ALK5 inhibition maintains islet endothelial cell survival but does not enhance islet graft revascularisation or function.

Islet transplantation is a potential treatment for Type 1 diabetes but long term graft function is suboptimal. The rich supply of intraislet endothelial cells diminishes rapidly after islet isolation and culture, which affects the revascularisation rate of islets after transplantation. The ALK5 pathway inhibits endothelial cell proliferation and thus inhibiting ALK5 is a potential target for improving endothelial cell survival. The aim of the study was to establish whether ALK5 inhibition prevents the loss of intraislet endothelial cells during islet culture and thus improves the functional survival of transplanted islets by enhancing their subsequent revascularisation after implantation. Islets were cultured for 48 h in the absence or presence of 2 different ALK inhibitors: SB-431542 or A-83-01. Their vascular density after culture was analysed using immunohistochemistry. Islets pre-cultured with the ALK5 inhibitors were implanted into streptozotocin-diabetic mice for either 3 or 7 days and blood glucose concentrations were monitored and vascular densities of the grafts were analysed. Islets cultured with ALK5 inhibitors had higher vascular densities than control-cultured islets. Three days after implantation, endothelial cell numbers in islet grafts were minimal, irrespective of treatment during culture. Seven days after implantation, endothelial cells were evident within the islet grafts but there was no difference between control-cultured islets and islets pre-treated with an ALK5 inhibitor. Blood glucose concentrations were no different between the treatment groups. In conclusion, inhibition of ALK5 improved intraislet endothelial cell numbers after islet culture, but this effect was lost in the early post-transplantation period.

Reducing the delay for carotid endarterectomy in South-East Scotland.

BACKGROUND AND PURPOSE: To establish whether the Scottish Intercollegiate Guidelines Network guidelines (SIGN 2008) publication has improved the delay from neurological event to carotid endarterectomy (CEA). This ideally should be performed within two weeks of a patient experiencing their first neurological event. METHODS: Data for 255 consecutive, symptomatic CEA procedures carried out under local anaesthetic, between March 2007 and June 2010 at The Edinburgh Vascular Surgery Service (EVSS) were extracted from the National Vascular Database. The mean, median and range was calculated for days from symptoms to vascular referral, vascular assessment to surgery and symptoms to surgery, subdivided according to four hospitals referring to the EVSS and whether CEA was performed pre- (n = 128) or post-publication of guidelines (n = 127). MAIN FINDINGS: Median delays from symptoms to vascular referral, vascular assessment to surgery and symptoms to surgery have decreased in all hospitals since the publication of the guidelines. The proportion of patients undergoing CEA within two weeks after their initial event increased from 25% pre-guidelines to 40.2% post-guidelines (p = 0.04). The proportion of patients undergoing CEA within four weeks of their event also improved from 57% to 74%. Patient presentation (41.8%), late referrals (29.9%) and lack of resources (22.4%) were the main causes for delay. CONCLUSIONS: Guidelines have improved service provision for CEA at the EVSS. However, more work is required to address the subgroup of patients whose surgery was delayed as a result of late presentation, late referral and lack of surgical resources.

Brachiobasilic fistula formation - single versus two stage procedure.

BACKGROUND: Brachial basilic (BB) fistulae are a form of vascular access for patients requiring dialysis. They are indicated when the cephalic vein is unsuitable for use. This fistula can be created with either a single stage or a two stage procedure. We aimed to compare the two techniques. METHODS: 73 BB fistulae (29 single and 44 two-stage) were created over a 5-year period (2003-2008). Data including sex, age, dialysis and diabetic status was collected from the case notes. Patency and time to maturity data was collected prospectively on an electronic database within the dialysis unit. RESULTS: There was no significant difference in functional patency rates between the two methods. A significant difference was identified between patients who had their fistula created prior to starting dialysis compared to those who had their fistula created after starting dialysis, in both initial patency rate (p = 0.017) and long term survival of the fistulae (p = 0.002). CONCLUSION: We identified no significant difference of patency between the two methods. This implies that a single stage procedure has benefits, by offering a quicker form of vascular access. Patients who had their fistulae created prior to dialysis had improved patency rates.

The radiological appearance of atherosclerotic popliteal artery aneurysms: the "dog-leg" sign.

The radiological appearance of popliteal aneurysms is described. Althought the lumen of the artery is often of normal diameter there is elongation of the vessel which frequently results in an acute "dog-leg". This sign has not been previously described.

The synthesis of novel 6,5- and 6,6-membered fused heterocyclic compounds derived from thymine.

Novel pyrimido[1,2-a]pyrimidinones 14, 15 and 16 and imidazo[1,2-a] pyrimidinones 19 and 20, designed as conformationally constrained analogues of 1-(3-amino-2-hydroxypropyl)thymine and 1-(2-amino-3-hydroxypropyl)thymine, respective ly, were synthesized by the ring-opening/ ring-closure rearrangement of the corresponding byciclic oxygen-containing amino compounds 12 and 17.

Cation exchange removal of Cd from aqueous solution by NiO.

Detailed adsorption experiments of Cd from aqueous solution on NiO were conducted under batch process with different concentrations of Cd, time and temperature of the suspension. The solution pH is found to play a decisive role in the metal ions precipitation, surface dissolution and adsorption of metal ions onto the NiO. Preliminary adsorption experiments show that the selectivity of NiO towards different divalent metal ions follows the trend Pb>Zn>Co>Cd, which is related to their first hydrolysis equilibrium constant. The exchange between the proton from the NiO surface and the metal from solution is responsible for the adsorption. The cation/exchange mechanism essentially remains the same for Pb, Zn, Co and Cd ions. The sorption of Cd on NiO particles is described by the modified Langmuir adsorption isotherms. The isosteric heat of adsorption (ΔH) indicates the endothermic nature of the cation exchange process. Spectroscopic analyses provide evidence that Cd is chemisorbed onto the surface of NiO.

Accuracy of the recording of operative events by the Scottish Morbidity Record 1 (SMR1) for a teaching hospital vascular unit.

OBJECTIVE: To determine the accuracy of operative data collected for the Scottish Morbidity Record 1 (SMR1). DESIGN: Retrospective comparative analysis of operative data recorded by the Scottish Office Information and Statistics Division (ISD) with that recorded in a locally held vascular database where the clinical information was entered by medical personnel. SUBJECTS: All patients with a codeable operative procedure carried out under the care of a single consultant vascular surgeon in a Regional Vascular Unit in 1994. RESULTS: A total of 840 admissions involving at least one OPCS4 code were recorded in the Vascular Database and 793 by the Scottish Office ISD. Although there was good agreement of the total number of operations and admissions, operative codes for 23 patients undergoing major abdominal aortic surgery and 19 undergoing major limb reconstruction were not recorded by the ISD. This represents 14% of total major arterial reconstructions in a single year. CONCLUSION: Accurate data collection has wide implications for research, monitoring future health trends, and planning hospital bed numbers. SMR1 data may accurately record total number of admissions and operations but is poor at distinguishing between those admissions that may be resource-intensive.

Mesenteric revascularisation for acute-on-chronic intestinal ischaemia.

Eleven patients (eight women) underwent urgent revascularisation for acute-on-chronic mesenteric ischaemia. Four patients had dual vessel and seven single vessel reconstructions. Two patients underwent simultaneous bowel resection and one patient has had three separate grafts to the superior mesenteric artery. There were two peri-operative deaths and three have died in the late follow-up period after 18, 24 and 36 months. The remainder have survived for between five and 63 months. Revascularisation for acute-on-chronic mesenteric ischaemia has been shown to be technically possible and of substantial benefit to patients who would otherwise be treated as terminal cases.

Management of iliac occlusions with a new self-expanding endovascular stent.

OBJECTIVES: To determine the patency and acceptability of the Memotherm endovascular stent in the treatment of iliac arterial occlusions. MATERIALS AND METHODS: Twenty-two patients (12 males and 10 females) underwent stenting of iliac occlusions of the aortoiliac bifurcation, the common iliac artery and the external iliac artery. All patients were reassessed at 3, 6 and 12 month intervals and then yearly to evaluate their symptoms and Doppler pressure measurements. Comparison was made with results from other studies treating iliac occlusions by angioplasty alone or combined with stenting. RESULTS: Out of 22 patients, 21 had an immediate and sustained improvement over the whole of the follow-up period. The Ankle-brachial Index (ABI) increased from a mean value of 0.49 to 0.81 3-months postprocedure and improved to 0.85 at 12 months (paired t-test p < 0.001). At 6 and 12 months the stent patency remained at 95.5%, which compares favourably with other studies. There were four minor and one major complication associated with the stenting procedure. CONCLUSIONS: The Memothern self-expanding stent is a useful, safe and effective device suitable for the majority of iliac occlusions. Further long-term evaluation is warranted to confirm its advantages over open surgery.

Aortic bifurcation reconstruction: use of the Memotherm self-expanding nitinol stent for stenoses and occlusions.

PURPOSE: To assess the technical success, initial clinical outcome, and intermediate follow-up of the Memotherm nitinol self-expanding stent in aortic bifurcation reconstruction. METHODS: Thirty-three patients (13 male, 20 female), mean age 64 years, were treated, who had symptoms classified by the Surgical Vascular Society/International Society of Cardiovascular Surgery (SVS/ICVS) classification as grade 2 in 11 (33%), grade 3 in 19 (58%) and grade 4 in 3 (9%) patients. Lesions were classified according to severity and type. Indications for placement of a Memotherm nitinol self-expanding stent were failed angioplasty in 14 (42%), chronic occlusions in 12 (37%), and complex stenoses in seven (21%) patients. RESULTS: Sixty-seven stents were technically successfully placed in 66 aorto-iliac segments in 33 patients, with one major complication. Initial clinical outcome was improvement in 25 (81%), no change in four (13%), and a worsening in two (6%) patients by Rutherford criteria. Mean early ankle/brachial pressure index (ABI) gain was 0. 27 for occlusions and 0.05 for stenoses. Clinical follow-up was obtained in all patients, with retrospective angiographic follow-up in 28 (85%) at a mean of 16 months (range 12-26 months). The decrease in ABI and the decrease in angiographic luminal diameter at follow-up was determined as the "late loss." The mean ABI late losses were -0.06, 0.00, and 0.09, and the mean angiographic late losses were 6.7%, 10% and 14% for occlusions, stenoses, and normal segments respectively. Primary clinical patency was 96%, primary angiographic patency was 89%, and secondary angiographic patency was 93%. CONCLUSION: The high technical success of stent placement, the low complication rates for aortic bifurcation reconstruction using the Memotherm self-expanding stent, and high clinical and angiographic patency maintained at intermediate follow-up support their use in aortic bifurcation reconstruction.

Disruption of skin perfusion following longitudinal groin incision for infrainguinal bypass surgery.

OBJECTIVE: The objective of our study was to investigate whether such an incision results in a reduction in blood flow, and therefore haemoglobin oxygen saturation, across the wound. DESIGN: Microvascular oxygenation was measured with lightguide spectrophotometry in 21 patients undergoing femoropopliteal or femorodistal bypass procedures. A series of measurements were made in the groin, medial and lateral to the surface marking of the femoral artery. The mean oxygen saturation on each side was calculated, and the contra-lateral groin was used as a control. The measurements were repeated at 2 and 7 days postop. RESULTS: Oxygen saturation in the skin of the operated groins was increased significantly from baseline at 2 days postop (f = 25.80, p < 0.001) and had begun to return to normal by day 7. The rise was more marked on the lateral side of the wound than on the medial (f = 12.32, p < 0.001). There was no such difference in the control groins. All wounds healed at 10 days. CONCLUSIONS: These results show a significant difference in skin oxygenation between the lateral and medial sides of the groin following longitudinal incision. This may contribute to the relatively high incidence of postoperative infection in these wounds.

Does immediate operation for symptomatic non-ruptured abdominal aortic aneurysm compromise outcome?

Background. The optimum timing of surgery for acutely symptomatic abdominal aortic aneurysm (AAA) remains a clinical dilemma: should symptomatic aneurysm be operated on urgently for fear of impending rupture, or should there be a period of preoperative evaluation to optimise the patient's medical co-morbidity, with a consequent delay in surgery? Method. Ninety-five patients were diagnosed with acutely symptomatic AAA (back pain, abdominal pain or a tender aneurysmal aorta) between 1995 and 2001 and included in a retrospective case-cohort study. The in-hospital mortality rates for patients undergoing early surgery (within 24h of presentation) were compared to those of patients whose surgery had been delayed to allow further evaluation. Results. Of 95 patients with an acutely symptomatic AAA, 70 had surgery within 24h of admission. The remaining 25 underwent planned delayed surgery after a median of (range) three (2-17) days. The reasons for delay to AAA repair were primarily to allow further cardiorespiratory assessment and radiological imaging. In the early surgery group, there were six postoperative deaths (9%); in the group who were to have delayed surgery, there were three (12%) deaths (P=0.694). Conclusion. Early operation for acutely symptomatic AAA, in selected patients, is not associated with an excessive mortality rate compared to delayed operation.