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Biomedical subjects

R D Sayers

Publications and source records attributed to R D Sayers.

At least 19 recordsLinked to original sources
PubMed2003

Low atmospheric pressure is associated with rupture of abdominal aortic aneurysms.

INTRODUCTION: the rate of rupture of abdominal aortic aneurysms (AAAs) has been shown to have a seasonal variation with more ruptures occurring during the winter months. One of the main meterological changes between the seasons is a change in atmospheric pressure. The aim of this study was to investigate whether there was any relationship between atmospheric pressure and the incidence of AAA rupture. METHODS: all cases of ruptured AAA admitted to a single hospital over a ten year period were identified from hospital records. Daily atmospheric pressure readings from the nearest weather recording station to the hospital were obtained for the same period. Cases were only included if rupture could be confirmed by reviewing the patients case-notes. RESULTS: admission rates for ruptured AAA showed a monthly variation with the highest rate in December and the lowest in August. There was a statistically significant correlation between the number of cases admitted in any particular month and the mean atmospheric pressure for the previous month. Neither daily minimum, maximum or mean pressure, weekly mean pressure or daily pressure variability were significantly different between those days when a ruptured AAA was admitted and those when no ruptured AAA was admitted. CONCLUSIONS: low atmospheric pressure is associated with increased rate of AAA rupture. The method by which this change in pressure precipitates rupture cannot be determined from this study.

Aortic Aneurysm, Abdominal↗
PubMed2003

The role of cytokine gene polymorphisms in the pathogenesis of abdominal aortic aneurysms: a case-control study.

BACKGROUND: Cytokines are the primary mediators of inflammation and also influence matrix metalloproteinase expression, both of which are important in development of abdominal aortic aneurysm (AAA). A significant, but as yet unknown, familial factor contributes to the pathogenesis of AAA. Many cytokine genes contain polymorphic sites, some of which affect cytokine production in vitro. Cytokine gene polymorphisms may therefore influence the pathogenesis of AAA. The purpose of this study was to determine whether there is any association between cytokine gene polymorphisms and AAA. METHODS AND RESULTS: This case-control study comprised 100 patients with AAA and 100 age-matched and sex-matched control subjects. For each case and control subject in the study, genotypes at the following cytokine gene polymorphic loci were determined: interleukin (IL)-1beta +3953, IL-6 -174, IL-10 -1082, IL-10 -592, and tumor necrosis factors-alpha -308. Allele and genotype frequencies were compared between AAA and control groups, and odds ratios (OR) were calculated for the presence of AAA with each allele at each locus examined as risk factors. The IL-10 -1082 A allele was significantly more common in the AAA group than the control group (P =.03). The OR for the IL-10 -1082 A allele as a risk factor for AAA was 1.8 (95% confidence interval, 0.9-3.6). DISCUSSION: These associations suggest a significant role for IL-10 in the pathogenesis of AAA. This association of AAA with the IL-10 -1082 A allele is also biologically plausible; the IL-10 -1082 A allele is associated with low IL-10 secretion, and it may be that AAA develops in patients who are unable to mount the same anti-inflammatory response as those who do not have AAA.

Aged↗
PubMed2003

The systemic inflammatory response syndrome, organ failure, and mortality after abdominal aortic aneurysm repair.

BACKGROUND: Organ failure is a major cause of morbidity and mortality after abdominal aortic aneurysm (AAA) repair. The aim of this study was to determine the relationships between the systemic inflammatory response syndrome (SIRS), organ failure, and mortality after AAA repair and to determine whether the clinical monitoring of SIRS was a useful adjunct to clinical method. METHODS: One hundred consecutive patients undergoing open AAA repair were prospectively studied. Patients were divided into three groups: those undergoing elective AAA repair, those with symptomatic but nonruptured AAA, and those with ruptured AAA. The presence of SIRS and organ failure was recorded on a daily basis for each patient until discharge or death. RESULTS: Most patients had SIRS develop during the postoperative period: 89% of the elective group, 92% of the emergency nonruptured (urgent) group, and 100% of the ruptured group. Multiorgan failure occurred in 3.8% of the elective group, 38% of the urgent group, and 64% of the ruptured AAA group. After ruptured AAA repair, the concurrent absence of both SIRS and any organ failure for 48 hours had a sensitivity of 93% and a specificity of 91% as a predictive indicator of subsequent survival to hospital discharge. Patients in whom multiorgan failure developed after ruptured AAA repair had a significantly higher mortality rate (69%) than those who did not (0%; P =.001; 95% CI for the difference, 30.2% to 85.8%). CONCLUSION: The differences in the incidence rate of multiorgan failure between the patient groups compared with the high incidence rate of SIRS in all patient groups supports the two-hit hypothesis of multiorgan failure. The presence of multiorgan failure after ruptured AAA repair is associated with poor outcome. The absence of SIRS and organ failure in these patients is a good predictive indicator of survival.

Aged↗
PubMed2002

A meta-analysis of 50 years of ruptured abdominal aortic aneurysm repair.

BACKGROUND: Operative repair of ruptured abdominal aortic aneurysm (RAAA) is associated with a high mortality rate but reported figures vary widely. The aim of this study was to estimate the operative mortality of RAAA repair and determine how it has changed over time. METHODS: A meta-analysis of all English language literature quoting figures for operative mortality of RAAA repair. RESULTS: The pooled estimate for the overall operative mortality rate of RAAA repair from 1955 to 1998 was 48 (95 per cent confidence interval 46 to 50) per cent. Meta-regression analysis of operative mortality over time demonstrated a constant reduction of approximately 3.5 per cent per decade (1954-1997) with an operative mortality rate estimate for the year 2000 of 41 per cent. Seventy-seven studies reported intraoperative mortality but, while this appears to have remained constant over time, there was evidence of the presence of publication bias in the subgroup of papers reporting this outcome. There was no evidence of publication bias for the overall operative mortality outcome. CONCLUSION: Contrary to the conclusion of recent studies, this paper demonstrates a gradual reduction with time in the operative mortality rate of RAAA repair.

Aged↗
PubMed2002

Prosthetic patch infection after carotid endarterectomy.

OBJECTIVES AND DESIGN: prospective audit of the management and outcome of prosthetic patch infection after carotid endarterectomy (CEA) at Leicester Royal Infirmary plus review of the literature. RESULTS: 8/936 CEA patients (0.85%) developed a prosthetic patch infection. Responsible organisms included MRSA (n=3), Staphylococcus epidermidis(n=2), haemolytic Streptococcus (n=1), Staphylococcus aureus(n=1) and Pseudomonas (n=1). Early wound complications preceded 4/5 infections presenting within 9 weeks of surgery. In addition to systemic antibiotics and debridement, management included patch removal and: (i) carotid ligation (n=3), vein patch repair (n=1), vein bypass (n=3). One patient had antibiotic irrigation of the in-situpatch. No patient died, one suffered a disabling postoperative stroke and two had temporary cranial nerve injuries. Including this series, a literature review identified 43 prosthetic patch infections, 91% culturing Staphylococci or Streptococci. Cumulative freedom from perioperative stroke/death or re-infection was 65% at 2 years. Patients treated by patch excision and autologous venous reconstruction had the best outcome with a cumulative freedom from perioperative stroke/death or re-infection of 91% at 2 years. CONCLUSION: prosthetic patch infection after CEA is rare. This study emphasises the importance of close surveillance of early wound complications. Surgical decision-making, especially the safety of carotid ligation, was facilitated by access to transcranial Doppler.

Bacterial Infections↗
PubMed2002

An aggressive policy of bilateral saphenous vein harvest for infragenicular revascularisation in the era of multidrug resistant bacteria.

BACKGROUND: The success of infragenicular revascularisation for lower limb ischaemia is limited by the high proportion of patients without ipsilateral long saphenous vein (LSV) of adequate length or quality. The aim of this study was to report the results of an autogenous vein only policy for infragenicular revascularisation utilising contralateral LSV when ipsilateral LSV is inadequate. The treatment and outcome of infection of autogenous grafts with methicillin resistant Staphylococcus aureus (MRSA) is also reported. PATIENTS AND METHODS: The vascular audit database and patient case notes were reviewed retrospectively for patients with arterial occlusive disease requiring infragenicular reconstruction. There were 68 critically ischaemic legs in 65 patients of whom 48 were male: median age (range) 74 years (41-94), over a three year period. RESULTS: Thirty six patients (53%) underwent revascularisation (eight infragenicular femoropopliteal bypass, 28 femorodistal), 24 (35%) underwent primary amputation and a further eight (12%) were found to have unsuitable distal vessels for revascularisation after tibial vessel exploration and intraoperative angiography. Thirty three grafts (92%) utilised LSV and three (8%) were polytetrafluoroethylene grafts. Thirteen patients (39%) lacked adequate ipsilateral LSV of whom 12 had the contralateral leg explored providing suitable LSV in 10/12 (83%). Contralateral LSV was used as a single length conduit in two cases and as a venovenous composite graft in eight cases. Primary, primary assisted, and secondary patency rates at two years were 38%, 77%, and 81% respectively. Actuarial limb survival and patient survival rates at two years were 86% and 61% respectively. Eleven patients developed ipsilateral wound complications (30%) including seven (21%) who developed MRSA infection of the ipsilateral leg wound. MRSA wound infection was treated successfully in all cases by antibiotic therapy (intravenous vancomycin). No patient subsequently required saphenous vein harvesting for a secondary reconstruction or coronary artery bypass graft. CONCLUSION: Excellent long term results can be achieved using autogenous vein for infragenicular revascularisation and the contralateral LSV is an excellent alternative in the absence of suitable ipsilateral LSV. Autogenous vein may confer some protection against severe complications observed with MRSA infection seen in vascular patients and therefore its use is recommended.

Adult↗
PubMed2002

Aortic aneurysms, inflammatory pathways and nitric oxide.

The Leicester experience of treatment of aortic aneurysms indicates that workload is increasing. Despite an increase in elective repairs, the number of ruptured abdominal aortic aneurysms is also increasing. The mortality of ruptured abdominal aortic aneurysm remains static despite advances in critical care medicine. Multi-organ failure is the commonest cause of death following ruptured abdominal aortic aneurysm and the systemic inflammatory response syndrome, ischaemia-reperfusion injury and activation of inflammatory pathways are important precursors. Organ failure, reperfusion injury and inflammatory pathway activation can be studied at a cellular and biochemical level in animal models of aortic cross-clamping. The nitric oxide response is an important component of the inflammatory response and augmentation of the NO response may protect against renal injury caused by aortic cross-clamping during aortic aneurysm repair.

Aortic Aneurysm, Abdominal↗
PubMed2001

Cytokines and inflammatory pathways in the pathogenesis of multiple organ failure following abdominal aortic aneurysm repair.

Multiple organ failure is a common mode of death following abdominal aortic aneurysm repair, particularly after rupture. Cytokines are the principal mediators of the inflammatory response to injury and high levels of circulating cytokines have been associated with poor outcome in major trauma and sepsis. Abdominal aortic aneurysm repair results in an ischaemia-reperfusion injury to the tissues distal to the site of aortic clamping. The inflammatory response in these tissues causes the release of cytokines, principally Interleukins 1-beta, 6, and 8, and Tumour Necrosis Factor alpha. If released in large enough concentrations, these cytokines may enter the circulation and gain access to organs distant to the site of initial injury. Circulating cytokines cause dysfunction of the renal, cardiovascular, respiratory, nervous and musculo-skeletal systems. The combination of these individual changes in organ function is the multiple-organ dysfunction syndrome, which may progress to multiple organ failure.

Aortic Aneurysm, Abdominal↗
PubMed2001

Methicillin-resistant Staphylococcus aureus infection in vascular surgical patients.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is emerging as a major problem in vascular surgical practice. The aim of this study was to review the management of patients with MRSA infection complicating vascular surgical operations. METHODS: Data were obtained from the vascular audit, case notes, intensive therapy unit (ITU) notes, high dependency unit (HDU) notes and microbiological records of patients who underwent either arterial reconstruction (n = 464) or limb amputation (n = 110) between April 1994 and October 1998. RESULTS: Forty-nine vascular surgical patients developed clinical MRSA infection (9%). Clinical MRSA infection in patients who had undergone aorto-iliac reconstruction (n = 18) was associated with a 56% mortality (n = 10) and the most common infections were bacteraemia (55%) and pneumonia (50%). MRSA infection occurred in 17 patients who had undergone infra-inguinal bypass and was associated with a 29% mortality (n = 5). The most common site of MRSA infection was the groin wound (76%) leading to anastomotic dehiscence and death in one patient (11%) and necessitating wound debridement in 4 patients (22%). MRSA infection of the groin wound in the presence of a prosthetic graft (n = 3) led to anastomotic dehiscence in 2 patients, and graft excision in 2 patients. Similar complications were not observed in the presence of an underlying autogeneous long saphenous vein graft (n = 16). MRSA infection following major lower limb amputation (n = 14) was associated with death in 5 patients (36%). Wound infection in 10 amputees (71%) led to revision of the amputation to a higher level in 2 (14%) and wound debridement in 2 (14%). CONCLUSIONS: MRSA infection has a high mortality in vascular surgical patients in general, and following aorto-iliac reconstruction in particular. Autogeneous vein may confer some protection against local complications following groin wound infection. Strategies aimed at reducing the incidence of infection, including strict adherence to infection control procedures, may reduce the severity of this problem.

Adolescent↗
PubMed2000

Pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury.

OBJECTIVES: to investigate endogenous pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury. METHODS: groups of male Wistar rats (n=6) were subjected to 60 minutes of infrarenal aortic cross-clamping under general anaesthesia. Rats were culled after 0, 60 and 120 minutes>> reperfusion, following release of the aortic clamp. A sham-operated control group was also studied. Acute lung injury (ALI) was quantified by measuring the protein concentration in lung bronchoalveolar lavage (BAL) fluid. Pulmonary myeloperoxidase activity (MPO) was measured as an index of neutrophil infiltration and degranulation in the lung. Plasma tumour-necrosis factor-alpha (TNF-alpha) was measured as an index of the pro-inflammatory cytokine response and pulmonary nitric oxide synthase (NOS) activity was determined by measuring conversion of(3)H L-arginine to(3)H L-citrulline in tissue homogenates. RESULTS: these data show significant ALI with increased pulmonary microvascular permeability and MPO activity in animals subject to 60 minutes>> ischaemia and 60 minutes or 120 minutes of reperfusion compared to control animals (p<0.01). Plasma TNF-alpha levels were significantly increased following 60 minutes of ischaemia compared to controls (p<0.01) and remained significantly increased in animals subject to reperfusion (p<0.01). Pulmonary NOS activity was significantly increased in animals subject to reperfusion (p<0.01). CONCLUSIONS: the reperfusion phase of infrarenal aortic cross-clamping provokes a significant increase in pulmonary NOS metabolism. The increase in plasma TNF-alpha and MPO activity suggests that this response may be secondary to inducible NOS expression. Manipulation of this response may benefit patients at risk of acute injury following infrarenal aortic reconstruction.

Animals↗
PubMed2000

Prevention of renal impairment following aortic cross-clamping by manipulation of the endogenous renal nitric oxide response.

OBJECTIVE: Infrarenal aortic cross-clamp-induced lower torso ischaemia-reperfusion injury is associated with impairment of glomerular filtration rate and upregulation of endogenous renal nitric oxide production. The aim of this study was to investigate whether manipulation of the endogenous renal nitric oxide response can ameliorate subsequent renal injury. METHODS: Groups of male Wistar rats (n = 6) were treated with one of the following agents before being subjected to 60 min of infrarenal aortic cross-clamping: saline (control), L-NMMA (a pan nitric oxide synthase inhibitor), 1400W (a highly selective iNOS inhibitor), hydrocortisone (an inhibitor of the systemic inflammatory response), L-arginine (the substrate for nitric oxide synthase) and NOC-18 (a nitric oxide donor). Animals were recovered after a left nephrectomy. The glomerular filtration rate (GFR) of the remaining kidney was measured on the second and seventh postoperative day using a 99Tc DPTA clearance technique as an index of renal injury. RESULTS: Animals treated with L-NMMA prior to aortic cross-clamping had a significantly impaired GFR compared to controls on the second (p<0. 01, Mann-Whitney U -test) and seventh (p<0.05, Mann-Whitney U -test) postoperative day. Hydrocortisone and 1400W had no significant effect on GFR on the second or seventh postoperative day. L-arginine and NOC-18 had no influence on GFR on the second postoperative day but significantly improved GFR on the seventh postoperative day. CONCLUSIONS: These results show that the endogenous nitric oxide response protects the kidneys from ischaemia-reperfusion injury. Manipulation of the renal nitric oxide response may have therapeutic benefits to patients undergoing aortic aneurysm repair by preventing acute renal failure.

Animals↗
PubMed2000

Outcome of acute renal failure following surgical repair of ruptured abdominal aortic aneurysms.

OBJECTIVES: to establish the mortality of ARF following surgical repair of ruptured abdominal aortic aneurysms (AAAs) and to identify clinical variables which might assist in predicting outcome. DESIGN, MATERIALS AND METHODS: all cases of ARF complicating repair of ruptured AAAs treated at Leicester General Hospital between 1984 and 1996 were identified in a retrospective study based on review of clinical records. The main outcome measures were overall mortality, duration of hospital treatment and renal function in survivors. RESULTS: in 65 cases identified, overall hospital mortality was 75%. Six patients did not receive RRT, since their clinical state was judged irreversible; all died. Of the 16 survivors, 11 were left with irreversible renal impairment and one patient required maintenance dialysis. Over half of the survivors had died at 5 years>> follow-up. Non-survivors had more vascular disease (p=0.048), required more surgery during AAA repair (p=0.042) and were more likely to have developed multiple organ failure (p=0.01). A clinical severity score based on these three variables allowed stratification into prognostic groups. CONCLUSIONS: ARF following surgical repair of ruptured AAA has an overall hospital mortality of 75%. A clinical severity score, calculated at the time dialysis was considered, may assist in prediction of outcome.

APACHE↗
PubMed1999

In situ replacement of infected aortic grafts with rifampicin-bonded prostheses: the Leicester experience (1992 to 1998)

PURPOSE: Prosthetic graft infection after aortic aneurysm surgery is a life-threatening complication. Treatment options include total graft excision and extra-anatomic bypass grafting or in situ replacement of the graft. The latter option is gaining increasing popularity, but the long-term outcome remains uncertain, particularly in light of the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA). We performed a prospective nonrandomized study to assess the outcome after graft excision and in situ replacement with a rifampicin-bonded prosthesis for the treatment of major aortic graft infection. METHODS: In a 6-year period from January 1992 to December 1997, 11 patients (eight men, three women) with major aortic graft infection underwent total graft excision and in situ replacement with a rifampicin-bonded prosthesis. The median age of the patients was 66 years (range, 49 to 78 years). Four patients had a hemorrhage from an aortoenteric fistula, three had a retroperitoneal abscess, two had graft occlusion, one had a perigraft collection shown by means of computed tomography, and one had a ruptured suprarenal false aneurysm. Organisms were cultured from 10 patients. RESULTS: MRSA was isolated in two patients, both of whom had originally undergone repair of a ruptured abdominal aortic aneurysm. Two patients died (18.2%) within 30 days, and three patients (27.6%) had nonfatal complications (peritoneal candidiasis, transient renal impairment, and profound anorexia). Two patients died late in the follow-up period. Seven patients remain alive and clinically free of infection. CONCLUSION: The long-term results after total graft excision and in situ replacement with a rifampicin-bonded prosthesis appear to be favorable. However, MRSA aortic graft infection appears to be associated with a poor prognosis.

Aged↗
PubMed1999

Endogenous renal nitric oxide metabolism following experimental infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury.

BACKGROUND: Abdominal aortic surgery is associated with marked changes in renal haemodynamics. The aim of this study was to investigate the influence of infrarenal cross-clamping on glomerular filtration rate and endogenous renal nitric oxide metabolism. METHODS: Groups of male Wistar rats were subjected to infrarenal aortic cross-clamping followed by reperfusion. Animals were allowed to recover after a left nephrectomy. The glomerular filtration rate of the remaining kidney was measured on the second and seventh day after the procedure before the animal was killed and the remaining kidney harvested. Total nitric oxide synthase (NOS) activity and expression of inducible NOS (iNOS) was determined in renal tissue following 1 h and 7 days of reperfusion. RESULTS: Glomerular filtration rate was impaired on the second and seventh day after operation in all animals subjected to lower torso ischaemia compared with controls (P < 0.05). Renal NOS activity was increased at 1 h and 7 days in animals subjected to infrarenal cross-clamping compared to controls (P < 0.01). iNOS was detected in renal tissue of animals subjected to infrarenal aortic cross-clamping on the seventh day after operation. CONCLUSION: Infrarenal aortic cross-clamping is associated with impairment of renal function in the early postoperative period. There is an increase in endogenous renal nitric oxide metabolism with iNOS expression. Presented in part to the Surgical Research Society, Dublin, Ireland, July 1998

Animals↗
PubMed1999

Non-cardiogenic pulmonary oedema in vascular surgery.

Non-cardiogenic pulmonary oedema, an early manifestation of the adult respiratory disease syndrome, is a serious complication following major vascular surgery. Hypovolaemia, ischaemia-reperfusion injury, massive blood transfusion, transient sepsis and transient endotoxaemia are insults responsible for initiating the process in vascular surgical patients. Free radicals, cytokines and humoral factors released secondary to the above insults activate neutrophils and facilitate their interaction with the endothelium. Activated neutrophils marginate through the endothelium where they are responsible for tissue injury by the release of free-radicals and proteases. The lungs are a large reservoir of neutrophils and bear a significant part of the injury. Conventional therapy includes treating the underlying condition and providing respiratory support. A better understanding of the pathophysiology of this process has led to new experimental treatment options. Novel therapeutic interventions have included the use of compounds to scavenge free radicals, anti-cytokine antibodies, extracorporeal lung support, nitric oxide and artificial surfactant therapy. The multifactorial nature of this process makes it unlikely that a single "magic bullet" will solve this problem. It is more likely that a combination of preventative, prophylactic and therapeutic modalities may reduce the mortality of this condition.

Humans↗