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Biomedical subjects

J S Budd

Publications and source records attributed to J S Budd.

At least 37 records · Page 2Linked to original sources

Selection of patients with critical limb ischaemia for femorodistal vein bypass.

The merits of an aggressive policy of distal reconstruction have been questioned by some observers. To determine the factors affecting graft patency and mortality, we analysed 78 consecutive infragenicular femorodistal vein grafts performed in 72 patients with critical limb ischaemia. The primary, primary assisted and secondary graft patency rates at 36 months were 29, 57 and 64%, respectively. The limb salvage and patient survival rates at 36 months were 67 and 74%, respectively. Univariate analysis (log-rank test) was performed to identify factors affecting graft patency, limb salvage and mortality at 1 month (perioperative) and 1 year. Independent variables of age, sex, diabetes, presentation, level of anastomosis and vein technique (reversed or in situ) did not affect graft patency. The ankle systolic pressure did not predict graft patency but was an independent variable affecting mortality (p = 0.047), as did diabetes (p = 0.019). These results show that excellent limb salvage can be successfully achieved in severely ischaemic patients by adopting an aggressive approach to femorodistal bypass, and that age, gender and poor medical condition are not contraindications to femorodistal bypass. The difference between the primary and primary assisted patency rates in this series is dramatic and reflects the impact of a vein graft surveillance programme in preventing graft occlusion.

Adult↗

A method to transluminally seed angioplasty sites with endothelial cells using a double balloon catheter.

Acute arterial reocclusion and late restenosis following angioplasty may be partially caused by loss of the endothelial cell monolayer during balloon dilatation. Rapid restoration of the endothelial cell monolayer by endothelial cell transplantation has the potential to increase the antithrombotic nature of the angioplasty site and also to prevent myointimal hyperplasia which is the cause of late restenosis. We have investigated a method to transluminally deliver endothelial cells to angioplasty sites using a double balloon catheter with a central instillation port. Inflation of the balloons allows a segment of artery to be isolated from the circulation which may then be incubated with infused endothelial cells. The external iliac arteries of New Zealand white rabbits were dilated for 30 s at 8 atm pressure using a 3 mm balloon angioplasty catheter. Indium-111 labelled allogeneic rabbit endothelial cells were seeded onto the angioplasty site and retained in contact with the vascular surface for 30 min by continued inflation of the isolation balloons. After 30 min, the balloons were deflated and flow restored. Percentage cell retention was calculated by determining the gamma activity of the seeded angioplasty site, and referencing this to the contralateral sham seeded site. Results are expressed as a median with 95% confidence intervals and suggest that endothelial cells may be successfully delivered and retained on damaged vascular surfaces [table: see text].

Angioplasty, Balloon↗

The effectiveness of low dose slow release aspirin as an antiplatelet agent.

An open, randomized, parallel group study of three different aspirin preparations was carried out. The objective of this study was to compare their ability to inhibit the production of thromboxane A2 (measured as thromboxane B2 [TXB2]) from platelets. Three aspirin preparations were studied: Acetard 300 mg, Acetard 100 mg and Platet 100 mg. The study was conducted in 45 healthy adult volunteers and treatment continued once daily for 7 days. The results of the TXB2 assay show that the administration of all three treatment preparations produced a rapid drop in TXB2 levels of all volunteers. The baseline TXB2 level was reduced by 95% for all groups by day 3. Analysis by day showed a significant difference (P < 0.05) between treatments at day 1, with Acetard 100 mg having higher TXB2 levels than the other two groups. Analysis of changes from baseline showed a significant reduction (P < 0.05) in TXB2 levels at Days 1 to 14 for all three groups. Platelet aggregation also showed a significant reduction, being reduced to 10% of control at 7 days. It then reverted back to baseline by 28 days for all treatment groups. In conclusion, low dose aspirin is very effective as an antiplatelet agent and in a slow release form loses none of its patency.

Adult↗

Prostacyclin production from seeded prosthetic vascular grafts.

Endothelial cell seeding has been proposed as a method of improving patency rates in small-calibre prosthetic vascular grafts. In vivo, endothelial cells normally produce prostacyclin (PGI2), a potent antiplatelet agent. The aim of this study was to determine whether seeded grafts show significant PGI2 production after in vivo implantation. Grafts were seeded with either autologous canine venous endothelial cells or autologous microvascular endothelial cells. After 12 weeks, PGI2 production was assessed under basal and stimulated conditions. Seeded grafts were compared with non-seeded controls and the corresponding aorta. The overall patency rate in seeded grafts was 80 per cent compared with 10 per cent in non-seeded grafts (P < 0.01). Grafts seeded with cells from either source produced significantly more PGI2 than unseeded grafts in both basal and stimulated states (P < 0.05). The aorta produced significantly more PGI2 than seeded grafts under both conditions (P < 0.01). Endothelial cell seeding produces a functional graft and leads to an improved patency rate.

Animals↗

Endothelial cell seeding of damaged native vascular surfaces: prostacyclin production.

Endothelial cell seeding has been successful in reducing the thrombogenicity of prosthetic vascular grafts in animal and clinical studies. The reduction in thrombogenicity may be attributed to the intrinsic properties of endothelial cells themselves, and their ability to produce anti-thrombogenic mediators such as prostacyclin, and endothelium-derived relaxing factor. Endothelial seeding of damaged vascular surfaces produced during percutaneous transluminal angioplasty and endarterectomy is an attractive possibility due to the excellent attachment characteristics of the sub-endothelial tissue exposed during these procedures. The ability of endothelial seeded damaged vascular surfaces to produce prostacyclin was measured in an in vitro model of vascular injury. Endothelial-seeded damaged surfaces produced significantly higher prostacyclin release than did vessels damaged by balloon dilatation (265.5 pg cm-2 min-1 and 87.5 pg cm-2 min-1 respectively). This study provides evidence that endothelial seeding of damaged native vascular surfaces is technically feasible and that seeding may reduce the thrombogenicity of vascular surfaces following balloon dilatation.

Angioplasty, Balloon↗

Therapeutic options in subclavian artery disease.

Chronic ischaemia of the upper limb secondary to subclavian artery disease is uncommon. These patients may present with a variety of symptoms caused by cerebrovascular or upper limb hypoperfusion. If these symptoms are severe, revascularization may be required. This may be accomplished by percutaneous transluminal angioplasty or surgery. The experience of the management of these patients has been reviewed to document their presentation, treatment and outcome.

Adult↗

Effects of two methods of endothelial cell seeding on cell retention during blood flow.

The potential benefits of endothelial cell seeding depend not only on effective cell attachment, but also on the ability of the cells to resist the stresses of blood flow. We have investigated the effect of different blood flow rates on immediately seeded grafts (SHORT) and also on preformed confluent monolayers formed by overnight incubation (LONG). Cells were labelled with indium and then exposed to either 100 or 200 ml/min of pulsatile blood flow. Cell retention was measured up to 120 min. At both flow rates the LONG seeding procedure gave significantly better cell retention than the SHORT method (P less than 0.01 at all times). There was no difference in cell retention between the two flow rates in the LONG group, but more cells detached at the higher flow rate in the SHORT group (P less than 0.01). We conclude that the new seeding method, using preformed confluent monolayers, significantly improves cell retention during blood flow.

Blood Flow Velocity↗

Above-knee prosthetic grafts do not compromise the ipsilateral long saphenous vein.

Prosthetic graft materials are used preferentially by a number of surgeons for above-knee femoropopliteal bypasses. Using B-mode ultrasonography we have assessed the ipsilateral long saphenous vein in patients undergoing such bypasses to determine its suitability for future use in more distal bypasses. A total of 137 above-knee prosthetic grafts were performed over a 10-year period. Of the patients, 74 were available for further assessment. Overall, 97 per cent of veins were suitable for future bypass surgery if required. Above-knee prosthetic bypasses do not appear to jeopardize the ipsilateral long saphenous vein.

Arteriovenous Shunt, Surgical↗

The effect of preformed confluent endothelial cell monolayers on the patency and thrombogenicity of small calibre vascular grafts.

Endothelial cell seeding has been proposed as a method to improve the patency rates in small calibre prosthetic vascular grafts. The seeding methods used at present leave much of the graft luminal surface devoid of endothelial cells and thus still significantly thrombogenic. We have developed a method to preform confluent endothelial cell monolayers, on the grafts prior to implantation, and this study investigates the effect of these monolayers on the early thrombogenicity and patency of polytetrafluoroethylene (PTFE) grafts. Small diameter PTFE grafts were seeded with canine endothelial cells obtained from the external jugular vein. Each of five dogs then received a graft seeded with its own cells and a contralateral, non-seeded control graft. At 1 and 10 weeks after graft implantation graft thrombogenicity was assessed by the use of Indium labelled platelets. The thrombogenicity index (TI) of each graft was determined from counts of gamma activity recorded over a period of 7 days. Grafts were subsequently removed at 12 weeks. At 1 week the mean TI for the seeded grafts was 0.123 (SD 0.019) and that for the controls 0.183 (SD 0.017) (p = 0.005). At 10 weeks only the seeded grafts could be assessed because all of the control grafts had occluded. At this point in time the seeded grafts had a mean TI of 0.159 (SD 0.011) (p = 0.047 vs. seeded at 1 week). By the time of removal at 12 weeks, all control grafts were occluded but only one of the seeded grafts had occluded (p = 0.025). In conclusion, the use of preformed, confluent endothelial cell monolayers for seeding prosthetic grafts significantly reduces the early graft thrombogenicity and improves graft patency. It does not, however, completely halt the increase in thrombogenicity which occurs during the early post-implantation period.

Animals↗

Infrainguinal bypass surgery: factors determining late graft patency.

The results of 373 infrainguinal bypass grafts, in a single centre, between 1980 and 1988 are reviewed. One hundred and thirty in situ vein (ISV), 47 reversed saphenous vein (RSV), 118 polytetrafluoroethylene (PTFE) and 78 human umbilical vein (HUV) grafts were used. The indications for surgery were disabling claudication in 25 per cent of patients and limb salvage in 75 per cent. In 36 per cent of operations the distal anastomosis was above the knee and in 64 per cent it was below the knee. Overall 5-year patency rates and limb salvage rates respectively were, for ISV (41 and 69 per cent), RSV (62 and 90 per cent), PTFE (31 and 67 per cent) and HUV (29 and 59 per cent). There was no significant difference in patency among these grafts at the above-knee level, but significant differences between vein and prosthetic grafts were evident below the knee (P less than 0.001). Using a proportional hazards model the three factors that consistently correlated with late graft patency were graft type (P less than 0.001), site of distal anastomosis (P less than 0.001) and distal run-off (P less than 0.001). Overall, the results suggest that prosthetic grafts are a suitable alternative to autogenous vein when the distal anastomosis is above the knee, but vein should always be used, if available, below the knee joint.

Adult↗

The effect of varying fibronectin concentration on the attachment of endothelial cells to polytetrafluoroethylene vascular grafts.

Endothelial cell seeding onto untreated polytetrafluoroethylene vascular prostheses is inefficient. In an effort to improve cell attachment, numerous investigators have used fibronectin as a coating material to pretreat the luminal surfaces of these prostheses. The concentrations of fibronectin used have varied enormously, and no one has yet determined the most efficient concentration in terms of cell attachment and cost. Using endothelial cells labeled with indium 111 oxine we have studied the effect of varying fibronectin concentration on the attachment of these cells onto polytetrafluoroethylene vascular grafts. Seeding efficiency was significantly better in all groups of coated grafts, at all times (10, 30, 60, and 120 minutes), compared to uncoated controls (p less than 0.01). Overall, fibronectin at a concentration of 20 micrograms/ml was found to be the most efficient in terms of cell attachment and cost since any further increase in concentration was not accompanied by increased cell attachment. We now routinely use fibronectin at a concentration of 20 micrograms/ml to coat our grafts before endothelial cell seeding.

Blood Vessel Prosthesis↗

A computerised personal audit for surgical trainees.

A computerised personal audit for surgical trainees has been devised to supplement the newly introduced log books of operations performed. The audit uses a standard database programme and an IBM-PC compatible microcomputer. For ease of entry, the principle diagnosis, operation and any complication are entered in the form of a simple code with the help of an on-screen index. The system has been used for three years by one surgical trainee, with a total of 1,500 operations now on record. Rapid retrieval of an individual patient's details or a list of any data combination required is possible. The operative log book thus becomes part of a powerful personal audit from which surgical trainees can assess their experience and results.

General Surgery↗

Attachment of indium-111 labelled endothelial cells to pretreated polytetrafluoroethylene vascular grafts.

This study investigated the effect of different surface coatings on endothelial cell attachment to polytetrafluoroethylene (PTFE) vascular grafts. Small segments of PTFE vascular grafts were precoated with one of a number of substances: gelatin, poly-l-lysin, fibronectin, or collagen type I, III or IV. Indium-111 labelled endothelial cells were then seeded on to the grafts and left for either 10, 30, 60 or 120 min. The unattached cells were removed and the degree of cell attachment was calculated. All coatings were significantly better at enhancing endothelial cell attachment at all times compared with controls, and fibronectin was significantly better as a coating material than any other material used. By pretreating with a substance such as fibronectin, the number of endothelial cells attaching to PTFE vascular grafts can be greatly increased, thereby enhancing the cell seeding process.

Blood Vessel Prosthesis↗

A study of the mortality from ruptured abdominal aortic aneurysms in a district community.

In a 6-year period (1982-1987), 197 cases of ruptured abdominal aortic aneurysm were identified in the area covered by the Swindon Health District. Of these, 135 (69%) reached hospital alive, 88 (45%) were operated on, and only 28 (14%) survived. This represents an overall mortality of 86%. In comparison, the mortality from elective aneurysm repair for the same period was only 3.3%. These findings suggest that early detection of aortic aneurysms, leading to elective rather than emergency repair, would be of much greater benefit than the small increase in overall survival one would expect from improving treatment in cases of rupture.

Aged↗