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Biomedical subjects

J H Scurr

Publications and source records attributed to J H Scurr.

At least 19 recordsLinked to original sources
PubMed1999

Endothelial activation response to oral micronised flavonoid therapy in patients with chronic venous disease--a prospective study.

BACKGROUND: Endothelial activation is important in the pathogenesis of skin changes due to chronic venous disease (CVD). Purified micronised flavonoid fraction has been used for symptomatic treatment of CVD for a considerable period of time. The exact mode of action of these compounds remains unknown. AIM: To study the effects of micronised purified flavonoidic fraction (Daflon 500 mg, Servier, France) treatment on plasma markers of endothelial activation. MATERIALS AND METHODS: Twenty patients with chronic venous disease were treated for 60 days with DAFLON 500 mg twice daily. Duplex ultrasonography and PPG was used to assess the venous disease. Blood was collected from a foot vein immediately before starting treatment and within 1 week of stopping treatment. Plasma markers of endothelial activation were measured using commercial ELISA kits. RESULTS: Reduction in the level of ICAM-1, 32% (141 ng/ml: 73 ng/ml) and VCAM 29% (1292 ng/ml: 717 ng/ml) was seen. Reduction in plasma lactoferrin (36% decrease, 760 ng/ml: 560 ng/ml) and VW factor occurred in the C4 group only. CONCLUSIONS: Micronised purified flavonoidic fraction treatment for 60 days seems to decrease the levels of some plasma markers of endothelial activation. This could ameliorate the dermatological effects of (CVD). This could also explain some of the pharmacological actions of these compounds. Our study demonstrates the feasibility of using soluble endothelial adhesion molecules as markers for treatment.

Administration, Oral↗
PubMed1998

Increased plasma vascular endothelial growth factor among patients with chronic venous disease.

Skin damage in the presence of chronic venous disease is partially mediated through leukocytes. The endothelium is activated and exhibits proliferation in the skin. Up-regulation of vascular endothelial growth factor (VEGF) expression in the skin of patients with chronic venous disease has been demonstrated with immunohistologic techniques. Abnormal VEGF expression can have local deleterious effects. The aim of this study was to determine whether patients with chronic venous disease have elevated plasma levels of VEGF. We conducted a prospective study with 30 patients with varicose veins of clinical, etiologic, anatomic, and pathologic class C3 (normal skin, n = 15) and C4 (trophic skin changes, n = 15) and 25 control subjects with no clinical evidence of venous or arterial disease of the lower limb. Blood samples were collected from a foot vein of each subject before and after a period of experimental venous hypertension produced by means of standing. Assay of VEGF protein was performed with a sandwich enzyme-linked immunosorbent assay. Plasma VEGF level was elevated in both groups of patients with venous disease compared with the control group. The median VEGF levels among patients were 81 pg/mL (interquartile range [IQR] 56 to 122) supine and 98 pg/mL (IQR 63 to 153) after standing for 30 minutes. Median VEGF levels among control subjects were 52 pg/mL (IQR 35 to 71) lying supine and 60 pg/mL (IQR 39 to 105) after standing for 30 minutes. Experimental venous hypertension caused a small rise in VEGF levels among the patients but not the control subjects. Further studies are required to determine whether increased VEGF expression contributes to tissue injury in chronic venous disease.

Adult↗
PubMed1998

Endothelial activation in patients with chronic venous disease.

OBJECTIVES: Leukocyte trapping due to leukocyte-endothelial activation has been implicated as the cause of lipodermatosclerosis and ulceration in patients with chronic venous disease. We investigated endothelial activity in normal controls and patients subjected to short-term venous hypertension. METHODS: Twenty-five normal volunteers and 30 patients with chronic venous disease divided into two groups: varicose veins with skin changes (LDS, n = 15); and varicose veins without skin changes (VVs, n = 15) were studied. Blood samples were taken from a foot vein before and after experimental venous hypertension. Plasma levels of ELAM-1 (endothelial leukocyte adhesion molecule-1), ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and von Willebrand factor (vWf) was measured by an ELISA. RESULTS: There was a significant rise in the plasma concentration of ELAM-1, ICAM-1 and VCAM-1 in patients and normal controls in response to venous hypertension. Basal levels of plasma VCAM-1 and vWf were higher in patients with LDS compared to patients with VVs. The magnitude of rise of VCAM-1 was greater in patients with LDS compared to patients with VVs (p = 0.01, Mann-Whitney U-test). There was no difference in the basal levels or in the magnitude of change in plasma ICAM-1 and ELAM-1 between the two patient groups. CONCLUSION: Venous hypertension results in endothelial activation which may aid endothelial-leukocyte adhesion. Patients with LDS exhibit increased VCAM-1, which is a counterligand for receptors expressed by monocytes and lymphocytes signifying that these cells may be more important in the development of skin changes.

Adult↗
PubMed1998

Variable venous anatomy of the popliteal fossa demonstrated by duplex scanning.

BACKGROUND: Location of the sapheno-popliteal junction (SPJ) is highly variable and therefore often difficult to identify correctly at operation. The anatomy is often complicated by associated pathology in the popliteal fossa, which makes clinical examination unreliable. OBJECTIVE: The purpose of our study was to quantify this variability and record other concomitant pathology in patients with sapheno-popliteal junction incompetence. METHODS: We retrospectively reviewed duplex scans of 544 patients with 638 legs showing SPJ incompetence, from a total of approximately 4000 patients attending our laboratory between August 1993 and August 1995. RESULTS: We found that 51% of sapheno-popliteal junctions were located within 2 cm above the popliteal skin crease and a further 36% within 4 cm, with the remaining situated anywhere between 4 and 10 cm above the popliteal skin crease. Additionally 18% of patients had either Giacomini or gastrocnemius vein incompetence in addition to SPJ incompetence, further complicating the clinical picture. CONCLUSION: When SPJ incompetence is suspected, duplex scanning identifies the exact location of the junction and other associated pathology in the popliteal fossa, and allows the position of the junction to be marked on the leg preoperatively.

Anatomy, Cross-Sectional↗
PubMed1997

Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication.

BACKGROUND: Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-0:3, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls. METHODS AND RESULTS: Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of > or = 30 and < or = 300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P < .01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo; median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P < .01, Mann-Whitney test). Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted. CONCLUSIONS: These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted.

Aged↗
PubMed1997

Leukocyte activity in the microcirculation of the leg in patients with chronic venous disease.

PURPOSE: It has been suggested that leukocyte trapping and activation in the microcirculation of the leg skin causes lipodermatosclerosis and ulceration in patients with chronic venous disease. Ambulatory venous hypertension is accepted as the physiologic factor that leads to ulceration. We investigated leukocyte endothelial adhesion in patients who were subjected to short-term venous hypertension. METHODS: Two groups of patients with venous disease were studied: group 1, varicose veins with skin changes (n = 15); and group 2, varicose veins without skin changes (n = 15). Blood samples were taken from a foot vein before and after standing for 30 minutes to raise the venous pressure in the lower limb, and after lying supine again for 10 minutes. The samples were analyzed for leukocyte surface CD11b and L-selectin (CD62L) expression using a flow cytometer. Plasma-soluble L-selectin was also measured using an enzyme-linked immunosorbent assay. RESULTS: In patients with skin changes, median neutrophil CD11b levels fell from 4.66 to 3.83 arbitrary units (p = 0.005, Wilcoxon) after 30 minutes of venous hypertension, Median monocyte CD11b levels fell from 7.65 to 5.8 arbitrary units (p = NS, Wilcoxon) after venous hypertension and then fell further to 5.43 arbitrary units (p = 0.02 vs baseline; Wilcoxon) when the venous hypertension was removed. Neutrophil and monocyte L-selectin levels also fell in response to venous hypertension, remaining low even after venous hypertension was removed. A similar pattern was seen in patients with uncomplicated varicose veins. There was a rise in soluble L-selectin in the plasma of both groups of patients after venous hypertension, reflecting leukocyte adhesion to endothelium. In the group of patients with skin changes the level of soluble L-selectin rose from 695 ng/ml to 836 ng/ml (p = 0.02, Wilcoxon), and in the group without skin changes the rise was from 700 ng/ml to 801 ng/ml (p = 0.02, Wilcoxon). CONCLUSION: Venous hypertension results in sequestration of the more activated population of neutrophils and monocytes in the microcirculation of the leg in patients with venous disease. These cells bind to the endothelium, releasing L-selectin, and do not emerge from the limb when venous hypertension is reversed. These findings do not differ between patients with varicose veins and those with skin changes.

Adult↗
PubMed1996

Leukocyte migration in the leg in response to experimental venous hypertension.

PURPOSE: Leukocyte trapping and activation in the microcirculation of the legs may play an important role in causing skin damage in venous disease. Leukocyte emigration from the microcirculation and subsequent locomotion in response to venous hypertension was studied in a group of 12 normal volunteers using a "skin window" technique. METHODS: Two 0.5-cm square dermal abrasions were made with a dental stone over the gaiter area of the leg and the flexor aspect of the forearm (control), which were covered with moist micropore membranes. The volunteers lay supine for 30 minutes, and then stood supported for 30 minutes to raise the venous pressure in the leg, and then lay supine again for 30 minutes. The experiment was repeated in six volunteers who lay supine for the whole period. The membranes were changed and collected every 15 minutes, fixed in formal saline solution, and dual-stained for monocytes and polymorphonuclear leukocytes. The type and numbers of cells that emigrated and the furthest distance traveled (leading front) by the cells through the membrane were measured. RESULTS: Both in arms and legs, the vast majority of cells that emigrated were neutrophils, with very few monocytes (arm, 93% neutrophils and 7% monocytes; leg, 97% neutrophils and 3% monocytes). In the 30 minutes after venous hypertension, leukocyte migration significantly decreased in the leg (median leukocyte locomotion: basal, 75.3 microns; standing, 73.5 microns; after hypertension, 62.9 microns; p = 0.012, Wilcoxon matched pairs signed rank test), but not in the arm (basal, 86.2 microns; standing, 84.4 microns; after hypertension, 85.5 microns; p = NS) or when the experiment was repeated with the volunteers lying supine for the entire period (basal, 91.5 microns; standing, 89.4 microns; after hypertension, 92.6 microns; p = NS). CONCLUSIONS: Leukocyte migration is decreased immediately after experimental venous hypertension, which may be a result of the release of factors that inhibit migration.

Adult↗
PubMed1995

Effects of compression and type of bed surface on the microcirculation of the heel.

OBJECTIVE: To assess the effects of compression on the skin microcirculation of the heel using laser Doppler fluxmetry. DESIGN: Parallel groups comparing patients with control groups. SETTING: Department of Surgery, University College London Medical School, London. SUBJECTS AND MATERIALS: Ten patients at risk of developing pressure ulceration, 10 age- and sex-matched healthy subjects and 10 young, healthy volunteers. An acrylic indenter with a slot to accommodate a laser Doppler probe was used to apply compression to the heel region. A pressure sensor was used to measure the applied compression. OUTCOME MEASURES: The resting laser Doppler flux was measured with the subject lying supine. Compression forces were then applied in increments from 50 g to 1500 g and the corresponding interface pressure (IP) and laser Doppler flux (LDF) recorded. The IP and LDF were also measured from the heel while the subject was lying on a low air-loss system and then on an NHS conventional hospital bed. RESULTS: The resting LDF is lower in the patient group compared to the control groups (p < 0.05). Compression of the heel caused a progressive decrease in LDF in all groups. Compression greater than 50 mmHg as well as lying on an NHS bed reduced the LDF signal to a minimal value (biological zero). On the low air-loss system, the median LDF was 17% of the resting value in the age-matched control group and 32% in the patient group. CONCLUSIONS: The results indicate that the heel microcirculation is vulnerable to compression. The low air-loss system maintained the IP sufficiently low to prevent complete cessation of the heel microcirculation.

Adult↗
PubMed1994

Saphenous vein reflux without incompetence at the saphenofemoral junction.

Duplex ultrasonography was used to assess patients with primary varicose veins to determine whether varicosities of the long saphenous vein (LSV) occurred without saphenofemoral junction (SFJ) incompetence. Some 167 consecutive patients with the clinical diagnosis of primary varicose veins were investigated. Of 190 limbs with LSV reflux 63 had no SFJ incompetence, of which only five had incompetent perforators; these were midthigh perforators in two limbs and medial calf perforators in three. LSV reflux often occurs in the presence of a competent SFJ. This indicates that, in such circumstances, saphenofemoral ligation alone is unlikely to control varices associated with LSV reflux. It also suggests that the development of primary varicose veins may be an ascending rather than a descending phenomenon.

Adult↗
PubMed1994

Stripping of the long saphenous vein in the treatment of primary varicose veins.

Eighty-nine legs with long saphenous vein (LSV) reflux and saphenofemoral junction incompetence were treated by saphenofemoral ligation and multiple avulsions; patients were randomized to undergo additional stripping of the LSV from groin to upper calf (n = 43) or no additional treatment (n = 46). At a median of 21 months after surgery recurrence was evaluated by duplex ultrasonography, photoplethysmography, clinical examination and patient assessment. Fewer persisting incompetent LSVs in the calf were found (21 versus 38) and median (interquartile range) photoplethysmographic refilling times were longer (20 (13-27) versus 14 (11-21) s) when the LSV was stripped than after saphenofemoral ligation alone (both P < 0.1). More patients were completely satisfied (65 versus 37 percent and were recurrence-free (65 versus 17 per cent) when the LSV had been stripped compared with saphenofemoral ligation alone (P < 0.05 and P < 0.001 respectively). The addition of LSV stripping to saphenofemoral ligation and multiple avulsions results in a better overall outcome.

Adult↗
PubMed1994

Plasma elastase in venous disease.

The plasma elastase level was measured as a marker of neutrophil degranulation in three groups, each of 15 patients, with uncomplicated varicose veins, lipodermatosclerosis (LDS) and venous ulceration. The values obtained were compared with those in age- and sex-matched control subjects. Significantly higher levels of elastase were found in all patient groups compared with controls: median 25.6 ng/ml for patients with uncomplicated varicose veins, 22.1 ng/ml for those with LDS, 26.0 ng/ml for those with venous ulceration. There was no difference in neutrophil count between the patient and control groups. These results provide evidence of increased neutrophil degranulation in patients with venous disease. The finding of raised elastase levels in all three patient groups shows that this was not due solely to the inflammatory process characterizing LDS and venous ulceration.

Adult↗
PubMed1994

Duplex ultrasonography for assessment of venous valvular function of the lower limb.

Both legs of 29 patients with venous disease and those of 15 controls without venous disease were assessed by duplex ultrasonography. The duration of reverse flow after release of manual calf compression was measured in the common femoral, long saphenous, popliteal and short saphenous veins. Before undertaking the study, the reproducibility of the technique was evaluated in six subjects by repeating the examination over 3 consecutive days; the coefficient of variation of the test was 7.3 per cent. The 95 per cent confidence interval (c.i.) of the median (0.16 s) of all measurements in the normal limbs was 0.12-0.18 s. The 95 per cent c.i. for the 95th percentile of all measurements in normal limbs was 0.32-0.52 s. In limbs with clinical evidence of venous disease at least one of the sites examined was found to have reverse flow lasting longer than 0.5 s. These data suggest that the measurement of reverse flow after release of manual calf compression is a reproducible technique. While the method records some reverse flow in normal veins, its duration is unlikely to exceed 0.5 s; significant reflux is therefore defined as reverse flow exceeding 0.5 s.

Adult↗
PubMed1994

Interstitial laser photocoagulation as a treatment for breast cancer.

This preliminary report describes the use of interstitial laser photocoagulation to manage small breast cancers. Forty-four patients were treated with a diode laser of 805 nm under local anaesthesia in the interval between diagnosis and surgery. Ultrasonography was used in 42 patients and computed tomography (CT) in two to place the fibre in the tumour and monitor laser effects. Laser-induced necrosis within the resected tumour varied from 0 to 25 mm in diameter. The presence of charring in the tumour around the fibre tip after treatment was associated with significantly larger diameters of necrosis than when charring did not occur (median 13 versus 6 mm, P = 0.002). Precharring the fibre resulted in a more predictable diameter of necrosis (median 14 mm). Ultrasonography was inaccurate in assessing laser damage; dynamic CT and magnetic resonance imaging may be of more use. Interstitial laser photocoagulation is simple and safe, and can produce necrosis of a reasonably predictable extent.

Breast↗
PubMed1994

Effect of leg elevation on the skin microcirculation in chronic venous insufficiency.

PURPOSE: Leg elevation is advised in the treatment of venous disease associated with edema. We have used laser Doppler fluxmetry to assess the effects of leg elevation on the skin microcirculation. METHODS: Fifteen patients with lipodermatosclerosis caused by chronic venous insufficiency and 15 control subjects were studied. Measurements were made from the liposclerotic skin of patients and 8 cm above the medial malleolus in control subjects. Laser Doppler flux, blood cell velocity, and concentration of moving blood cells were recorded with the subject lying in the supine position and after elevating the foot 30 cm above the heart level. RESULTS: In subjects in the horizontal position, the resting laser Doppler flux was significantly higher in patients with lipodermatosclerosis than in control subjects (median difference 63 arbitrary units; 95% confidence interval: 36, 108). This difference was due to a higher concentration of moving blood cells in the patient group (median difference 6.5 arbitrary units; 95% confidence interval: 3.4, 9). The blood cell velocity was not statistically significant between the two groups. On leg elevation, there was a substantial increase in the laser Doppler flux in the patient group; the median percentage increase in flux was 45% (p < 0.01). This was due to an increase in blood cell velocity; the median percentage increase was 41% (p < 0.01). There was no corresponding change in the concentration of moving blood cells. The results in the control group showed a similar trend but have not reached statistical significance. CONCLUSION: We conclude that limb elevation enhanced the microcirculatory flow velocity in liposclerotic skin of patients with chronic venous insufficiency.

Aged↗
PubMed1994

Microangiopathy of the skin and the effect of leg compression in patients with chronic venous insufficiency.

PURPOSE: The reasons for the efficacy of leg compression in the treatment of chronic venous insufficiency are not clear. We have used laser Doppler fluxmetry to assess the effect of external compression on the skin microcirculation. METHODS: Fifteen patients with lipodermatosclerosis caused by chronic venous insufficiency and 15 control subjects were studied in the supine and sitting positions. The laser Doppler probe, incorporated in a polyethylene chamber, was applied to the lower leg underneath a blood pressure cuff. Pressures were applied from 10 to 100 mm Hg in increments of 10 mm Hg. A computer data logging system recorded laser Doppler flux blood cell velocity, and concentration of moving blood cells. RESULTS: In patients in the supine position, 20 mm Hg compression resulted in a median increase of 33% in laser Doppler flux, and a median increase of 79% in blood cell velocity, but higher pressures caused a progressive decrease in laser Doppler flux and blood cell velocity. With the patient in the sitting position, compression up to 60 mm Hg caused an increase in laser Doppler flux (median percentage increase at 20 mm Hg compression 84%) and blood cell velocity (median percentage increase at 20 mm Hg compression 22%). At 20 mm Hg compression, the concentration of moving blood cells decreased in the supine position (median percentage fall 27%) but did not change significantly in the dependent position. The effects of compression in control subjects were similar to those in patients, but to a lesser degree. CONCLUSION: Our study suggests that compression treatment may achieve part of its effect by causing an increase in the microcirculatory flow velocity.

Aged↗
PubMed1994

Treatment of the critically ischaemic lower limb.

Medical therapy of PAOD is only indicated in patients unsuitable for vascular reconstruction or angioplasty. The approach includes early detection of subjects at risk, avoidance of known risk factors, and appropriate management of diseases such as diabetes and hypertension. Vasodilators are of little use orally, though some drugs may have a part to play for short-term management and iloprost should be considered for patients unsuitable for revascularization. The ankle systolic or toe pressure should be used as a measure of disease and, if reduced, arteriography should be performed. This should not be limited to those thought fit for major surgery, as angioplasty or thrombolytic therapy may be appropriate, and aortoiliac disease may be treated by extra-anatomic bypass if not suitable for major surgery. Arterial reconstruction is associated with a reduction in both mortality and amputation, and should be attempted if a greater than 25% chance of limb salvage could be expected.

Acute Disease↗