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Background: The aim was to assess the quality of life (QoL) of patients who had surgery for primary lymphoedema., Methods: A QoL questionnaire was administered to patients who had surgery between 1981 and 2003 (retrospective group) and between 2003 and 2006 (prospective group)., Results: The response rate was 70.3 per cent (109 of 155 patients): 88 patients had limb reduction (78, retrospective; ten, prospective) and 21 had genital reduction (13, retrospective; eight, prospective). Forty-nine patients (63 per cent) who had limb reduction studied retrospectively reported satisfaction with the procedure and most of these would opt for surgery again. In the prospectively studied group, nine of ten patients reported improved limbs, and seven would opt for surgery again. Nineteen of 21 patients who had genital reduction would choose to have surgery again if needed (11 of the retrospectively assessed group and all of the prospective group). Patients' perception that surgery was worthwhile was greater in both of the prospectively assessed groups (P = 0.013)., Conclusion: Surgery for severe lymphoedema improved QoL at early assessment. This, however, may not be sustained. Genital reduction appeared to provide greater benefit than limb reduction.

Background: The presence of fibrous tissue in poorly healing venous leg ulcers suggests abnormal collagen metabolism. The aim was to determine whether there were differences in collagen turnover and matrix metalloproteinase (MMP) activity between ulcers that healed, those that did not heal and normal skin., Methods: Biopsies were taken from the ulcers of 12 patients whose venous ulcers went on to heal and 15 patients whose ulcers failed to heal despite 12 months of compression bandaging. Biopsies were taken from 15 normal controls. Collagen turnover (collagen III N-terminal propeptide (PIIINP) and degraded collagen), and total MMP, MMP-1 and MMP-3 activities were measured., Results: PIIINP and degraded collagen levels were higher in ulcers that healed compared with lesions that failed to heal (P = 0.005 and P < 0.001 respectively) and normal skin (P = 0.003 and P < 0.001). MMP-1 activity was also higher in healing ulcers than resistant ulcers (P < 0.001) and normal skin (P < 0.001). Significantly more total MMP activity was present in all ulcers than in normal skin (P < 0.001), but there was no difference in total MMP (and MMP-3 activity) between ulcers that healed and those that did not., Conclusion: Rapidly healing venous leg ulcers had increased collagen turnover and MMP-1 activity, which appeared to differentiate them from those that failed to heal within 12 months., (2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: The aim of this study was to examine the effect of statin treatment on the activity of proteases in the wall of abdominal aortic aneurysms (AAAs)., Methods: The activities of matrix metalloproteinases (MMPs) 9 and 3, cathepsins B, H, K, L and S, and the cystatin C level were measured in extracts of AAA wall taken from 82 patients undergoing AAA repair; 21 patients were receiving statin treatment before surgery. All values were standardized against soluble protein (SP) concentration in the extract, and reported as median (interquartile range) or mean(s.e.m.)., Results: The two groups had similar demographics. Reduced activity of MMP-9 (43 (34-56) versus 80 (62-110) pg per mg SP; P < 0.001), cathepsin H (183 (117-366) versus 321 (172-644) nmol 4-methylcoumarin-7-amide released per mg SP; P = 0.016) and cathepsin L (102 (51-372) versus 287 (112-816) micromol 7-amino-4-trifluoromethylcoumarin released per mg SP; P = 0.020) was found in the statin-treated aortas compared with AAAs from patients not taking a statin. The statin-treated group had lower MMP-3 activity, but this did not reach statistical significance (P = 0.053). Cystatin C levels were higher in statin-treated aortas than in controls (41.3(3.1) versus 28.9(2.1) ng per mg SP; P = 0.003)., Conclusion: Statins decreased the activity of proteases that have been implicated in aneurysm disease., (2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Deep vein thrombosis of the leg affects 1-2 per cent of the population with an annual incidence of 0.5-1 per 1000. It presents with non-specific symptoms and signs making clinical diagnosis difficult. Techniques to image and diagnose this condition are advancing rapidly., Methods and Results: A literature review from 1980 to 2007 was undertaken using PubMed, The Cochrane Library, Medline and Embase. The most frequently used diagnostic test is duplex ultrasonography which is accurate above the knee and has a low cost, but is limited by inaccuracy when assessing the pelvic and distal veins and in diagnosing a new thrombosis in the post-thrombotic limb. Magnetic resonance imaging (MRI) and sonographic elasticity imaging are more recent techniques that have shown promise in overcoming these limitations. However, their availability is currently restricted because they are expensive. Computed tomography (CT) is sensitive, specific and provides good imaging of the pelvis. It has the advantage that it can be performed at the same time as CT pulmonary angiography., Conclusion: MRI has some specific advantages over duplex ultrasonography, but requires refinement before it can be used clinically. Venography or CT venography should be considered when duplex scanning is inadequate., (2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: The aim of this study was to determine the success of excision and meshed skin grafting for chronic leg ulcers. The effects of different ulcer aetiology and ulcer size on outcome were also assessed., Methods: All patients who had excision and mesh grafting for chronic leg ulceration between January 1996 and December 2004 at St Thomas' Hospital were reviewed. Recurrence was classified as any breakdown of the ulcer during follow-up., Results: Sixty-two patients with 100 chronic leg ulcers underwent operation. Seventy-two of the ulcers were venous and the median ulcer size was 36 (range 1.5-192) cm2. Only three patients left the hospital with their ulcers unhealed, but ulcers had recurred in 28 (28 per cent) by 2 months. A further 17 ulcers recurred later, with just over half (55 per cent) remaining healed by 5 years. There was no difference between the recurrence rates of venous ulcers and ulcers of other aetiologies (P=0.980), or large (more than 10 cm2) and small ulcers (P=0.686)., Conclusion: Wide local excision and meshed skin grafting benefitted over half of these patients with refractory leg ulcers. Recurrence was most likely to occur in the first 2 months and, provided that ulcers were healed at this time, there was a low rate of further breakdown., (Copyright (c) 2006 British Journal of Surgery Society Ltd.)

Background: Carotid endarterectomy reduces the risk of stroke and death in patients with severe carotid artery stenosis. This study examined whether the technique used to close the arteriotomy influenced the rate of perioperative transient ischaemic attack (TIA), stroke or death., Methods: A cohort of 236 patients undergoing carotid endarterectomy at a single centre was studied; 117 patients had primary closure of the arteriotomy and 119 patients in a sequential series had closure with a Dacron patch. A standard endarterectomy with completion intraoperative duplex imaging and digital subtraction angiography was used throughout., Results: Patch closure was associated with a significant reduction in the 30-day combined death, stroke and TIA rate: 10.3 per cent for primary closure versus 2.5 per cent for patch closure (P = 0.017). The risk of any cerebral event (stroke or TIA) was also significantly reduced (7.7 versus 1.7 per cent; P = 0.033). Residual stenosis on completion angiography was more common after primary closure (24.6 versus 7.4 per cent; P = 0.003)., Conclusion: Dacron patch closure had a higher technical success rate on completion imaging and was associated with a significant reduction in the risk of perioperative stroke, TIA and death., (Copyright (c) 2005 British Journal of Surgery Society Ltd.)

Background: Symptomatic stenosis of the supra-aortic trunks (subclavian, innominate and common carotid arteries) can be treated by angioplasty/stenting or surgical bypass. The aim of this study was to compare the initial success and outcome of these two types of treatment., Methods: A prospective database was used to collect information on the presentation, initial success, complications and outcome in 76 patients treated in a single centre between 1983 and 2003., Results: Thirty-five surgical extra-anatomic bypasses were performed, 13 carotid to carotid, 14 carotid to subclavian, two carotid to axillary, three axillary to axillary, one subclavian to axillary and two subclavian to subclavian. One graft occluded after 19 years. No limbs were amputated and no patient had a stroke. The secondary patency rate was 97 per cent at a mean follow-up of 5 years. Forty-one angioplasties were attempted, 34 of the left subclavian, six of the right subclavian and one of the innominate artery. Angioplasty for six subclavian occlusions was unsuccessful. Twenty-seven of 33 arteries remained patent at a mean follow-up of 4 years after a successful endovascular procedure., Conclusion: Extra-anatomic bypass for supra-aortic trunk disease has a better patency than angioplasty, with a comparable complication rate., (Copyright (c) 2004 British Journal of Surgery Society Ltd)

Background: Both four-layer and three-layer paste bandages are widely used in the treatment of venous leg ulcers. The aim of this study was to compare the efficacy of these two bandaging regimens., Methods: The study was a prospective, randomized, open comparison of a consecutive cohort of 133 patients with venous ulcers. Participants were stratified by ulcer size into one of three groups and were randomized within each group to receive either three-layer paste or four-layer bandages. All patients were followed for 1 year. The time taken to complete ulcer healing was the primary endpoint. The time taken to apply the bandages, comfort, tolerability and cost were also assessed. Analysis was performed on the basis of intention to treat., Results: Ulcers healed completely in 51 (80 per cent) of 64 patients treated with three-layer paste bandages compared with 45 (65 per cent) of 69 patients treated with the four-layer regimen (P = 0.031). This difference developed only after 20 weeks of treatment. The median times to complete healing were 12 weeks for three-layer and 16 weeks for four-layer treatment (P = 0.040). Results of venous function tests, including half-refilling times, were similar in the two groups., Conclusion: Three-layer paste bandages were significantly more effective at healing venous ulcers than the four-layer regimen in this study., (Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: Angiogenesis, the formation of new from existing capillaries, is an important mechanism in venous ulcer healing. The aim of this study was to determine whether venous leg ulcer wound exudates stimulate or inhibit angiogenesis., Methods: Fluid exudate was obtained from 16 venous ulcers over a 4-h interval. Five of the ulcers had not healed after more than 1 year of compression bandaging, and five were rapidly healing ulcers. As a control, acute wound fluids were collected from subcutaneous drains in seven patients. Vascular endothelial growth factor (VEGF) at 2 ng/ml acted as a positive control. Tubules stained with an antiendothelial antibody were quantified using an image analysis system. The extent of angiogenesis was expressed as the ratio of the mean tubule length in the test wells over that in blank control wells., Results: Venous ulcer exudates significantly inhibited angiogenesis (mean (95 per cent confidence interval) 0.72 (0.48 to 0.96)) compared with acute wound fluids (2.48 (0.86 to 4.10)) (P < 0.002) and VEGF (1.47 (1.32 to 1.61)) (P = 0.01). Exudates from the five non-healing venous ulcers inhibited angiogenesis (0.31 (0.15 to 0.46)) significantly more than exudates from the five rapidly healing venous ulcers (0.93 (0.21 to 1.65)) (P = 0.03)., Conclusion: Fluid exudate from venous ulcers, in particular those that healed slowly, inhibited experimental angiogenesis in this study.

Background: The incidence of long saphenous vein (LSV) duplication has not been clearly established. This anomaly could have implications for recurrence after varicose vein surgery., Methods: Some 103 saphenograms obtained in 85 patients being considered for peripheral arterial bypass surgery were reviewed. Non-ionic contrast medium was injected directly into the vein or its tributaries at the ankle. Duplications of the LSV and their relation to thigh and calf perforator veins were assessed and recorded by two independent observers., Results: There was evidence of duplication of the LSV in 50 (49 per cent) of the 103 saphenograms. Most duplications were present in the thigh (88 per cent) and the most common pattern was a closed loop (54 per cent). Perforator veins were connected to one branch of the duplication in 42 per cent of the legs (20 per cent of all 103 legs); in half the perforator vein was connected to the non-dominant branch of the duplication. Only ten of the 18 patients who had bilateral saphenograms had duplications in both legs, and only one patient had the same pattern of duplication on both sides., Conclusion: The incidence of LSV duplications is higher than previously reported.

Background: Many venous ulcers are healed by the application of external compression. It has been suggested that bandages capable of producing greater compression enhance healing. The aim of this study was to compare the time to total healing of venous ulcers in two groups of patients treated with different compression regimens in a randomized prospective trial., Methods: A total of 112 patients was studied and all were treated with a zinc-impregnated paste bandage applied directly to the ulcer. Fifty-seven patients had the paste covered by Tensopress and 55 by Elastocrepe bandages. Both groups had a tubular bandage applied over the top to retain the bandage in place. All ulcers were stratified and randomized within one of three size groups. The 'venous' aetiology of the ulcer was confirmed on completion by calf pump function tests., Results: By 26 weeks, 58 per cent of the patients treated with Tensopress and 62 per cent of those treated with Elastocrepe bandages were healed. The median healing times were 9 and 9.5 weeks respectively. Similar numbers of patients were excluded or withdrawn from both groups. Large ulcers healed significantly more slowly than small ulcers., Conclusion: There was no significant improvement in venous ulcer healing using higher compression elastic bandages.

Background: Isotope lymphography has largely replaced contrast lymphography in the diagnosis of lymphoedema. Its accuracy has only been assessed in small studies and it is not known if it can identify patients with a proximal lymphatic obstruction who may be suitable for lymphatic bypass surgery., Methods: Three hundred and ninety-five patients suspected to have lymphoedema were investigated by isotope lymphography between 1985 and 1995. Contrast lymphography was also carried out in 29 of these patients because the isotope results were thought to be misleading, or because lymphatic bypass surgery was being considered., Results: In the 29 patients who had both investigations isotope lymphography detected 20 of 24 abnormal lymphatic systems. Four legs with obstructed groin lymphatics were reported as normal. Two legs with normal contrast lymphograms were erroneously diagnosed as having lymphoedema in the isotope study. Detectable groin nodes on the scintigrams were indicative of either normal lymphatics or proximal lymphatic obstruction. An increase in isotope uptake over 30-60 min of less than 50 per cent, or a total absence of isotope within groin nodes, was a sensitive indicator that patients were unsuitable for lymphatic bypass surgery., Conclusion: Isotope lymphography is a moderately sensitive test for lymphoedema, which will mistakenly classify some normal legs as lymphoedematous. It will usually correctly identify patients who are suitable for lymphatic bypass surgery.

Background: Duplex ultrasonography is increasingly used as the sole method of imaging before carotid endarterectomy. This study investigated the measured degree of stenosis in the contralateral carotid artery before and after operation., Methods: Duplex-derived peak systolic velocity (PSV), end-diastolic velocity (EDV) and internal carotid artery/common carotid artery (ICA/CCA) velocity ratios were measured in the contralateral unoperated ICA before 131 consecutive unilateral endarterectomies and compared with preoperative angiographic findings. Three months later duplex scans were repeated to assess whether there had been any alteration in the severity of the stenosis in the contralateral unoperated artery., Results: Bilateral ICA disease (greater than 50 per cent stenosis) was present in 50 patients (38 per cent). Three months after operation, ultrasonography of the 105 unoperated, patent, contralateral arteries showed a decrease in mean(s.d.) PSV (1.21(0. 83) versus 1.07(0.69) m/s; P < 0.01) and EDV (0.41(0.29) versus 0. 35(0.24) m/s; P < 0.01). This resulted in 14 (42 per cent) of 33 patients with contralateral disease being downgraded to a less severe category of stenosis. Use of the ICA/CCA velocity ratio prevented overestimation in eight of the 14 patients, while preoperative angiography correctly classified 13 of the 14 patients., Conclusion: Bilateral carotid artery disease can cause overestimation of the severity of stenosis by duplex ultrasonography if absolute velocity is used as the main criterion.

BACKGROUND: Duplex ultrasonography is increasingly used as the only investigation before endarterectomy for internal carotid artery stenosis. Contralateral disease is present in approximately 20 per cent of these patients and may lead to overestimation of the carotid stenosis by duplex imaging before surgery. This problem was investigated in the present study. METHODS: Peak systolic and diastolic duplex velocities were compared with angiographic data before 126 consecutive carotid endarterectomies (106 symptomatic, eight asymptomatic, 12 precoronary revascularization). Some 3 months later velocities were repeated to assess whether endarterectomy of a diseased carotid artery affected contralateral velocity measurements. RESULTS: Significant contralateral carotid disease was present in 36 (29 per cent) of the 126 preoperative angiograms (14 occlusions, 22 stenoses greater than 60 per cent). Three months after operation 119 of the endarterectomy sites were widely patent. Duplex ultrasonography of the 105 non-operated patent contralateral arteries showed a decrease in mean(s.d.) peak systolic and diastolic velocities from 1.21(0.83) and 0.41(0.29) m s-1 before operation to 1.08(0.69) and 0.35(0.24) m s-1 respectively (P < 0.01, paired t test). Preoperative duplex velocities had indicated contralateral disease of greater than 50 per cent stenosis in 34 cases, but 14 of these were reclassified to less severe disease following surgery. Thirteen of these had been correctly classified by preoperative angiography while use of systolic and diastolic internal/common carotid artery velocity ratios reduced the overestimation of stenosis in eight of the 14 cases. CONCLUSION: Bilateral carotid artery disease is common and may lead to overestimation of stenosis by duplex ultrasonography, which should therefore be supplemented with other modes of imaging.

Background: It is still unclear what initiates aneurysmal dilatation and what determines whether or not an aneurysm will continue to expand and rupture. Early detection and operative repair of an abdominal aortic aneurysm (AAA) still remains the only effective means of reducing the high mortality rate associated with the condition. Endovascular techniques are being developed in an attempt to reduce the mortality rate associated with elective repair. A variety of animal models and experimental techniques have been described in the investigation of the pathophysiology of AAA and in the development of improved endovascular surgical and pharmacological therapies. This article discusses these models and techniques, their advantages and some of the problems encountered in extrapolating experimental findings to the human condition., Methods: This review is based on a search of the Medline database from 1966 to March 1998 using recognized key words and text words. A further search was then conducted on references quoted within selected relevant publications., Results and Conclusion: Treatment of rodent aortas with intraluminal elastase or periaortic calcium chloride creates reproducible aneurysms that have certain similarities to the human pathology; such aneurysms have been favoured in the investigation of the pathophysiology of aneurysm expansion. However, these models lack several of the prominent features of the human lesion, such as atherosclerosis and intraluminal thrombosis. The development of gene knockout mice may lead to a more analogous aneurysm formation, with associated atherosclerosis. Many large animal models have been used in the development of endovascular techniques but, in general, these do not mimic the human pathophysiology and fail to predict medium- and long-term complications.

Background: Despite the theoretical advantages of coating knitted grafts with a material designed to reduce blood loss, their performance has not been directly compared with woven grafts in a prospective randomized trial. The aim of this study was to compare the graft handling qualities and operative blood loss of the two types of arterial prosthesis, as well as complication rate and patient survival at 1 year., Methods: A total of 267 consecutive patients having surgery for occlusive or aneurysmal disease of the aortoiliac arteries were randomized to receive woven (141 patients) or knitted collagen-impregnated Dacron (126 patients) grafts. Graft patency was assessed on discharge and at 1 year by duplex imaging., Results: Mean(s.d.) intraoperative blood loss was statistically greater with woven grafts (1690(1424) ml) compared with knitted (1363(1172) ml) (P = 0.049). An insignificant 1-year increase in mean(s.d.) graft diameter of 1.2(0.2) mm was found at the distal anastomosis in the knitted group. There was no difference in graft patency between the groups and only one graft became infected., Conclusion: This study suggests that knitted and woven grafts have similar clinical performance and therefore the less expensive material (woven) should usually be selected unless haemorrhagic complications are anticipated.

Background: This review examines the history, incidence, aetiology and pathology of recurrent carotid stenosis, and assesses the methods and results of managing patients with this condition., Methods: Over 200 references were retrieved from Medline from 1966 to 1996. Data were collected which reported the incidence, timing, method of diagnosis, follow-up, percentage of patients with symptoms and the indications for revisional surgery. The stroke rate and operative mortality rate following revisional carotid surgery were also recorded., Results: The overall incidence of symptomatic recurrent stenosis ranged from 0 to 8.2 per cent, with a symptomless recurrence rate between 1.3 and 37 per cent. Forty-three (78 per cent) of 55 studies indicated that revisional surgery was performed on patients with symptoms; only 21 (38 per cent) of 55 studies indicated that operations were carried out on asymptomatic patients. The stroke rate and mortality rate after 511 revisional procedures were 3.9 and 1.0 per cent respectively., Conclusion: Symptomatic recurrent stenosis is rare but some patients may benefit from revisional surgery. Surgery for symptomless carotid restenosis should be considered only if a multicentre trial can demonstrate clear benefit in terms of patient survival or stroke reduction.

Background: Duplex ultrasonography has become the optimal non-invasive method of assessing the deep venous system of the leg. The stimuli used to promote reverse flow, subject positioning, and the veins scanned have varied between studies. Reverse flow of less than 0.5 s is accepted as 'normal', however, all published studies have demonstrated 'normal' subjects with deep vein reverse flow exceeding this time. The aim of this study was to establish the duration of reverse flow in all deep vein segments, and to determine the optimal method of eliciting reverse flow in individuals with proven normal deep vein function., Methods: Duplex scanning was used to detect the presence and duration of reverse flow in the superficial femoral, popliteal and posterior tibial veins of 61 legs with normal venous function. The veins were scanned with each subject inclined at 10 degrees, 45 degrees and standing erect. The abrupt release of distal tourniquet compression and the Valsalva manoeuvre were used as stimuli for reverse flow., Results: There was significantly less reverse flow in distal veins than in proximal veins when the subject was scanned at 10 degrees and 45 degrees. Median (range) reverse flow in the femoral vein at 10 degrees was 0.21 (0-1.18) s, posterior tibial vein 0.08 (0-0.67) s, (P < 0.0001); in the femoral vein at 45 degrees was 0.14 (0.04-2.14) s, posterior tibial vein 0.07 (0-0.56) s, (P < 0.0001). The duration of reverse flow was significantly less in the superficial femoral and popliteal veins when the subjects were erect than when inclined at 10 degrees and 45 degrees. Median (range) reverse flow in the femoral vein at 10 degrees was 0.21 (0-1.18), and when standing 0.1 (0-1.36) (P < 0.0001); below-knee popliteal vein at 10 degrees was 0.15 (0.04-1.95) s, and when standing 0.10 (0-1.03) (P = 0.0004). Reverse flow of more than 0.5 s was never elicited in the posterior tibial veins if the subject stood, nor did it occur in the popliteal vein during a Valsalva manoeuvre., Conclusion: The optimal sites to assess deep vein reverse flow are the posterior tibial vein following removal of distal compression with the patient standing, and the popliteal vein during a Valsalva manoeuvre, as retrograde flow more than 0.5 s does not occur in subjects with normal venous function.

Thirty patients with peripheral arterial embolism underwent conventional transthoracic echocardiography. Transoesophageal echocardiography was also performed in ten of the same patients. The detection rate of cardiac abnormalities considered responsible for embolism was five of 20 in patients who received only transthoracic echocardiography and eight of ten in those who underwent transoesophageal echocardiography. One abnormality was detected by transthoracic echocardiography in the ten patients who received both tests, while eight cardiac or aortic abnormalities were discovered by transoesophageal echocardiography (P < 0.05). Transoesophageal echocardiography is significantly better than conventional transthoracic echocardiography at detecting cardiac sources of peripheral arterial embolism.

Compartment syndrome is a rare but serious complication of prolonged pelvic surgery. Prompted by two recent cases the authors studied the effect of limb angulation and elevation on Doppler ankle artery pressure and compartment pressure in ten normal subjects. Mean ankle pressure when supine was 130.5 (95 per cent confidence interval (c.i.) 124.5-136.5) mmHg and fell to 77.2 (95 per cent c.i. 64.6-89.8) mmHg in the Lloyd-Davies position with 10 degrees of head-down tilt. Reversing table tilt to bring the ankle elevation to 0 degrees in Lloyd-Davies supports restored mean ankle pressure to 114.3 (95 per cent c.i. 105.5-122.9) mmHg (P < 0.001). Placing the lower limb in calf supports was found to increase the mean intracompartmental pressure from 3.0 (95 per cent c.i. 1.2-4.8) mmHg to 11.6 (95 per cent c.i. 9.1-14.1) mmHg. Reversing table tilt significantly restores limb perfusion in patients undergoing prolonged pelvic surgery with the legs elevated and may protect against subsequent compartment syndrome.

Urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA) were assayed in biopsies from the base, edge and adjacent skin of ischaemic and venous ulcers using a functional bioimmunoassay and a standard immunoassay. Two series of 14 biopsies were examined: from seven venous and seven ischaemic ulcers in the first series, eight venous and six ischaemic in the second. It was found that tPA was detected in only four samples of ulcer edge using the bioimmunoassay and in no sample by the standard immunoassay. By contrast, uPA was detected in all but one ulcer edge biopsy and at a significantly lower median concentration in the adjacent skin (16.9 units/g) than the ulcer edge (26.1 units/g) or base (32.3 units/g) (both P < 0.01). Levels of uPA were greater in the edge and base of venous compared with ischaemic ulcers. The predominant plasminogen activator in chronic leg ulcers is uPA; this activator may play an important role in wound healing.

Eighty-five limbs in 73 patients with a healed venous ulcer were assessed by ascending and descending phlebography, foot volume plethysmography and transcutaneous oxygen measurements. Forty-four limbs had post-thrombotic changes on ascending phlebography. In 24 (28 per cent) these extended into the femoral vein, while in 20 (24 per cent) only the calf veins were involved. In the 41 limbs (48 per cent) with normal deep veins on ascending phlebography, 11 had evidence of localized incompetence of the calf communicating veins, 14 had either long saphenous incompetence, deep vein reflux to the level of the knee or below, or both of these abnormalities, and 16 limbs had no phlebographic abnormalities. However all limbs had a decreased half volume refilling time on foot volume plethysmography. Limbs with post-thrombotic changes extending into the femoral vein were associated with a significantly longer history of ulceration and more ulcer recurrences than limbs with calf vein damage (P less than 0.05 for each) and limbs with normal deep veins (P less than 0.01 for each). However, these limbs did not have lower transcutaneous oxygen ratios or longer times to achieve ulcer healing. Ascending phlebography identified a group of limbs with extensive post-thrombotic changes in which there was a higher incidence of ulcer breakdown, but this was not associated with a delay in ulcer healing.

Transcutaneous oxygen tension (Ptc,O2) was assessed as an indicator of risk of reulceration in 68 limbs with healed venous ulcers. Ptc,O2 was also used to assess two methods of ulcer prophylaxis. Measurements were made over the gaiter skin, the healed ulcer and the upper arm. The results were expressed as a ratio of the lower limb readings over those taken from the arm. Patients were randomized, after the ulcer had healed, to elastic stockings and stanozolol, or elastic stockings and surgical ligation of incompetent superficial veins. Patients who declined to participate in the study were prescribed elastic stockings only. Those limbs remaining healed at 12 months had Ptc,O2 ratios remeasured. The Ptc,O2 ratios from limbs that reulcerated were not significantly lower than those from limbs remaining healed. The Ptc,O2 ratio was significantly increased in limbs treated by stanozolol and elastic stockings (P less than 0.05) and by surgery and elastic stockings (P less than 0.05). There was no significant increase in Ptc,O2 in limbs treated by elastic stockings alone. In those treated by surgery and elastic stockings, there was a significant improvement in limbs with normal deep veins (P less than 0.01), but not in limbs with post-thrombotic changes on ascending phlebography. Although these two methods of ulcer prophylaxis improve the Ptc,O2 ratio, a high ratio has not been shown to be beneficial in preventing ulcer recurrence.

Cefuroxime is a broad spectrum cephalosporin antibiotic. An intravenous injection of cefuroxime 1.5 g was administered to 25 patients after induction of anaesthesia for cholecystectomy. Concentrations of antibiotic were measured and the mean levels in microgram/ml found to be: serum 120.5, common bile duct bile 42.8, gallbladder bile 5.4, gallbladder wall 39.2. The drug levels exceeded the minimum inhibitory concentrations for most organisms commonly encountered in the biliary tract. There was no difference in cefuroxime levels in bile from functioning or non-functioning gallbladders. It is suggested that the diffusion of antibiotic into and out of the inflamed gallbladder is similar to that in abscesses and in experimental tissue cages. No side effects, toxicity or wound infections occurred.

An increased number of skin capillaries has been found in human skin subjected to sustained venous hypertension. To investigate this observation, venous hypertension was produced in the hind limb of Greyhounds by fashioning an arteriovenous (AV) fistula between the femoral vessels. This caused an increase in the number of capillaries in the skin of the lower leg. The capillary permeability of normal legs and legs subjected to chronic venous hypertension was then studied by observing the movement of radioactive molecules from the plasma to the fluid within Guyton capsules. Fibrinogen, a large molecule, leaked out of the capillaries significantly faster in the limbs with a high venous pressure and an enlarged capillary bed. It is suggested that the increase in the size and permeability of the dermal skin capillaries secondary to prolonged venous hypertension is the cause of lipodermatosclerosis and venous ulceration.

The changes in foot vein pressure during exercise have been measured in 30 normal legs and 109 legs with varicose veins or postphlebitic changes and correlated with the number of capillaries visible in a histological section of skin from the ulcer-bearing area. There was a significant correlation between the inability of the calf pump to reduce foot vein pressure during exercise and the number of capillaries in the skin. It is suggested that the increased number of capillaries secondary to venous hypertension during exercise may be the prime cause of the nutritional abnormalities that eventually cause a venous ulcer.

Sixty-six patients with well-differentiated thyroid carcinomas have been followed up for a minimum of 10 years. A conservative surgical approach was adopted for unsuspected intrathyroid tumours. Twenty-three out of 29 patients (80 per cent) with papillary carcinomas and 18 out of 37 (50 per cent) with follicular carcinomas were alive at the time of review. Although patients with follicular carcinoma have only a moderate overall prognosis, patients with node-negative intrathyroid tumours (unsuspected) treated by conservative resection have a 79 per cent 10-year survival. These survival figures compare favourably with other reported series where all the patients were treated by radical surgery. Early conversion of a conservative resection to a total thyroidectomy for an unexpected tumour does not appear to be warranted since an increased risk of complications is not balanced by an improved outcome. Two patients, with intrathyroid papillary carcinomas who developed tumours in the residual gland more than 5 years after initial lobectomy, successfully underwent further resections of the thyroid remnants, and are disease free more than 9 years later.

Detection and early correction of stenoses following femorodistal bypass grafting may prevent graft occlusion. We studied 43 grafts (36 saphenous vein and 7 human umbilical vein) prospectively by peroperative angiography and then by clinical assessment, post-exercise Doppler ankle pressures and digital subtraction angiography at 1 week, 3 months, 6 months and 1 year. There were 11 grafts inserted for critical ischaemia, 16 for rest pain and 16 for disabling claudication. Four patients died within the year with five patient grafts and these were excluded from the final results. Eight grafts failed during the first year; four within 1 month and a further four subsequently, with no warning alteration of symptoms, ankle Doppler pressure or digital subtraction angiography. Four additional grafts were jeopardized by symptomatic stenoses. Six grafts developed an asymptomatic stenosis of greater than 50 per cent without a change in exercising ankle Doppler pressure. Three symptomatic stenoses were successfully revised but the fourth occluded on conservative management. Three asymptomatic stenoses have also been successfully revised and three have been treated conservatively. Close surveillance of femorodistal grafts is justified by this study but a deterioration in ankle brachial Doppler index was only useful in the patients with recurrent symptoms and was unable to detect half the stenoses of greater than 50 per cent. The detection of these by intravenous digital subtraction angiography might help to avoid graft failure.

Calf muscle pump function was assessed in 41 limbs after venous ulcers had healed. Treatment was then randomized either to ligation of incompetent lower leg communicating veins and ablation of incompetent superficial veins combined with permanent graduated compression elastic stockings, or to graduated compression elastic stockings only. Half volume refilling time (TV1/2) and relative expelled volume (EVrel) measured on foot volume plethysmography were used to assess calf muscle pump function. This was repeated after 12 months. The initial TV1/2 and EVrel were significantly lower than for normal limbs. There was no significant improvement in TV1/2 in either treatment group (Student's t test, P = 0.78, P = 0.19). EVrel did not improve significantly in limbs treated with elastic stockings alone (P = 0.94), but there was a slight but significant improvement in EVrel in limbs treated with surgery and elastic stockings (P = 0.048); however, this was still significantly below the normal range (P less than 0.001). In limbs without phlebographic evidence of post-thrombotic changes, treated with the combination of surgery and elastic stockings, there was a significant improvement in EVrel (P = 0.035), but no improvement was found in limbs with post-thrombotic changes. This small but significant improvement in EVrel in limbs without post-thrombotic changes treated by surgery and elastic stockings may explain the reduced incidence of reulceration that has been found following surgical eradication of the superficial and communicating veins.

Cerebral blood flow, estimated by the xenon clearance technique, has been used to study eight patients before and after extracranial-intracranial (EC-IC) bypass surgery. Response of cerebral blood flow to hypercapnia was also measured to estimate cerebral reactivity, an indicator of cerebral vasodilator reserve capacity. Measurements in all patients were repeated 3 months after surgery. Resting cerebral blood flow was not increased by the operation but cerebral reactivity in the ipsilateral hemisphere was significantly increased in all patients (P = 0.002). Reactivity also increased in the contralateral hemisphere in six of the eight patients (P = 0.065). The response of cerebral blood flow to hypercapnia may prove useful in the selection of symptomatic patients with carotid occlusions or inaccessible stenoses for revascularization by EC-IC bypass.

A number of techniques have been used to diagnose aortic graft-enteric fistulae. These are reviewed and their value assessed. Three patients are described in whom the diagnosis was correctly made from characteristic appearances seen on a computed tomography (CT) scan. Further experience may show that CT scanning has an important role in the detection of this condition.

Forty-seven patients with unilateral venous ulceration have been investigated to determine if any abnormalities were present in the contralateral limbs which had not had lipodermatosclerosis or ulceration. Ascending phlebography in the non-ulcerated limbs showed post-thrombotic changes in 28 per cent and incompetent lower leg communicating veins in 19 per cent. This incidence was not significantly different to the limbs with healed ulceration (45 and 23 per cent respectively, chi 2 test, P = 0.10). Half volume refilling time measured by foot volumetry suggested that 79 per cent of the non-ulcerated limbs had evidence of deep vein incompetence or incompetent lower leg communicating veins, which was again similar to the incidence in the previously ulcerated limbs (85 per cent). Transcutaneous oxygen readings, expressed as a ratio of a reading at a standard site in the gaiter region of the leg over a reading from the upper arm, were significantly lower in non-ulcerated limbs (mean 0.84 +/- 0.26 s.d.) than in a cohort of age and sex matched controls (mean 1.02 +/- 0.14, Student's t test, P less than 0.001), and significantly higher than in previously ulcerated limbs (mean 0.68 +/- 0.31, P less than 0.01). Abnormalities in venous anatomy and function have been shown, in conjunction with evidence of reduced oxygen diffusion, through the gaiter skin before overt skin changes develop.

Cerebral blood flow (CBF) was measured in 14 patients before carotid endarterectomy, 3 h after surgery and 2 days postoperatively using the intravenous xenon-133 technique. In 11 of the patients CBF was remeasured at 6 months and in 8 patients CBF and the response to hypercapnia (5 per cent CO2 in air) was measured pre-operatively and 6 months following surgery. All operations were performed using an intraluminal Javid shunt and internal carotid artery (ICA) 'stump' pressure was recorded. CBF measured at 3 h after endarterectomy revealed a postoperative cerebral hyperperfusion with significantly increased flows in both hemispheres. There was a significant correlation between carotid cross clamping time and ipsilateral hemispheric CBF increase which implied an ischaemic aetiology for the hyperperfusion and supported the routine use of an intraluminal shunt in carotid endarterectomy. Six months after surgery, CBF had returned to its preoperative value but reactivity to CO2 was significantly improved, which suggested that the operation had increased cerebral reserve.