J. Vincent Smyth

The dinucleotide (CA) repeat polymorphism of estrogen receptor beta but not the dinucleotide (TA) repeat polymorphism of estrogen receptor alpha is associated with venous ulceration

Venous ulcers are the predominant form of chronic wound in the elderly, accounting for around 70% of all cases. The steroid sex hormone estrogen plays a crucial role in normal human skin maintenance and during cutaneous wound repair following injury. Estrogen can reverse age-related impaired wound healing by dampening the inflammatory response and increasing matrix deposition at the wound site. The molecular actions of estrogen are mediated through two nuclear sex steroid hormone receptors, estrogen receptor alpha (ERalpha) and beta (ERbeta). We have conducted a case-control study to investigate whether dinucleotide repeat polymorphisms in the estrogen receptor genes are associated with venous ulceration in the UK Caucasian population. Genomic fragments containing the ERalpha dinucleotide (TA)(n) repeat polymorphism or the ERbeta dinucleotide (CA)(n) repeat polymorphism were amplified by polymerase chain reaction in subject DNA samples and genotyped according to fragment length by capillary electrophoresis. There was no evidence to suggest that the TA repeat polymorphism of ERalpha was associated with venous ulceration. However, the CA*18 allele of the ERbeta CA repeat polymorphism was significantly associated with venous ulceration (n = 120, OR = 1.8, 95% CI = 1.1-2.8, P = 0.02). When the CA repeats alleles were grouped together into either low (L < or = 18) or high (H > 18) numbers of CA repeats, the low (L) repeat allele was significantly associated with venous ulceration (OR = 1.5, 95% CI = 1.0-2.2, P = 0.03). Our results show that a specific ERbeta variant is associated with impaired healing in the elderly, predisposing individuals to venous ulceration.

Systemic endotoxaemia and fibrinolysis during aortic surgery

OBJECTIVE To determine whether endotoxaemia and activation of the systemic fibrinolytic system occurs during and after aortic surgery. DESIGN Prospective clinical study. SETTING University Hospital. MATERIALS 31 patients undergoing aortic surgery. CHIEF OUTCOME MEASURES Venous blood assay for endotoxin and plasminogen activator inhibitor-1 (PAI-1). Samples were obtained preoperatively, immediately before and 5 minutes after cross-clamp application and removal, and at 2, 4, 6 and 24 hours postoperatively. Tonometric sigmoid intramural pH was monitored throughout this period as a means of detecting colonic mucosal ischaemia. MAIN RESULTS Endotoxin levels increased after clamping of the aorta, peaking immediately before clamp removal, mean value 34.5 pg/ml, p < 0.01, but returning to preoperative levels by 24 hours. PAI-1 levels progressively increased after surgery, with persistently high levels remaining at 24 hours (p < 0.01). CONCLUSIONS Endotoxaemia does occur during aortic surgery and appears to be associated with activation of the systemic fibrinolytic system.

The preservation of renal function by isovolemic hemodilution during aortic operations

PURPOSE In an investigation of the effects of isovolemic hemodilution, 39 consecutive patients undergoing elective infrarenal aortic operation had detailed measurements of renal function, renal artery blood flow, and cardiac hemodynamics. METHODS The patients were randomly allocated to receive acute preoperative isovolemic hemodilution to a hematocrit of 28%, with 20 patients receiving hemodilution and 19 being control subjects. RESULTS Twelve (63%) of the control group had renal impairment, compared with only four (20% in the group receiving hemodilution (p < 0.01). Hemodilution also prevented the fall in cardiac output induced by cross-clamping (p < 0.01) and significantly reduced the need for transfusion of donor blood (p < 0.01). CONCLUSIONS Acute isovolemic hemodilution is clearly a useful adjunct in the management of patients undergoing elective aortic operation.

Ruptured Infected Popliteal Artery Aneurysm

We describe an unusual presentation of an infected popliteal aneurysm. To our knowledge rupture of an aneurysm associated withSalmonellaat this site has not previously been reported. The management of infected aneurysms is discussed.

Evaluation of dopexamine hydrochloride as a renoprotective agent during aortic surgery

Thirty-two patients undergoing elective infrarenal aortic surgery were randomly assigned to receive a perioperative infusion of either dopexamine hydrochloride at a rate of 2 μg/kg/min (n = 15) or 0.9% saline solution as placebo (n = 17). Renal function was monitored by regular measurements of serum creatinine levels. There were significant mean percentage increases in serum creatinine (p < 0.001) at all time points up to 3 days postoperatively in the placebo group but only at 2 and 12 hours in the dopexamine group. It was concluded that dopexamine hydrochloride confers renal protection in patients undergoing aortic reconstruction.

Inflammatory Abdominal Aortic Aneurysms (IAAA): Past and Present

Aim: The aim of the study is to determine whether presentation and outcomes of inflammatory abdominal aortic aneurysms (IAAA) have changed over the last five decades. Methods: Comparison of current outcomes (January 2001 to December 2007) with results of the earliest report from our unit in 1972. Results: In contemporary series, 421 patients underwent AAA repair; 38 (9%) were IAAA. In 58% patients, IAAA was an incidental finding, whereas 42% patients were symptomatic with abdominal or back pain. Of those, 32% were ruptured IAAA. Male-to-female ratio was 12:1. Thirty-day mortality was 13%; elective 11.5%; emergency 17%. Comparison with 1972 study showed no change in the incidence and gender predilection. Presentation as an incidental finding and rupture increased 4- and 2-folds, respectively. Conclusion: The incidence and gender predilection of IAAA have remained unchanged. The 4-fold increase in the presentation as an incidental finding reflects current trends in patient evaluation.

Culture of human adult endothelial cells on endarterectomy surfaces

OBJECTIVES Endothelial cell seeding of prosthetic grafts has not been as successful as initially hoped and the application of seeding technology to alternative reconstructive procedures such as endarterectomy and angioplasty has been increasingly considered. The success of such seeding depends on the ability of the seeded cells to attach to, and form a monolayer on the endarterectomised vessel wall which was the aim of this study. METHODS Using a seeding chamber model, heterologous human adult endothelial cells were seeded onto fresh human endarterectomy specimens and cultured. Studies of endothelial call adherence to endarterectomy specimens were performed using 111-Indium oxine labelled cells using methodology analogous to graft seeding. RESULTS Mean endothelial cell adherence of 70% (S.D. 10%) after 1 h incubation was achieved and the successful development of a monolayer of human adult venous endothelial cells on endarterectomised arteries was demonstrated in vitro. CONCLUSIONS These results indicate that closed endarterectomy appears to offer a surface with cell attachment that is superior to prosthetic grafts. Where femoral endarterectomy is appropriate, endothelial seeding potentially offers a method of reducing thrombogenicity and intimal hyperplasia, improving patency and avoiding a prosthetic graft whilst preserving collateral circulation and autologous vein.

Production of plasminogen activator inhibitor-1 by human saphenous vein endothelial cells seeded onto endarterectomy surfaces in vitro

PURPOSE Endothelial cells produce many biologically important factors that may be used as functional markers, including plasminogen activators and their inhibitors (PAI). PAI-1 is a common peptide with a central role in the balance of thrombosis and fibrinolysis in vivo, and its production by vascular endothelial cells has been demonstrated for many in vitro cell lines. METHODS The basal rate of PAI-1 release from cultured human adult endothelial cells was studied in both a well-plate-seeding model and after seeding onto human endarterectomy specimens. The effect of nonspecific stimulation with thrombin on PAI-1 release was examined in well-plate cultures. PAI-1 was measured by enzyme-linked immunosorbent assay. RESULTS Cultured human saphenous endothelial cells release PAI-1 constitutively at a steady rate, which can be increased in the short term by the addition of thrombin. CONCLUSION After seeding onto endarterectomy specimens, seeded endothelial cells release significant amounts of PAI-1, which suggests that they retain functional integrity and may potentially influence thrombosis in vivo after seeding.

Endotoxemia: its relationship to colonic ischemia and aortic surgery. A preliminary report

Ten patients undergoing elective infrarenal aortic surgery were studied. Samples were taken perioperatively from a sigmoid tonometer to determine intramucosal pH (pHi) of the sigmoid colon, and simultaneously venous blood was taken for endotoxin measurement. Colonoscopy and biopsy were performed preoperatively and one week postoperatively. Significant endotoxemia was detected in 5 patients (50%), all of whom had transient colonic ischemia on the basis of tonometry, and of whom 2 had histologic evidence of ischemia at one week. Endotoxemia does occur during aortic surgery and appears to be associated with colonic ischemia, though this requires further evaluation.