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Biomedical subjects

J I Spark

Publications and source records attributed to J I Spark.

At least 19 recordsLinked to original sources

Hyperhomocysteinaemia is associated with the rate of abdominal aortic aneurysm expansion.

OBJECTIVES: Previous literature has suggested an association between AAA and the presence of elevated plasma homocysteine levels (HCY). Homocysteine can stimulate elastolysis in the arterial media via activation of elastase and matrix metalloproteinases. No evidence in the literature exists correlating aneurysm expansion and HCY. The study objective is to identify whether the rate of AAA expansion is related to HCY. METHODS: 108 patients undergoing surveillance for AAA were identified at our vascular surgical unit. AAA size and growth rate were assessed by serial ultrasonographic measurements. Fasting total HCY levels were measured using fluorescence polarisation immunoassays. Demographic details and atherosclerotic risk factors were noted all AAA patients. A multivariate analysis was performed for growth rate vs. HCY, hypertension and hypercholesterolaemia. The correlation between AAA growth rate, AAA size and HCY levels were calculated. RESULTS: 60% of patients with AAA had some degree of hyperhomocysteinaemia (> 15 micromol/l). Multivariate analysis showed HCY to be the only significant factor affecting AAA growth rate. A positive correlation was demonstrated between HCY levels and AAA growth rate using a linear regression model (R=0.28, p=0.003). Median growth rate among patients with hyperHCY was double that of patients with normal HCY (0.5 mm/month vs. 0.25 mm/month, p=0.003). A growth rate of > 10 mm/year was seen in 25% of hyper HCY patients and in only 2% of patients with normal HCY. In addition patients with hyper HCY and larger AAAs (> 4 cm) had a growth rate twice as fast as patients with hyper HCY and AAAs < 4 cm. CONCLUSIONS: A correlation between HCY and growth rate exists, although this is weak due to the multifactorial aetiology of AAAs. HyperHCY patients have faster expansion rates than patients with normal HCY, with significant numbers demonstrating rapid expansion (> 10 mm/year) and therefore an increased risk of rupture.

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Randomized clinical trial of intraoperative autotransfusion in surgery for abdominal aortic aneurysm.

BACKGROUND: Perioperative homologous blood transfusion (HBT) is associated with adverse reactions and risks transmission of infection. It has also been implicated as an immunosuppressive agent. Intraoperative autotransfusion (IAT) is a potential method of autologous transfusion. METHODS: This was a single-centre randomized clinical trial of IAT in surgery for abdominal aortic aneurysm. Forty patients were randomized to IAT and 41 underwent surgery with HBT only. Patients in both groups received HBT to maintain haemoglobin levels above 8 g/dl. Transfusion requirements, and incidence of systemic inflammatory response syndrome (SIRS) and infection, were compared. RESULTS: Significantly fewer patients in the IAT group required HBT (21 versus 31; P = 0.038) and the median blood requirement per patient was 2 units lower (P = 0.012). There was a higher incidence of chest infection (12 versus four patients; P = 0.049) and SIRS (20 versus nine patients; P = 0.020) in the HBT group. Risk of SIRS was related to aortic cross-clamp time in the IAT group only. CONCLUSION: Use of autotransfusion effectively reduced the need for HBT and was associated with a reduced incidence of postoperative SIRS and infective complications.

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The role of statins in vascular disease.

BACKGROUND: Recent publications have highlighted the benefits of statins in non-cardiac occlusive disease but also the failure of vascular surgeons to recognise and treat the risk factors for atherosclerosis, in particular hypercholesterolaemia. The aim of this review is to clarify the current experimental and clinical evidence for the use of statins in vascular disease. METHODS: Literature compiled from an extensive search of Medline and the Cochrane database has been used for the basis of this review. RESULTS: Experimental and clinical evidence consistently reports that statins improve endothelial dysfunction, are anti-inflammatory, anti-proliferative, anti-thrombogenic and anti-proteolytic. These effects are known to inhibit atherogenesis and improve plaque stability. Independent groups support the use of statins in the prevention of both primary and secondary cardiac events. The National Stroke association recommends their use to reduce strokes following myocardial infarction and the Heart Protection Study reports benefits in patients with non-cardiac occlusive disease. CONCLUSIONS: There is substantial evidence advocating the use of statins in patients with clinically significant vascular disease. In the future this may evolve to include those patients at risk from neointimal hyperplasia, aneurysmal disease and ischaemia reperfusion injury.

Cardiovascular Diseases↗

The incidence of hyperhomocysteinaemia in vascular patients.

INTRODUCTION: Hyperhomocysteinaemia has recently been identified as an important risk factor for atherosclerotic vascular disease. Screening for hyperhomocysteinaemia has been recommended, however, the incidence of hyperhomocysteinaemia in vascular patients is not known. AIMS: To determine the incidence of hyperhomocysteinaemia in vascular patients, to determine the relation of hyperhomocysteinaemia with folate, vitamin B12 levels and lipid profiles in vascular patients. To examine if there is a relationship between the degree of vascular injury and homocysteine concentration. METHODS: New vascular patients at The Queen Elizabeth Hospital were recruited and divided into peripheral, and aneurysmal presentations. Patients demographics were recorded, blood samples were taken for fasting lipid profile, and homocysteine concentration. Samples were also taken for vitamin B12, plasma and red cell folate levels. Sixty age and sex matched controls were included for comparison. RESULTS: One hundred and twenty-six patients have been recruited, (95 men and 31 women) with a median age of 68 years (61-74 years). The incidence of elevated homocysteine, and cholesterol levels was 33, 47 and 24%. The levels of vitamin B12 and folate were normal in all patients. Homocysteine was elevated in 27% of claudicants, 50% of patients with rest pain and 53% of patients with an aortic aneurysm. CONCLUSION: There is a high rate of hyperhomocysteinaemia in vascular patients with a higher incidence in patients with rest pain. There was also a high incidence of elevated homocysteine levels in patients with an abdominal aortic aneurysm. The rate of growth of these aneurysms is currently under review. Low folate or B12 concentrations is not the cause of raised homocysteine levels.

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How effective is acute normovolaemic haemodilution in femoro-distal bypass surgery?

BACKGROUND: Recent guidelines have emphasised the use of autologous blood in the surgical setting. The aim of this study was to analyse the efficacy and efficiency of acute normovolaemic haemodilution (ANH) as a blood conservation intervention in patients undergoing elective femoro-distal surgery for critical limb ischaemia. METHODS: Forty patients were studied prospectively. The volume of the blood collected was derived as follows: Blood volume removed = patient's blood volume (initial haematocrit - final haematocrit/average haematocrit) where final haematocrit is 30% and patient's blood volume is 70 and 65 ml/kg for a man and a woman, respectively. RESULTS: Twenty-five patients were suitable for ANH and 15 patients were excluded because of poor ventricular function, anaemia or renal disease. Nine of the 25 patients (44%) had <500ml of surgical blood loss and would have avoided homologous blood transfusion (HBT). Four of the patients lost >2000ml of blood and could not avoid HBT through ANH. Twelve patients had moderate blood loss (950-1400 ml), with eight of these patients requiring transfusion. Four patients avoided exposure to homologous blood. CONCLUSION: ANH is in evolution and as a single blood conservation intervention, contributes only modestly to blood conservation.

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Patients with chronic critical limb ischaemia have reduced total antioxidant capacity and impaired nutritional status.

INTRODUCTION: it has previously been demonstrated that total antioxidant capacity (TAC) can help predict which patients undergoing femoro-distal reconstruction are susceptible to postoperative infections. AIMS: the aims of this study were to examine if TAC is influenced by the nutritional state of the patient and the degree of ischaemia. PATIENTS AND METHODS: thirty patients with rest pain (21 men and 9 women), with a median age of 69 years and fifteen controls (9 men and 6 women), median age of 66 years, were studied. Nutritional status was assessed using serum albumin, body mass index (BMI), maximum voluntary contraction using a hand grip dynamometer and bioelectrical impedance to determine lean body mass. Blood was also taken for total antioxidant capacity (TAC). RESULTS: patients with chronic critical limb ischaemia (CCLI) had a lower TAC than controls (752 vs 1,130 micromol/l, p<0.05 Mann-Whitney U -test). There was no difference in serum albumin concentration between the CCLI group compared with controls (31 mmol/L vs 35 mmol/L, p>0.05 Mann-Whitney U-test). There was also no difference in BMI (23 vs 27, p>0.05 U-test) between the two groups. The other markers of nutrition including, maximum voluntary contractions (28.6 kg/m(2)vs 37.4 kg/m(2), p<0.05 M-W U-test), and lean body mass (3.0 vs 3.8 M-W U-test), showed a significant reduction in the vascular patients. CONCLUSION: TAC is significantly reduced in patients with CCLI and this may, in part, be explained by their impaired nutritional status.

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Role of the neutrophil in the development of systemic inflammatory response syndrome and sepsis following abdominal aortic surgery.

INTRODUCTION: There is evidence to suggest that the polymorphonuclear neutrophil (PMN) plays a critical early step in the development of the ischaemia-reperfusion syndrome, the systemic inflammatory response syndrome (SIRS) and sepsis. The PMN receptor CD16 plays an important role in phagocytosis, cell-mediated cytotoxicity and the release of free radicals and proteolytic enzymes. The aim of this study was to determine whether there is any relationship between PMN CD16 expression, phagocytosis and the development of sepsis. METHODS: Fifty patients who underwent elective infrarenal abdominal aortic aneurysm repair were studied. Venous blood was taken before operation, throughout surgery and for 7 days after operation. CD16 expression was measured, unstimulated and following further stimulation, by means of flow cytometry. Phagocytosis was determined using flow cytometry. RESULTS: Some 36 patients had an uncomplicated recovery; 14 developed SIRS or sepsis. There was no difference between the two groups with respect to nutritional, co-morbid or technical factors. In the group that developed septic complications after operation, the level of PMN CD16 expression was significantly higher before surgery (mean channel fluorescence (MCF) 30.2 versus 10.4; P < 0.05, Mann-Whitney U test) and throughout the postoperative period. Surgery produced no change in CD16 expression. After operation, stimulation of PMNs in the septic group resulted in a fall in CD16 expression (40.8 versus 20.4 MCF; P < 0.05, Mann-Whitney U test); surgery produced no change in the level of expression in the uncomplicated group. CONCLUSION: This study provides evidence of phenotypic and functional differences in neutrophil behaviour in patients who develop sepsis following aneurysm surgery.

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Epidemiology of abdominal aortic aneurysms in the Asian community.

BACKGROUND: Studies relating to the ethnic origin of patients with an abdominal aortic aneurysm (AAA) are few and are mainly concerned with the differences between black and white Americans. The purpose of this study was to determine whether the incidence of AAA among the Asian population of Bradford is different from that in the Caucasian population. METHODS: A retrospective study of patients with an AAA was carried out between 1990 and 1997 using data collected by the Patient Administrative Service, personal databases of the vascular consultants and theatre records. Information about the ethnic composition of the population of Bradford was obtained from the 1991 national census. Demographic data, including ethnic origin and clinical details, were obtained from patient notes. RESULTS: Two hundred and thirty-three patients with an AAA were identified during the study interval. The Asian population comprised 14.0 per cent of the total population of Bradford. Twenty-eight AAAs would be expected per year. All of the aneurysms identified occurred in the Caucasian population and none in the Asian community. CONCLUSION: These early results suggest that AAA is rare among the Asian population.

Age Distribution↗

Does angioplasty improve the quality of life for claudicants?: A prospective study.

This study aims to analyze the impact of percutaneous transluminal angioplasty (PTA) for claudication on patients' quality of life (QOL). The patients in this study included 108 claudicants, 74 men and 34 women, with a median age of 67 years (range 40-87 years), who were assessed prior to and at 1, 3, and 6 months following PTA. This is the first report to demonstrate that the previously well-documented improvements in the clinical indicators of lower-limb ischemia are accompanied by improvements in individual QOL domains and in overall global QOL. These findings are detectable within a month following PTA and last at least 6 months. The results of this study may go some way to provide proof of efficacy for the procedure and thus help justify the recently questioned widespread use of PTA in clinical practice.

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Does soluble intercellular adhesion molecule-1 (ICAM-1) affect neutrophil activation and adhesion following ischaemia-reperfusion?

OBJECTIVES: To examine the effect of reperfusion plasma and sICAM-1 on neutrophil integrin expression and neutrophil adhesion to determine if sICAM-1 has a potential role in the regulation of neutrophil adhesion. MATERIALS: Twenty-seven patients, 17 men and 10 women undergoing femorodistal surgery. Blood was taken preoperatively and from the femoral vein following the release of the cross-clamp. Neutrophils were obtained from five volunteers and incubated with phosphate buffered saline (PBS), preoperative plasma or reperfusion plasma with and without sICAM-1. Neutrophil expression of CD11b and adhesion were measured. MAIN RESULTS: Neutrophil CD11b expression did not change following incubation in the three media. Neutrophil adhesion increased significantly following exposure to reperfusion plasma compared to PBS or preoperative plasma (45.5 adhesion vs. 12.75%, p < 0.01 Mann-Whitney U-test). Soluble ICAM-1 decreased CD11b expression and adhesion in neutrophils exposed to reperfusion plasma only (CD11b expression fell from 15.9 to 3.4 mcf, p < 0.01 Mann-Whitney U-test and adhesion fell to 11.6% cells adhered, p < 0.01). CONCLUSION: An increase in CD11b expression is not required for an increase in neutrophil adhesion. The change in neutrophil adhesion produced by reperfusion plasma can be blocked by sICAM-1. Soluble ICAM-1 may have a physiological role in the regulation of neutrophil adhesion.

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Exercise-induced neutrophil activation in claudicants: a physiological or pathological response to exhaustive exercise?

OBJECTIVES: To assess the effect of exhaustive exercise on neutrophil activation and degranulation in claudicants and controls. We investigated the hypothesis that neutrophil activation and degranulation are normal responses to exhaustive exercise in healthy patients. DESIGN: This was a controlled experimental two-group study. MATERIALS: Exercise was performed using a fixed workload treadmill test. Neutrophil activation was assessed by flow cytometry of whole blood labelled with anti-CD11b mouse IgG, and neutrophil degranulation in terms of plasma elastase measured by enzyme-linked immunosorbent assay. METHODS: Twenty-eight claudicants with stage 1 chronic leg ischaemia, and 22 healthy controls were recruited. Blood and urine samples were collected before and after treadmill exercise. Claudicants exercised to their maximum walking distance, and controls at a higher "fatigue" workload for a maximum of 20 min. RESULTS: Exercise produced a brief but significant neutrophilia in both groups. Neutrophil CD11b expression increased significantly after exercise only in the claudicants, and was associated with a significant rise in plasma neutrophil elastase. These indices remained unchanged in the control group at all time points despite exercise at a fatigue level. CONCLUSION: The inflammatory response associated with exercise in claudicants is not simply a physiological response to exhaustive exercise.

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Percutaneous transluminal angioplasty for intermittent claudication: evidence on which to base the medicine.

OBJECTIVES: This study aims to assess the impact of PTA on the quality of life (QoL) of claudicants and to analyse which patients and which arterial lesions derive the most benefit. DESIGN: A prospective observational study. MATERIALS: One hundred and seventeen claudicants undergoing PTA were studied; 35 patients had bilateral disease, whilst 82 had unilateral disease and underwent PTA to a solitary iliac lesion, solitary superficial femoral or a iliac lesion above a diseased superficial femoral artery in 24, 39 and 19 cases, respectively. METHODS: Patients completed the Short Form 36 (SF36) and EuroQol (EQ) QoL assessment instruments prior to and at 1, 3, 6, and 12 months following intervention. The SF36 produces a QoL profile, whilst the EQ produces two QoL indices. RESULTS: Claudication has a deleterious effect on QoL, especially in patients with multi-segment disease. PTA results in an immediate and lasting improvement in the QoL of claudicants. Unilateral claudicants undergoing PTA to a solitary iliac lesion demonstrate the most marked QoL benefits and 12 months post PTA report a QoL approaching that of an age-matched population. Patients with bilateral claudication undergoing unilateral PTA and unilateral claudicants undergoing PTA to a solitary SFA lesion demonstrate some QoL benefits, but at 12 months post PTA do not approach the QoL scores of an age-matched population. Unilateral claudicants undergoing iliac PTA above a diseased SFA demonstrate minimal QoL changes. CONCLUSIONS: These results should influence decision making in the management of claudication and it may be possible to prioritise PTA waiting lists to ensure patients with greatest potential benefit are treated with most urgency.

Adult↗

Reduced total antioxidant capacity predicts ischaemia-reperfusion injury after femorodistal bypass.

BACKGROUND: Antioxidant defence systems are essential to protect the body from harmful free radicals released following ischaemia-reperfusion. The aim of this study was to examine the total antioxidant capacity (TAC) of patients with chronic critical leg ischaemia undergoing femorodistal bypass and to correlate this with lipid peroxidation, changes in capillary permeability and clinical outcome. METHODS: Twenty-five patients, 15 men and ten women of median age 71 (range 62-79) years, and 15 matched controls were studied. Blood was taken before operation and after reperfusion, with assays performed for malondialdehyde (a product of lipid peroxidation) and total antioxidant capacity. Changes in capillary permeability were measured by changes in the urinary albumin:creatinine ratio (ACR) following reperfusion of the ischaemic leg and expressed as a percentage increase from the preoperative value. Clinical outcome in terms of the systemic inflammatory response syndrome (SIRS) was recorded. RESULTS: Vascular patients who developed clinical evidence of a systemic inflammatory reaction following revascularization had a significantly reduced TAC compared with the controls (490 versus 860 mumol/l; P < 0.01, Mann-Whitney U test). These patients also demonstrated an increase in lipid peroxidation (0.5 versus 0.25 mumol/l, P < 0.05) and vascular permeability, as measured by the percentage increase in ACR (365 versus 130 per cent, P < 0.01). CONCLUSION: Vascular patients with a lower TAC developed increased capillary permeability as a result of ischaemia-reperfusion, which progressed to SIRS. TAC may provide a test to identify 'at risk' patients. It may be possible to augment their defence with exogenous antioxidants.

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Prospective analysis of quality of life in patients following infrainguinal reconstruction for chronic critical ischaemia.

BACKGROUND: The aims of this prospective study were to analyse the health-related quality of life (QOL) changes associated with infrainguinal arterial reconstruction for chronic critical limb ischaemia (CLI) and to assess the impact of graft patency and limb salvage. METHODS: Fifty-five consecutive patients, 28 women and 27 men of median age 71 (range 41-86) years, undergoing infrainguinal arterial reconstruction for CLI, consented to participate in the study. QOL was assessed using the Short Form 36 (SF36) health survey questionnaire, which was completed before and at 1, 3, 6 and 12 months following surgery. Graft patency was assessed by duplex imaging at the same postoperative intervals. RESULTS: CLI severely impaired QOL. Cumulative graft patency at 1, 3, 6 and 12 months after surgery was 82, 78, 76 and 64 per cent respectively. Reconstruction resulted in significant improvements in the SF36 domains Physical Functioning, Pain, Vitality and Social Functioning (P< 0.01). With a patent graft these improvements began soon after surgery and were maintained for the 12 months studied. Following irredeemable graft occlusion, patients who had secondary amputation also described some QOL improvements. CONCLUSION: A patent graft following infrainguinal arterial reconstruction for critical ischaemia results in an immediate and lasting improvement in health-related QOL.

Activities of Daily Living↗

Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis.

BACKGROUND: In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis. AIMS: To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with acute pancreatitis. METHODS: Glasgow score, Apache II, computed tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on admission in 34 patients with acute pancreatitis. Patients were stratified according to disease severity and randomised to receive either TPN or TEN for seven days and then re-evaluated. RESULTS: SIRS, sepsis, organ failure, and ITU stay, were globally improved in the enterally fed patients. The acute phase response and disease severity scores were significantly improved following enteral nutrition (CRP: 156 (117-222) to 84 (50-141), p < 0.005; APACHE II scores 8 (6-10) to 6 (4-8), p < 0.0001) without change in the CT scan scores. In parenterally fed patients these parameters did not change but there was an increase in EndoCAb antibody levels and a fall in TAC. Enterally fed patients showed no change in the level of EndoCAb antibodies and an increase in TAC. CONCLUSION: TEN moderates the acute phase response, and improves disease severity and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced systemic exposure to endotoxin and reduced oxidant stress also occurred in the TEN group. Enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial.

APACHE↗