. These changes were not maintained after CEMS was stopped. This pilot study suggests that CEMS may well have a role to play in the treatment of intermittent claudication though a number of further studies need to be undertaken.

Aged↗
PubMed1993

Intermittent claudication incites systemic neutrophil activation and increased vascular permeability.

Reperfusion following severe ischaemia incites a systemic response involving neutrophil activation and vascular injury. Recent work suggests that intermittent claudication may also be capable of inducing similar changes, reversible by revascularization. This observation may have implications for the treatment of claudication and explain the high associated cardiovascular mortality. This hypothesis was investigated using an in vivo model. Rats underwent repeated hindlimb stimulation after common iliac artery ligation. Intravital fluorescence microscopy was used to observe postcapillary venules of the tibialis anterior muscle in the hindlimb. This revealed a bilateral increase in leucocyte-endothelial adhesion and vascular permeability to albumin after unilateral subtotal ischaemia and muscle stimulation, associated with increased urinary albumin excretion. These results provide further evidence supporting the association of intermittent claudication with potentially deleterious systemic manifestations.

Animals↗
PubMed1993

Ultrasonographic screening for abdominal aortic aneurysm in an urban community.

As part of the Birmingham Community Aneurysm Screening Project, 3500 men aged 65-75 years from 20 urban general practices were invited for aortic ultrasonographic screening at their own general practitioner's surgery; 2669 (76.3 per cent) attended. Compliance rates varied between catchment areas, from 52.1 per cent for inner-city areas to 89.6 per cent for suburbs. Successful aortic imaging was achieved in 97.3 per cent of scans. Aortic diameter > 29 mm occurred in 219 patients (8.4 per cent) and 79 (3.0 per cent) with a diameter > 40 mm were referred for vascular surgical assessment; 140 patients with an aortic diameter of 29-40 mm are currently undergoing follow-up by serial ultrasonographic examinations at intervals of 3 months at their doctor's surgery. Risk factor analysis revealed ischaemic heart disease in 21.9 per cent of men with aneurysm, compared with 11.6 per cent in those without (P < 0.001); 18.3 per cent of men with aneurysm had had a previous myocardial infarction and 13.2 per cent had peripheral vascular disease, compared with 7.4 per cent (P < 0.001) and 8.0 per cent (P < 0.01) respectively of those without. No association was found between aneurysm and hypertension or diabetes. Community-based aortic screening is an inexpensive, effective method of diagnosis of aneurysm, with high compliance from the at-risk cohort of an urban population. Such screening programmes may help to reduce the mortality rate from aortic aneurysm rupture.

Aged↗
PubMed1993

Reperfusion plasma contains a neutrophil activator.

Aortic aneurysm repair produces inflammatory mediators, neutrophil activation, and remote organ injury. Reperfusion plasma from these patients produces microvascular injury in an ex vivo chemotactic model. This study investigates the mechanism of this injury. Vena caval blood was obtained before and 15 minutes after aortic clamp removal (n = 16) or at laparotomy (n = 10). Plasma or saline solution was introduced into unit dose chambers fixed atop dermabrasions on the back of depilated anesthetized rabbits. Animals were treated with intravenous saline solution (n = 4); made neutropenic with nitrogen mustard (n = 4); pretreated with the xanthine oxidase inhibitor allopurinol (n = 4); or cotreated intravenously with the free radical scavengers superoxide dismutase (SOD) and catalase (n = 4). Three hours later neutrophil counts (polymorphonuclear cells [PMN]/mm3) and activity (free radical production by flow cytometry), protein leakage, and inflammatory mediators (thromboxane [TX] and leukotriene B4 [LTB4]) were measured. In contrast to control plasma in untreated rabbits, reperfusion plasma produced TX and LTB4 generation (1090 +/- 105 and 794 +/- 91 pg/ml, respectively, p < 0.01), PMN accumulation (1636 +/- 210/mm3, p < 0.01) and activation (276 +/- 31 mean fluorescent units), and microvascular permeability (554 +/- 90 micrograms/ml, p < 0.01). Neutropenia (3 +/- 1 PMN/mm3) and cotreatment with SOD and catalase abolished these responses, whereas pretreatment with allopurinol did not. Human reperfusion plasma contains a soluble factor that stimulates free radical generation by rabbit neutrophils to produce a microvascular injury characterized by de novo TX production, neutrophil accumulation and activation, and increased microvascular permeability to protein.

Allopurinol↗