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Biomedical subjects

K G Burnand

Publications and source records attributed to K G Burnand.

At least 19 recordsLinked to original sources

The tissue plasminogen activator and urokinase response in vivo during natural resolution of venous thrombus.

PURPOSE: The aim of this study was to measure the distribution of endogenous plasminogen activators during thrombolysis with an endothelial-conserving model of laminated thrombosis. METHODS: Thrombi were raised in the inferior vena cava of rats with thrombin and flow reduction. The thrombi, adjacent vein wall, and distant veins (the superior vena cava) were removed at intervals from 1 hour to 21 days from formation and then cryohomogenized and assayed with specific bioimmunoassays for tissue-type (t-PA) and urokinase-type plasminogen activators (u-PA). RESULTS: The measured t-PA activity of the vein wall around the thrombus was reduced compared with the control inferior vena cava at 4 days. Both the u-PA and t-PA content of the thrombus increased progressively during thrombolysis. The t-PA activity increased significantly in the distant vein walls in the animals with thrombi. Immunocytochemistry and in situ hybridization localized the t-PA to a mononuclear cell infiltrate and showed up-regulation of mRNA for rat t-PA in these monocytes. CONCLUSIONS: The local plasminogen activator response was predominantly within the thrombus itself. Increased t-PA activity was additionally found in distant veins but was reduced in the vessel wall adjacent to the thrombus. This is the first report to show that u-PA activity is increased within organizing thrombus in vivo and that most of the t-PA activity is localized to a monocyte infiltrate.

Animals

The response of the vessel wall to thrombosis: the in vivo study of venous thrombolysis.

The vessel wall is the site of synthesis and regulation of the fibrinolytic system, and this delicate process is overwhelmed by occlusive thrombosis in veins. The endothelium may or may not survive thrombus formation, but has strong powers of regeneration, and is subsequently vital to the process of recanalizing the vessel. The endogenous fibrinolytic response to venous thrombosis is not well delineated but appears to involve both the newly formed endothelium within and beneath the organizing thrombus, together with an increase in tissue plasminogen activator synthesis or storage in distant uninvolved veins. The further use of thrombus models in which the endothelium is not definitely damaged should enable greater understanding of its role. Immunocytochemistry and in situ hybridization may be helpful in defining some of the unanswered questions.

Animals

The distribution of atherosclerosis in the lower limbs.

Sixty-seven consecutive aortograms in non-diabetic patients were studied to establish the distribution of atherosclerosis in the arteries of 134 lower limbs. Prolonged filming and multiple exposures of the feet showed ankle vessels in 131 of the limbs (98%) and a pedal arch or collaterals in 126 (93%). In 51% of the limbs at least one of the calf arteries was occluded and only 24% had two patent arteries at ankle level. The pedal arch was complete in only 16%. The patency rate of the pedal arch was similar in all three symptom groups (p greater than 0.05). Two separate analyses were performed. The first was based on symptoms. Critical ischaemia was present in 18 limbs (13%), claudication in 69 limbs (52%) and 47 limbs were symptomless (35%). The second analysis was based on the sites of major occlusion. Occlusions were already present in 81% of the symptomless limbs, predominantly in the distal vessels. In limbs with claudication or critical ischaemia there were more occlusions above the knee (77 and 89%, respectively) than in limbs without symptoms (36%) (chi 2 = 27.60, p less than 0.001). Occlusion of the popliteal artery was significantly more frequent in the patients with symptoms of critical ischaemia (50%) than in either of the other two groups (chi 2 = 15.61, p less than 0.001). Atherosclerosis appears to develop in the small vessels of the calf and foot at an early stage. The extent of this involvement may influence the progression of symptoms and the outcome of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Emergency treatment of tracheal tear during pharyngolaryngectomy.

Longitudinal tracheal tear (of the trachealis muscle), an unusual but acknowledged complication of pharyngolaryngectomy, was encountered during a total pharyngo-oesophagolaryngectomy with gastric replacement. Due to serious ventilatory difficulties a rapid repair was required to obtain an airtight seal to allow continued mechanical ventilation. A reinforced polytetrafluoroethylene (PTFE) vascular graft was used as an intratracheal stent to seal the air leak. This technique proved effective and the tracheal defect had healed by the time the stent was removed 10 days later.

Carcinoma, Squamous Cell

Influence of phlebographic abnormalities on the natural history of venous ulceration.

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.

Adult

Measurement of the healing of venous ulcers.

The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r = 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments.

Adult

Transcutaneous oxygen tensions in assessing the treatment of healed venous ulcers.

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.

Adult

Calf pump function in patients with healed venous ulcers is not improved by surgery to the communicating veins or by elastic stockings.

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.

Adult

Visualization of the plantar arch by aortography: technique and value.

Arteriograms of the feet in 100 consecutive, routine aortograms in patients with leg ischaemia were analysed to assess the frequency with which the plantar arch was visualized. The technique used involved a long injection time, a large volume of contrast medium and slow filming. The plantar arch was demonstrated in 75% of feet, shown to be occluded in 12% and not demonstrated for technical reasons in 13%. The importance of the integrity or otherwise of the plantar arch is emphasized in assessing patients for distal bypass grafts. It is recommended that an attempt be made to demonstrate the plantar arch in all patients undergoing aortography for ischaemia of the legs.

Adult

Tissue plasminogen activators in breast cancer.

Increased levels of tissue fibrinolytic activity have been detected in some malignant tumours and they have been implicated in metastatic spread. We have investigated tissue plasminogen activator (tPA) and urokinase (UK) in 26 breast carcinomas and 13 benign breast biopsies. Tissue extracts were analysed for overall fibrinolytic activity on fibrin plates and by fibrin-overlay zymography after electrophoresis on SDS-PAG. Supernatants of the extracts were analysed by an antigenic immunoassay (ELISA) and a functional bioimmunoassay (BIA) using polyclonal antibodies. Total ELISA and BIA results correlated (P less than 0.001) and all the tissues contained similar tPA levels. Malignant extracts contained significantly increased UK compared with benign extracts (1.60 +/- 0.37 iu, 0.36 +/- 0.16 iu; P less than 0.002). Zymography showed no high molecular weight inhibitor complexes and UK was almost exclusively confined to the malignant tissues (P much less than 0.02). The results suggest that malignant transformation of breast tissue is associated with the significantly increased production of UK. This may be responsible for the characteristics of malignancy or it may be a growth factor.

Breast Neoplasms

Early diagnosis of femorodistal graft stenoses.

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.

Adult

Reduced response of cerebral blood flow to hypercapnia: restoration by extracranial-intracranial bypass.

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.

Aged

Changes in the apparently normal limb in unilateral venous ulceration.

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.

Adult

Effect of carotid endarterectomy on cerebral blood flow and its response to hypercapnia.

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.

Aged