Biomedical subjects

J A Dormandy

Publications and source records attributed to J A Dormandy.

At least 19 recordsLinked to original sources

PubMed1999

The association between laser Doppler reactive hyperaemia curves and the distribution of peripheral arterial disease.

OBJECTIVES: To determine whether postocclusive laser Doppler fluxmetry (LDF) curves can be related to the arteriographic distribution of disease. DESIGN: Prospective study. MATERIALS: Sixty-nine patients with symptomatic peripheral ischaemia and 15 healthy subjects. METHODS: Laser Doppler fluxmetry (LDF) was monitored on the dorsum of the symptomatic foot following 2 min of arterial occlusion at the ankle. During reperfusion three patterns of LDF were identified (types I-III). All patients subsequently underwent arteriography which was reported independent of LDF results. The distribution of disease, particularly patency of below-knee vessels, was related to the type of LDF curve observed during reactive hyperaemia. RESULTS: Type I curves were observed in all healthy subjects and 75% of patients with a single arterial lesion. Type II curves were found in 78% of patients with multiple lesions above the knee. The presence of either a type I or II curve was associated with a continuous vessel from knee to ankle (positive predictive value 83%, p < 0.01), whilst type III curve was associated with discontinuous infrapopliteal run-off (positive predictive value 86%, p < 0.01). CONCLUSIONS: This pilot study suggests that post-occlusive LDF curves may identify the distribution of arterial disease and may be useful in the non-invasive management of peripheral ischaemia.

Chi-Square Distribution↗

PubMed1998

Rationale for antiplatelet therapy in patients with atherothrombotic disease.

The most common cause of morbidity and mortality in developed countries results from atherosclerosis and superimposed thrombosis (atherothrombosis) leading to partial or complete vascular occlusion. Much evidence supports the idea that all atherothrombosis is similar, regardless of which vascular bed it occurs in. Thus, similar therapies may be used for patients with symptomatic cardiac, cerebral, or peripheral vascular disease. The types of agents that have shown efficacy in atherothrombosis include antihypertensives, lipid-lowering agents and antiplatelet agents. The focus of this article is on the antiplatelet agents, of which there are several subcategories, including ADP receptor antagonists, GpIIb/IIIa antagonists, cyclo-oxygenase inhibitors and prostacyclin analogues. Clinical testing of these agents is ongoing and the efficacy and safety of the various agents are being defined. To date, the ADP receptor antagonist, clopidogrel, appears to provide the best antithrombotic result with the fewest side effects. Further testing may reveal that combinations of the various forms of antiplatelet agents may provide even further improvements on safety and efficacy.

Arteriosclerosis↗

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

The predictive value of laser Doppler fluxmetry and transcutaneous oximetry for clinical outcome in patients undergoing revascularisation for severe leg ischaemia.

OBJECTIVES: To investigate the predictive value of laser Doppler fluxmetry and transcutaneous oximetry in 41 patients undergoing technically successful revascularisation for severe leg ischaemia. DESIGN: Toe and ankle systolic arterial pressures, transcutaneous oxygen tension (tcpO2), and stressed laser Doppler fluxmetry at the foot (time to peak laser Doppler flux following 2 min arterial occlusion, tp LDF, and the response of LDF to raising the leg 40 cm, the elevated:supine LDF ratio) were measured before revascularisation. Six months later these measurements were compared in those patients who were clinically improved, and those who still had symptoms of severe ischaemia or had lost their limb. SETTING: Vascular Laboratory, St. George's Hospital, London SW17, U.K. RESULTS: Six months following revascularisation 30 (73%) of the 41 patients had partial or complete symptomatic relief. Six (15%) had undergone major amputation and five (12%) still had symptoms of severe ischaemia. Before intervention toe and ankle systolic pressures were similar in the 30 who were improved and the 11 who had lost, or were still at risk of losing, their leg. Pre-revascularisation tcpO2 was significantly lower (18.3 mm Hg vs 33.5 mm Hg; p < 0.05) and tp LDF significantly longer (140 s vs 92 s; P < 0.05) in the 11 patients who were not clinically improved at 6 months. Whilst pre-revascularisation toe and ankle pressures below 30 mm Hg and 50 mm Hg respectively identified only 55% of those patients who were not improved 6 months later, a tp LDF in excess of 100 s identified 82% (p < 0.05) and was noted in five of the six amputees. CONCLUSION: Microcirculatory assessments performed in patients with limb-threatening ischaemia are likely to be more deranged in those patients who suffer clinical failure or amputation despite an apparently successful revascularisation procedure.

Amputation, Surgical↗

PubMed1997

Hypercoagulable abnormalities and postoperative failure of arterial reconstruction.

OBJECTIVES: To determine whether preoperative hypercoagulable abnormalities are independent risk-factors for the failure of arterial reconstruction in leg ischaemia. METHODS: Sixty consecutive patients were studied before, and for 1 year following, elective peripheral revascularisation. Antithrombin III, protein C and protein S levels, and tests for lupus anticoagulant were performed preoperatively, and then repeated on the first and third postoperative days and after 1 and 6 months. Heparin-associated thrombocytopenia was also investigated if there was a postoperative fall in platelet count greater than 100 x 10(9)/l. RESULTS: Forty-six (77%) procedures were performed for critical ischaemia and 15 (25%) involved infrapopliteal reconstruction. The nature of surgery or accepted risk factors for occlusion were comparable between the 40 (67%) patients with patent reconstructions at 1 year and the 20 (33%) who had suffered failure. Preoperative hypercoagulable abnormalities were detected in 21 (35%) patients, with a three times greater incidence in those whose reconstructions failed (65% vs. 20%, p < 0.01), and in 11 of 12 patients suffering early (within 1 month) occlusion. The lupus anticoagulant was more frequently detected when prosthetic grafts were already present (p < 0.05) and carried a positive predictive value for reocclusion of 67% (p < 0.01). All three postoperative deaths occurred in patients with low protein S levels before surgery. CONCLUSIONS: Hypercoagulable abnormalities are common prior to arterial revascularisation and are independently associated with subsequent failure.

Adult↗

PubMed1997

The relationship between the delayed improvement in ankle-brachial pressure index and changes in limb volume following balloon angioplasty for leg ischaemia.

OBJECTIVES: To investigate the association between changes in the ankle-brachial pressure index (ABPI) and simultaneous changes in calf volume following percutaneous transluminal angioplasty (PTA) for chronic leg ischaemia. MATERIALS: A total of 37 consecutive patients undergoing PTA for chronic leg ischaemia. METHODS: Bilateral calf volume, as calculated from girth measurements, and ABPI were determined before PTA, and repeated 24 h and 1 week following the procedure. Changes in the calf volume of the treated leg, both absolute and relative to changes of the non-treated leg, were then related to simultaneous changes in ABPI. RESULTS: Twenty-four hours following PTA, the calf volumes of both legs were decreased, although the ratio of the treated: untreated leg had increased by 2.4% (CI + 1.1-3.7, p < 0.01). After 1 week there was no difference in calf volume. These patterns were observed both in the 21 patients who had ABPI improvement of 0.15 or more 1 week following PTA, and in the 16 whose ABPI was unchanged. In the former group ABPI improved by a further 0.13 between 24 h and 1 week following PTA (p < 0.05), but there was no relationship between this delayed ABPI increase and simultaneous changes in calf volume. CONCLUSIONS: We did not detect any significant calf swelling following PTA. Furthermore, changes in ABPI were not related to changes in calf volume.

Angioplasty, Balloon↗

PubMed1997

The nature and importance of changes in toe-brachial pressure indices following percutaneous transluminal angioplasty for leg ischaemia.

OBJECTIVES: To document changes in toe-brachial pressure indices (TBPI) during the 6 months following percutaneous transluminal angioplasty (PTA) and relate these changes to restenosis. Furthermore, to ascertain the effect of administering a vasodilator, glyceryl trinitrate (GTN), immediately following PTA. DESIGN: Eighty-three technically successful PTA procedures were studied. Fifty-six were for intermittent claudication, 14 for ischaemic rest pain, and 13 for non-healing ulcers. Immediately following balloon dilatation an intra-arterial bolus of either 150 micrograms GTN, with or without a 10 mg GTN patch for 24 h, or a saline placebo was administered. TBPI were measured before and for 6 h after PTA and then at 24 h, 1 week, 1 month and 6 months. At this time, patency at the PTA site was determined by arteriography. RESULTS: There was continuing TBPI improvement over 1 month in patients given saline following PTA. In patients given GTN, peak TBPI was achieved by 1 week, and corresponded with the TBPI observed immediately following GTN administration. Restenosis occurred in 27 (33%) patients, and was significantly more frequent following the procedures for rest pain or ulceration, or where a TBPI increase of more than 0.15 by 1 week was observed. CONCLUSIONS: Haemodynamic changes following PTA continue for at least 1 month, can be modified by GTN administration, and are predictive of subsequent restenosis. Measuring the TBPI increase during the first week following PTA underestimates total improvement, and may give false reassurance with respect to recurrent disease.

Aged↗

PubMed1997

Pathophysiology of venous leg ulceration--an update.

The microcirculatory component of the pathophysiology of venous ulceration is now attracting considerable research interests, but is still far from fully elucidated. Currently, the central role is filled by the inappropriately activated white cell and its interaction with the endothelium. Interstitial oedema, pericapillary fibrin cuff and capillary microthromboses could all fit in with this hypothesis. However, there are other demonstrated changes, for instance in lymphatic drainage, intrinsic fibrinolysis and hemorheological changes which also need to be taken into account. The interaction between the microcirculatory changes is an obvious target for the systemic pharmacotherapy of venous ulceration.

Endothelium, Vascular↗

PubMed1996

Prostanoid drug therapy for peripheral arterial occlusive disease--the European experience.

The most serious threat to a claudicant is not the possible future need for a major amputation, but rather that the medium-term mortality is two to three times that of the general age-matched population. In patients with more severe disease in the legs, approximately 45% will have had a major amputation or be dead within a year of developing rest pain, ulcers or gangrene. These are the challenges for pharmacotherapy in peripheral arterial occlusive disease. In the short and medium term, pharmacotherapy can only have a significant effect by modifying the microcirculatory response to the low perfusion pressure caused by the arterial disease. The microcirculatory changes in the leg in severe leg ischaemia are ill understood, but theoretically a number of pharmacological effects could be beneficial. In practice, the only type of drugs widely tested clinically in severe leg ischaemia are prostacyclin and its analogues. In the last 12 years the results of properly controlled randomized trials involving patients with chronic limb ischaemia have been carried out in approximately 2000 patients in Europe. The largest number were entered into trials using the prostacyclin analogue iloprost. Some of these trials have shown a significant benefit compared to placebo in terms of major amputation or death during the 6 months following a 2-4 week course of intravenous iloprost. The possible future indications for this type of therapy, as well as the use for prostaglandins in claudicants, is discussed.

Arterial Occlusive Diseases↗

PubMed1996

Influence of blood cells and blood flow on venous endothelium.

The principal emphasis in the past has been on the physical characteristics of the vein wall and to some extent the flow characteristics of the blood it contains. The interaction between the blood cells and the venous endothelium has been largely neglected until recently. This brief review summarises the secretion by the endothelium of such important substances as fibrinolytic agents, antiplatelet agents and venodilators. Many of these secretory activities are modulated by the wall shear stress which in turn is related to the rheological properties of the blood. The rheological properties of bulk venous blood have been shown to be significantly abnormal in patients with venous hypertension. Such haemodynamic and haemorheological alterations also play an important role in the interaction between the formed elements of blood and the vessel wall. Most recently this has assumed the importance in relation to the margination and adhesion of white cells to the endothelium and the subsequent activation of the white cells. Interaction between the circulatory blood and the venous endothelium probably plays an important role in the pathophysiology of both simple varicose veins and the more serious complications of venous disease such as thrombosis.

Cell Adhesion↗

PubMed1995

[Epidemiology and natural history of arterial diseases of the lower limbs].

Symptomatic arterial disease in the legs is common and asymptomatic disease is even more common. However the majority of these patients do not develop disabling intermittent claudication and the local disease tends to run a benign course, particularly in women, with less than 10% to 15% ever requiring active intervention. With current therapy the incidence of major amputation is only 1% to 3%. By contrast however the very few patients who develop critical leg ischaemia have a prognosis as serious of that as an incurable malignant cancer. Only little over half of these patients will be alive without a major amputation a year after developing critical leg ischaemia. Perhaps the most important results of epidemiological studies in patients with arterial disease in the legs is that both symptomatic and asymptomatic disease increases mortality by a factor of 2 to 3 compared to subjects without significant arterial disease in the legs. One obvious implication of this is the need to redirect attention to the secondary prevention of cardiovascular morbidity or mortality in these patients even though their symptoms may be confined to the leg.

Amputation, Surgical↗

PubMed1995

Clinical outcome and restenosis following percutaneous transluminal angioplasty for ischaemic rest pain or ulceration.

The role of percutaneous transluminal angioplasty in the management of severe leg ischaemia is controversial. To investigate further the efficacy of angioplasty and the clinical consequences of restenosis, a randomly selected cohort of 29 patients with ischaemic rest pain or ulceration was studied for 6 months after a technically successful balloon angioplasty. All patients had digital subtraction arteriography at the end of follow-up. Seven of 15 patients undergoing the procedure for rest pain had sustained relief from the initial dilatation. Partial or complete healing was noted in all 14 patients with ulceration and was maintained at 6 months in 11 despite significant (greater than 30 per cent) restenosis at the angioplasty site in eight. There were no complications or clinical deterioration associated with the procedure. Angioplasty is an effective method for treating the severely ischaemic leg, especially when used to achieve ulcer healing; restenosis is often clinically unimportant.

Aged↗

PubMed1995

Two cases of colo-ovarian cyst fistula.

Fistula between the large bowel and an ovarian cyst is a recognised but rare pathological entity. We present two cases of colo-ovarian cyst fistula, the first occurring as a result of diverticular disease of the sigmoid colon and the second complicating a cystadenocarcinoma of the ovary. The aetiology of colo-ovarian cyst fistula is reviewed and the differential diagnosis is discussed.

Aged↗

PubMed1995

Pharmacologic treatment of venous leg ulcers.

In terms of prevalence, total cost and morbidity, venous leg ulcers are probably by far the most important type of ulcerations in the leg. The macrocirculatory defect leading to a raised ambulatory venous pressure is now accepted as a common initial pathologic pathway. Most current treatment modalities, such as surgery or external compression, are designed to control the macrovascular defect. However, it is the microcirculatory consequences of the venous hypertension that give rise to the trophic skin changes and ultimately to ulceration. At this microcirculatory level, pharmacotherapy may be a useful adjunct in the treatment of venous leg ulcers. The microcirculatory pathophysiologic changes include decreased fibrinolytic activity, elevated plasma fibrinogen, microcirculatory thrombi, and inappropriate activation of the white blood cells. The oxidative burst from the activated white cells probably plays a key role by releasing locally leukocyte-derived free radicals, proteolytic enzymes, cytokines, platelet-activating factor, and a number of other noxious mediators. An important additional component in recalcitrant venous ulcers is co-existing arterial disease, which is probably present in 15-20% of cases. Decreased arterial perfusion pressure will further aggravate the ischemic changes caused by the venous hypertension. Pentoxifylline downregulates leukocyte activation, reduces leukocyte adhesion, and also has fibrinolytic effects. A number of clinical studies have therefore been carried out to examine the clinical efficacy of pentoxifylline in treatment of venous leg ulcers. Probably the largest published placebo-controlled, double-blind randomized study was reported in 1990. In this study, 80 patients received either pentoxifylline 400 mg three times a day orally or matching placebo for 6 months or until their reference ulcer healed if this occurred sooner. Complete healing of the reference ulcer occurred in 23 of the 38 patients treated with pentoxifylline compared to 12 of the 42 patients treated with placebo. The odds ratio in favor of pentoxifylline was 1.81 (95 confidence intervals 1.20-2.71).

Cardiovascular Agents↗

PubMed1995

Microcirculation in venous disorders: the role of the white blood cells.

The haemodynamic hallmark of chronic venous disease in the legs is raised ambulatory venous pressure. This is probably the principal cause of both the symptoms of long-standing varicose veins and the trophic changes round the ankle characteristics of chronic venous insufficiency, presumably by an effect on the microcirculation. The microcirculatory consequences of raised venous pressure include morphological changes, as well as functional abnormalities ranging from haemorheological changes, increased capillary permeability and abnormalities of fibrinogen metabolism to trapping of white blood cells in the dependent legs. This last is now known to be accompanied by sequestration of platelets, which is irreversible. It is postulated that leucocyte activation releases cytokines, leucocyte-derived oxygen free radicals, proteolytic enzymes and platelet activating factor. It has been shown that external compression not only relieves stasis but also decreases white cell trapping. A strategy for management of the complications of venous disease should therefore be aimed at treatment of both the macrocirculatory haemodynamic defect and the microcirculatory abnormalities. The latter is an ideal target for systemic pharmacotherapy.

Humans↗

PubMed1994

Reliability of ankle:brachial pressure index measurement by junior doctors.

Ankle:brachial pressure index (ABPI) measurements are often performed by junior medical staff with little experience of the technique. The accuracy of such measurements is unknown. Two newly qualified doctors with no training in the use of Doppler ultrasonographic flowmeters performed ABPI measurement in 38 limbs (experiment 1). Two other newly qualified doctors then underwent a formal training session before, as well as continuous instruction during, ABPI measurements in 23 limbs (experiment 2). The doctors' measurements were compared with those obtained by experienced vascular technicians. The mean difference in ABPI measurement between the doctors and technicians in experiment 1 was greater than that in experiment 2 at both the dorsalis pedis (P < 0.05) and posterior tibial arteries. Nearly 30 per cent of the doctors' ABPI measurements in experiment 1 differed from those of the technicians by more than 0.15, in comparison with only 15 per cent of the measurements performed in experiment 2. Junior doctors should undergo formal training before performing ABPI measurements.

Aged↗

PubMed1994

Hypercoagulable states in patients with leg ischaemia.

Hypercoagulable states are found in up to 10 per cent of patients with a history of unexplained venous thrombosis. To investigate the prevalence in arterial thrombosis, thrombophilia screening was performed on 124 patients who had previously undergone lower-limb revascularization, 45 claudicants and 27 controls. Of the patients who had undergone revascularization 40 per cent had a hypercoagulation abnormality (low levels of protein C, protein S and antithrombin III or presence of the lupus anticoagulant) in comparison with 27 per cent of claudicants and 11 per cent of controls (P < 0.01). Furthermore, patients who had suffered reocclusion after revascularization were significantly more likely to have a hypercoagulation abnormality than those who had not (P < 0.05), even if the occlusion had occurred more than 6 months previously. Lupus anticoagulant was the abnormality most frequently detected and, like low protein C levels, was found only in patients with peripheral vascular disease. It appears that hypercoagulable states are common in patients with arterial disease and may predispose to failure of revascularization.

Aged↗

PubMed1994

A meta-analysis of randomized placebo control trials in Fontaine stages III and IV peripheral occlusive arterial disease.

In patients with Fontaine Stage III and IV POAD unsuitable for arterial reconstruction, Iloprost, a prostacyclin analogue, has been shown in six RCTs to have a significant (p < 0.05) beneficial effect with regards to the probability of being alive with both legs at six months follow-up. Iloprost has significant (p < 0.05) beneficial effects over placebo on ulcer healing and pain relief, but these were relatively soft endpoints to study when side effects may have unblinded many observers and patients. Further studies are indicated to investigate the possible benefit of repeated courses of treatment with Iloprost in patients with non-reconstructable Fontaine Stage III and IV POAD as well as studies looking at patients who may be suitable only for relatively high risk reconstructions. Meta-analysis of all other RCTs of pharmacotherapeutic agents in patients with Fontaine Stage III and IV POAD showed no significant benefit over placebo for any of the endpoints reported.

Alprostadil↗