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Biomedical subjects

E Macaulay

Publications and source records attributed to E Macaulay.

7 recordsLinked to original sources
PubMed2006

Surgical revascularisation in patients with severe limb ischaemia induces a pro-thrombotic state.

Platelet and coagulation activation are implicated in the increased incidence of ischaemic events seen in patients with peripheral arterial disease. This study aimed to assess the effect of surgical revascularisation on platelet aggregation and coagulation in patients with severe limb ischaemia (SLI). Twenty-two patients had blood samples taken: prior to surgery, on reperfusion, 2, 24 and 48 h post-surgery. Platelet aggregation through COX-mediated and thrombin receptor activator peptide (TRAP)-stimulated GPIIb/IIIa pathways was measured by the Ultegra point of care system. Thrombin-antithrombin III Complex (TAT) and D-dimer were measured by ELISA. COX-mediated aggregation increased significantly at reperfusion and remained elevated at 24 h [median increase from baseline of 9% (range -16 to 33%) P = 0.011]. TRAP-stimulated aggregation increased significantly at reperfusion and remained elevated at 2 h post-surgery [median increase 18% (range -71 to 45%); P = 0.007]. TAT levels were significantly elevated from reperfusion and remained so at 48 h (P < 0.003), whereas D-dimer only increased at 24 h (P = 0.014). For the first time, we have demonstrated that in patients with SLI, platelet aggregation is increased following surgery and there is a mismatch in the balance between the coagulation and fibrinolytic pathways despite the use of aspirin and heparin. Thus in the early post-operative these patients exhibit a pro-thrombotic state.

Aged↗
PubMed2005

A preliminary study on the effects of exercising to maximum walking distance on platelet and endothelial function in patients with intermittent claudication.

BACKGROUND: Platelet and endothelial activation has been shown to be increased in patients with intermittent claudication (IC). Recent studies have suggested that exercise may induce further platelet activation. The aims of this study were to investigate the effect of exercising to maximum walking distance on platelet and endothelial function in patients with intermittent claudication who were receiving statin and aspirin therapy compared with age matched healthy controls. METHODS: Platelet aggregation through COX-mediated and thrombin receptor activator peptide (TRAP)-stimulated GPIIb/IIIa pathways was measured by the Ultegra point of care system in 20 patients with IC on aspirin and 20 healthy volunteers before, immediately and 1h after exercising to treadmill maximal walking distance (MWD). Soluble P-selectin, vWF and sICAM were measured using an enzyme linked immuno-sorbent assay technique. RESULTS: Baseline platelet aggregation was significantly reduced in patients with IC compared to volunteers (p<0.05). In patients, exercising to MWD significantly reduced platelet aggregation (COX, median -5% [range -24 to 13%]; p = 0.02; GPIIIa/IIb, median -13% [range -72 to 33%]; p = 0.02) immediately post-exercise which returned to baseline values at 1 h. There was no change in the healthy volunteers following the same median duration of exercise. Baseline sP-selectin levels were higher in the patients with IC compared to the healthy volunteers [Median values (interquartile range), 42.72 (33.28-54.24) versus 29.16 (24.40-34.10), p = 0.0003] but there were no differences in vWF levels. Both sP-selectin and vWF levels increased significantly in the control and patient group following exercise (p<0.005). sICAM were higher at baseline in the patients with IC but were unchanged following exercise [Median values (interquartile range),560.9 (405.5-739.4) versus 467.0 (325.7-643.4), p<0.05]. CONCLUSION: This study is the first to show that platelet aggregation is reduced immediately following treadmill exercise to maximum walking distance in patients with IC despite a rise in sP-selectin and vWF, suggesting endothelial activation. The inhibition of platelet aggregation after exercise in subjects on antiplatelet and statin therapy suggests that exercise is unlikely to exacerbate platelet thrombus formation in patients with IC.

Aged↗
PubMed2003

Management of secondary risk factors in patients with intermittent claudication.

OBJECTIVES: The first line management of patients with intermittent claudication is "best medical therapy" i.e., smoking cessation, exercise, antiplatelet therapy and risk factors modification. The aim of this study was to assess the current management of risk factors in primary care and to compare General Practitioner (GP) attitudes and actual management. DESIGN AND METHODS: Postal questionnaire of all 336 GPs in the referral area (Grampian, Scotland). Questionnaire and measurement of serum cholesterol, blood glucose and HbA1c of new clinic patients (n = 104) with claudication referred by general practitioners. RESULTS: A 73% GP response rate was obtained. Ninety-five percent of GPs would treat risk factors. The vast majority would prescribe aspirin, yet 28% of patients were on no anti-platelet therapy. Eighty-nine percent of GPs would advise an increase in exercise but only 14% of patients recalled being told to do so. One in seven of the GPs would not check serum cholesterol, 18% considered cholesterol lowering therapy to be primary prevention and 41% would only treat levels above 5.5 mmol/l. Eighty-five percent of patients were on a statin or had a cholesterol above 5 mmol/L. Seventy-seven percent of GPs would check glucose levels, and 14% of patients were found to be previously undiagnosed diabetics. CONCLUSIONS: Risk factors in claudicants are suboptimally managed. Urgent guidelines for the specific management of claudicants by general practitioners, as well as strategies to ensure their implementation, are required.

Adult↗
PubMed1999

Stereotactically delivered cranial radiation therapy: a ten-year experience of linac-based radiosurgery in the UK.

In 1989, linear accelerator (linac)-based cranial stereotactic radiation therapy ('radiosurgery') was introduced in the UK at St Bartholomew's Hospital; a new, relocatable stereotactic frame was first used at the same time, allowing fractionated stereotactic radiotherapy. In the first decade of clinical practice using this technology, some 200 patients with blood vessel tumours/malformations have been treated, together with another 200 suffering from other conditions. The usefulness of this technique for cerebral arteriovenous malformations (AVM) has been demonstrated, and also a significant cure rate for AVM of >3 cm diameter (which is larger than for those previously reported after treatment on the gamma unit), albeit attended by a higher complication rate. The epilepsy associated with AVM is much improved by successful radiotherapy. The usefulness of radiosurgery for glomus tumours has been confirmed and new data published on the efficacy of the technique for haemangioblastoma, with new radiation therapy strategies designed for patients with von Hippel-Lindau disease. The acoustic neuroma treatment results have included improvements in hearing (a result not reported in the gamma unit literature), which are ascribed to the lower internal dose gradient within the target volume. Fractionation will, it is argued, also lead to sparing of the special sensory cochlear nerve. The risks of radiosurgery to the brainstem for chordoma of the mid-clivus are reduced by using a 'spacer' technique for the prepontine space. For meningiomas involving the cavernous sinus, conventionally fractionated radiotherapy is recommended when the meningeal base diameter exceeds 3.0 cm and radiosurgery (utilizing fractionation where appropriate) is advised for smaller lesions. Thus far, radiosurgery indications for pituitary adenomas have been restricted to recurrences after conventional radiotherapy, usually those in the cavernous sinus. In therapy for recurrent craniopharyngioma, it is argued that fractionation delivered via the relocatable frame will be important, particularly when the disease envelops the optic chiasma. For semicystic/semisolid craniopharyngiomas, the stereotactic delivery of colloidal yttrium-90 into a cystic element is useful, while stereotactic radiosurgery is delivered to the solid component. Staff at this centre consider that radiosurgery for low-grade gliomas, perhaps as boost therapy after conventional fractionation, is worthy of more research. We have been extremely selective in the use of radiosurgery for brain metastases (2% of patients, compared with about 30% in some Gamma Knife units), but future indications may become broader, probably using it as a booster technique after whole-brain conventionally-fractionated radiotherapy. Positron emission tomography scanning, co-registered with magnetic resonance imaging, allows the 'boost' concept in radiosurgery to become a sophisticated and accurate reality. Post-radiosurgical sequelae have been placed within a standard framework classification. New observations are being made with regard to subacute reactions: late-responding intrinsic and extra-axial tumours may swell in the subacute period, prior to shrinkage, and be attended by symptomatic surrounding brain oedema.

Adenoma↗
PubMed1999

Stereotactic radiosurgery. VI. Posterior displacement of the brainstem facilitates safer high dose radiosurgery for clival chordoma.

The current 'best treatment method' for clival chordoma is regarded as radical surgical resection followed by radiation therapy; radiosurgery usually plays a major part in the radiation therapy programme. From primate radiation biology studies and from clinical observations, the brainstem is known to be the most radiosensitive part of the central nervous system. The tolerance of the brainstem to high single radiosurgical doses of radiation is limited (all the more so in programmes such as our own where conventionally fractionated radiotherapy precedes radiosurgery or the patient has relapsed after conventional radiotherapy--as in the patient reported here). In this report we describe the operative displacement of the brainstem posteriorly at time of resection such that the proportion of the prescribed postoperative radiosurgical dose received by the brainstem is greatly reduced (by the order of 50%). The gains perceived to accrue from this technique are quantified from isodosimetric considerations not only in dose sparing to the brainstem, but importantly in that the dose to the clival chordoma may be highly significantly increased without exceeding current accepted tolerance brainstem dose limits. Two patients have received this joint surgical/radiosurgical approach to date; the second case is presented here in detail.

Brain Stem↗