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Biomedical subjects

J A Dormandy

Publications and source records attributed to J A Dormandy.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

Infrapopliteal angioplasty for limb salvage.

Fourteen infrapopliteal angioplasties were performed in 13 patients with critical limb ischaemia. Clinical indications were rest pain, ulceration, gangrene or a critically ischaemic limb from a graft occlusion secondary to an infrapopliteal lesion. The average ankle-brachial ratio was 0.22 in non-diabetics. Technical success was achieved in all lesions with an average increase of Doppler ratios of 0.5. Of the 13 patients, 11 (85%) showed early clinical improvement (with average length of follow-up of 8 months, range 1-18 months). With the introduction of smaller lower profile catheters, hydrophilic and steerable wires and the advent of digital subtraction angiography, infrapopliteal angioplasty can now be performed successfully and with few complications. The presence of spasm should be aggressively treated with intra-arterial nitroglycerin or verapamil.

Aged↗
PubMed1993

The differences in early haemodynamic response between surgery and angioplasty after successful re-opening of the superficial femoral artery.

In 40 patients with superficial femoral artery disease we prospectively evaluated the effect of angioplasty (n = 20) or femoropopliteal bypass (n = 20) on the ankle-brachial pressure index (ABI) using the Doppler ultrasound probe. The ABI was measured as a baseline 1 day before the procedure, 1 day after the procedure and 30 days later. In the angioplasty group the baseline ABI was 0.57 (0.11), increasing to 0.74 (0.26) 1 day postangioplasty and increasing further to 0.88 (0.26) after 30 days. The increase in ABI over 30 days was significantly greater than the increase over 1 day. In the femoropopliteal bypass group the baseline ABI was lower at 0.46 (0.17). However 1 day postoperatively it had increased to 0.92 (0.2) with almost no further increase at 30 days [0.95 (0.17)]. We concluded that by contrast to a surgical bypass where there was a large improvement in the ABI over the first day, the ABI following angioplasty continued to improve significantly beyond the first day.

Aged↗
PubMed1993

Leucocyte count: a predictor of early femoropopliteal graft failure.

The patency of 90 elective femoropopliteal reconstructions was assessed 6 months after surgery. The preoperative white cell count was found to be a highly significant predictor of early graft failure (P < 0.0001) independent of other previously recognized predictors of occlusion such as smoking and run-off.

Aged↗