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Biomedical subjects

M K O'Malley

Publications and source records attributed to M K O'Malley.

At least 19 recordsLinked to original sources
PubMed1992

Colour-coded duplex ultrasonography in the selection of patients for endovascular surgery.

Endovascular surgery using angioplasty or atherectomy may potentially relieve the symptoms of claudicants with minimal morbidity, but results are best when short stenoses are treated. In this study, colour-coded duplex ultrasonography has been compared with angiography. In aortoiliac segments duplex examination had a sensitivity of 88 per cent and a specificity of 100 per cent; in femoropopliteal disease the sensitivity was 100 per cent and duplex scanning identified more disease than angiography. Subsequently, 73 symptomatic limbs with femoropopliteal disease were scanned to assess their suitability for endovascular surgery. Of these limbs, 27 (37 per cent) had suitable lesions and the remaining 46 (63 per cent) were spared angiography. Colour-coded duplex ultrasonography can reliably be used to select patients for endovascular surgery.

Aorta, Abdominal↗
PubMed1992

Serotonin-induced contractility in human saphenous vein is inhibited by naftidrofuryl.

Vascular endothelial denudation contributes to vasospasm by causing platelet aggregation and the subsequent release of vasoconstrictors such as serotonin. It has recently been suggested that naftidrofuryl fumarate (NFT) may oppose serotonin-induced vasoconstriction. Fourteen rings of human saphenous vein from 14 patients undergoing varicose vein surgery were tested in standard organ bath experiments. Cumulative dose-response curves and maximal contraction in response to serotonin were recorded and this was repeated in the presence of NFT at 10(-6) and 10(-3) mol/l. The difference in maximal contractility between the three sets of curves was significant (P < 0.0001). Sensitivity to serotonin in each of the three curves was measured using the concentration for half-maximal response; differences were again significant (P < 0.0001). It is concluded that NFT reduces serotonin-induced contractility in a dose-dependent fashion in rings of human saphenous vein in vitro. These results suggest a possible role for NFT in reducing vasospasm and support further investigation of this drug.

Dose-Response Relationship, Drug↗
PubMed1992

Long-term reduction of intimal hyperplasia by the selective alpha-1 adrenergic antagonist doxazosin.

Studies have shown that alpha 1-adrenergic blockade reduces intimal hyperplasia in the rabbit aorta. In this study a selective alpha 1-adrenergic antagonist, doxazosin, has been used to examine whether this effect is persistent and dose dependent. Forty-eight New Zealand White rabbits underwent endothelial denudation of the abdominal aorta using a Fogarty balloon catheter. Test rabbits were given low-dose (2 mg) or high-dose (8 mg) doxazosin daily and all animals killed at either 1 or 12 weeks after the procedure. The aortas were harvested after fixation in situ with 4 per cent glutaraldehyde and neointimal hyperplasia was measured, using an x-y digitizer, as the percentage reduction in luminal cross-sectional area. At 1 week after surgery, rabbits receiving the low dose had a median area reduction of 7.7 per cent and those receiving the high dose a reduction of 8.2 per cent; both had significantly less intimal hyperplasia than control rabbits, which had a median area reduction of 14.8 per cent (P < 0.01). However, at 12 weeks, when compared with the 32.6 per cent reduction in the control group, only those rabbits receiving high-dose doxazosin had significantly less intimal hyperplasia, with a reduction of 5.5 per cent (P < 0.001). It is concluded that selective alpha 1-adrenergic blockade significantly reduces neointimal hyperplasia, that this effect is dose dependent, and that it persists for at least 3 months.

Animals↗
PubMed1992

The reproducibility of colour-coded duplex scanning in measuring arterial wall dimensions.

Intimal hyperplasia continues to be a major problem following vascular surgery but experimental evidence suggests that it can be reduced pharmacologically. For clinical studies an accurate, reproducible and non-invasive image of the intima and lumen is required. We have assessed the value of the Acuson 128 Colour Duplex for such studies. Ten patients had their common femoral arteries scanned at a fixed point by two experienced observers on two separate occasions. External vessel diameter, luminal diameter and internal diameter (i.e. the diameter within the internal elastic lamina) were measured in both longitudinal and cross-sectional views. Cross-sectional area and degree of stenosis were all measured and all parameters expressed as limits of agreement. The mean external diameter of the common femoral arteries was 10.5 +/- 1.6 mm. Measurements in the longitudinal view were highly reproducible with limits of agreement ranging from -0.67 - +0.25 mm (internal diameter) to -1.49 - +1.31 mm (luminal diameter). In order to detect a meaningful change in longitudinal external diameter a real difference of 0.86 mm is required representing a change of less than 10%. Cross-sectional diameter measurements were similarly reproducible (-0.73 - +0.47 mm to -1.97 - +1.79 mm). However, cross-sectional area measurements had a wide variation so that the error in degree of stenosis was -25.4 - +30.2%. Thus, duplex ultrasound reproducibly images the layers of the arterial wall. Prospective studies of intimal hyperplasia are feasible but must be based on longitudinal and cross-sectional diameters rather than cross-sectional areas.

Aged↗
PubMed1991

Infrainguinal polytetrafluoroethylene grafts: saved limbs or wasted effort? A report on ten years' experience.

Two-hundred and twenty-four infrainguinal polytetrafluoroethylene reconstructions were performed for critical ischemia over a 10 year period: 48 to the above-knee popliteal artery, 113 to the below-knee popliteal artery, and 63 to the tibial vessels. The cumulative patency rates were 84 +/- 6% and 63 +/- 9% for above-knee popliteal, 53 +/- 5% and 35 +/- 7% for below-knee popliteal, 45 +/- 6% and 30 +/- 9% for tibial vessels at one and five years respectively. Limb salvage rates were 81 +/- 6% and 73 +/- 9% (above-knee popliteal), 69 +/- 5% and 57 +/- 9% (below-knee popliteal), 64 +/- 7% and 32 +/- 10% (tibial vessels) at one and five years respectively. Graft occlusion did not result in limb loss in 32 cases. Preoperatively, 54% of the patients had limited mobility while 43% were regarded as severely restricted. At follow-up, 57% of the patients were considered to be independent, 26% had limited mobility, and 17% were still severely restricted. Polytetrafluoroethylene provides good short-term limb salvage and improved mobility in patients with critical ischemia and poor life expectancy. Its use is well worth the effort.

Activities of Daily Living↗
PubMed1991

Non-specific abdominal pain in pre-menopausal women.

Non-specific abdominal pain (NSAP) is a well-recognized clinical problem which places a significant burden on health resources. We studied 100 premenopausal women who were admitted consecutively through the Accident and Emergency Department of the Mater Misericordiae Hospital to assess final diagnosis, duration of hospital stay, extent of investigation, recurrence of symptoms and final diagnosis. The patients were placed in the following diagnostic categories: Gynaecological (30%), Renal (9%), Acute appendicitis (23%), Miscellaneous (9%) and Non-specific abdominal pain which accounted for 29% of the admissions. The mean duration of hospital stay for patients with NSAP was 67 days, one third underwent specialized investigations and one third underwent appendicectomies for normal appendices. On review, one year after admission, 66% of patients admitted with NSAP were asymptomatic.

Abdominal Pain↗
PubMed1991

Altered catecholamine receptor affinity in rabbit aortic intimal hyperplasia.

Intimal thickening is a universal response to endothelial denudation and is also thought to be a precursor of atherosclerosis. We have demonstrated selective supersensitivity in arterial intimal hyperplasia to norepinephrine and we now report a possible mechanism for this. Binding studies in rabbit aorta with the selective alpha 1-adrenergic radioligand 125I-HEAT demonstrated that there was no change in receptor density (20 +/- 4 fmole/10(6) cells) in intact vascular smooth muscle cells at either 5 or 14 days after denudation. However, competition studies showed a 2.6-fold increase in alpha 1-adrenergic receptor affinity for norepinephrine in intimal hyperplastic tissue (P less than 0.05). This increased affinity for norepinephrine was associated with a greater increase in 32P-labeled phosphatidylinositol (148% intimal thickening versus 76% control) and phosphatidic acid (151% intimal thickening versus 56% control) following norepinephrine stimulation of free floating rings of intimal hyperplastic aorta. These data suggest that the catecholamine supersensitivity in rabbit aortic intimal hyperplasia is receptor mediated and may be linked to the phosphatidylinositol cycle.

Animals↗
PubMed1990

A new technique for bilateral iliac vein and inferior vena cava reconstruction using reinforced polytetrafluoroethylene.

We report on the management of a patient with intractable venous claudication and ulceration due to bilateral iliac vein and inferior vena cava occlusion. An inverted V graft was constructed from two 8 mm diameter reinforced PTFE grafts. The upper end was anastomosed to the inferior infrarenal vena cava and the lower ends anastomosed to the common femoral veins. Bilateral arteriovenous fistulas were fashioned. Nine months later the graft is patent and the patient's only symptom is mild ankle edema. The theoretical advantage of this type of graft is that occlusion of one limb will not compromise the other, thus leaving a number of secondary options open if this should happen.

Aged↗
PubMed1990

"Haemorrhagic" carotid plaque does not contain haemorrhage.

The presence of haemorrhage in carotid bifurcation atheromatous plaques is widely believed to be associated with the production of ischaemic neurological events. This study set out to characterise plaque composition in symptomatic (SYM) and asymptomatic (ASYM) patients and to identify, if possible, the origin of intra-plaque haemorrhage. Fifty-nine plaques (50 SYM and 9 ASYM) were serially sectioned and examined for haemorrhage, haemosiderin, fibrin, cholesterol and collagen. Immunoperoxidase and electron microscopy studies were carried out on sections from five plaques in order to identify blood breakdown products. Intra-plaque haemorrhage was identified in 40 (68%) plaques and was similar in SYM and ASYM plaques. In only one did it constitute more than 15% of plaque content, and in the remainder it consisted of small collections of erythrocytes constituting greater than 1% of plaque content in only 21 (35%) plaques. The predominant non-fibrous component was a pink amorphous material mixed with cholesterol. Apart from traces of platelet breakdown products there was no evidence of haemorrhage in this pink material. Plaque roof rupture or ulceration was seen in 39 (66%) and in almost all cases overlay the amorphous/cholesterol material. Blood vessels were identified in 51 87%) plaques but were in close proximity to haemorrhage in only nine (15%).

Arteriosclerosis↗
PubMed1989

Role for prazosin in reducing the development of rabbit intimal hyperplasia after endothelial denudation.

Intimal hyperplasia is the universal response to endothelial denudation and occurs after a variety of vascular procedures. In a proportion of cases the smooth muscle cell proliferation may lead to stenosis of the blood vessels. These vessels exhibit increased sensitivity to noradrenaline that can be reduced by the alpha 1-adrenergic antagonist prazosin. Because the alpha 1-adrenergic receptor and platelet-derived growth factor (which promotes vascular smooth muscle cell proliferation) act through the same metabolic pathway, it was postulated that alpha 1-adrenergic blockade might reduce the development of intimal hyperplasia. Twenty-eight New Zealand White rabbits underwent endothelial denudation of the aorta using a Fogarty balloon catheter. Test rabbits were treated with prazosin from the day of operation until they were killed. All rabbits were killed either 1 or 4 weeks after endothelial denudation. Intimal hyperplasia in cross-sections of the aorta was measured using an X-Y digitizer and was standardized in terms of percentage luminal reduction. Prazosin-treated rabbits had significantly less luminal reduction at 1 week (0.75(1.8) versus 9.7(3.1) per cent, mean (s.d.), P less than 0.001) and at 4 weeks (14.7(4.4) versus 25.3(12.8) per cent, P less than 0.05) than control rabbits. It is concluded that prazosin caused a major reduction in the development of intimal hyperplasia.

Animals↗
PubMed1988

A neutrophil derived factor(s) stimulates [3H]thymidine incorporation by vascular smooth muscle cells in vitro.

There is increasing evidence for the involvement of inflammatory cells in the development of intimal hyperplasia. This study examines the effect of human neutrophils on the incorporation of [3H]-thymidine into acid precipitable materials (DNA) in cultured rabbit vascular smooth muscle cells. Co-culture of intact neutrophils and vascular smooth muscle cells caused [3H]-thymidine incorporation by these cells to increase 209 +/- 22% (mean +/- SEM) of control. Sonication of the neutrophils abolished this effect (117 +/- 10%). Neutrophil conditioned medium prepared in the presence or absence of fetal calf serum had a similar effect on [3H]-thymidine incorporation by vascular smooth muscle cells (204 +/- 20% and 172 +/- 17% respectively). Stimulation of neutrophils with either Concanavalin A or serum-activated zymosan failed to increase production of the factor(s). The neutrophil derived factor(s) prepared in minimal essential medium was partially stable at 56 degrees C, but inactivated by boiling. Dialysis (pore size 12,000-14,000) did not remove the factor(s). Cyclooxygenase inhibition with indomethacin did not inhibit production of the factor(s) by neutrophils, but indomethacin caused an increase in [3H]-thymidine incorporation by vascular smooth muscle cells (181 +/- 11%). Indomethacin together with intact neutrophils had an additive effect on [3H]-thymidine incorporation (273 +/- 42%) into cellular DNA. These data show that neutrophils produce a factor(s) that stimulates [3H]-thymidine incorporation into DNA by vascular smooth muscle cells and suggests that vascular smooth muscle proliferation and intimal hyperplasia may be initiated by neutrophils adherent to sites of endothelial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Association of polymorphonuclear leukocytes with sites of aortic catheter-induced injury in rabbits.

The kinetics of the association of polymorphonuclear leukocytes (PMNs) with arterial balloon catheter-induced injury have been examined. An average of 6 X 10(7) PMNs were isolated from 20 ml of blood and labelled with 111In-oxine for reinfusion into the donor rabbit. The cells remained viable as demonstrated by both in vitro and in vivo tests of cell function. The abdominal aorta of rabbits was denuded of endothelium and immediately, 24 h, or 5 weeks later, exposed to autologous radiolabelled PMNs for 1 h. The presence of PMNs at sites of denudation was demonstrated by detection of the radioactive label and was confirmed by light and electron microscopy after 24 h, but not at 5 weeks. Immediately following denudation radioactivity was 2.44 +/- 0.33 times control (P = 0.006); 2.52 +/- 0.18 at 24 h (P = 0.005); and 1.88 +/- 0.32 times control at 5 weeks (P = 0.045). The presence of PMNs, or their products, 5 weeks after denudation suggests a more complex role of PMNs and possibly a direct involvement in the long term changes resulting from arterial balloon catheter injury.

Animals↗
PubMed1987

Norepinephrine-induced vasoconstriction is increased in intimal hyperplastic arteries of the dog.

Norepinephrine-induced arterial contraction in vitro is known to be increased after endothelial denudation and during the subsequent development of intimal hyperplasia. We now report the response to norepinephrine in intimal-thickened iliac vessels in conscious dogs. Seven dogs underwent balloon catheter deendothelialization of the right iliac artery. Three weeks later, ultrasonic transducers were implanted on both iliac arteries to record dynamic vessel dimension. A catheter was inserted into the terminal abdominal aorta for drug infusion and blood pressure monitoring. The dogs were studied unsedated 2 days after instrumentation. Norepinephrine was infused at doses that did not affect blood pressure (0.01 to 0.05 micrograms/kg/min). Control vessel diameter decreased from 5.2 mm +/- 0.3 to 5.1 mm +/- 0.3 (2.4% +/- 1.0% when standardized to baseline diameter) and intimal hyperplastic vessels from 6.2 mm +/- 0.4 to 5.7 mm +/- 0.4 (7.6% +/- 1.7%). The difference between control and intimal hyperplastic vessel vasoconstriction was significant at p less than 0.0025. The calculated reduction in total vessel cross-section area for control vessels was 4.5% +/- 1.9%. In intimal hyperplastic vessels total cross-sectional area was reduced by 14.5% +/- 3.3% by vasoconstriction and the luminal cross-sectional area was reduced by 17.9% +/- 0.7% by the intimal hyperplasia. These data suggest that luminal compromise due to intimal hyperplasia is compounded by increased sensitivity to norepinephrine. This effect, demonstrated in a large elastic artery shortly after endothelial denudation, may be of even greater significance in a smaller vessel with advanced intimal hyperplasia.

Animals↗