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Biomedical subjects

A Halliday

Publications and source records attributed to A Halliday.

At least 19 recordsLinked to original sources
PubMed2006

The prevalence of thrombophilia in patients with symptomatic peripheral vascular disease.

BACKGROUND: The aim of this prospective study was to establish the prevalence of thrombophilia and hyperhomocysteinaemia using a comprehensive screen in patients with peripheral vascular disease. METHODS: A total of 150 patients with peripheral vascular disease (with an ankle brachial pressure index of less than 0.8) underwent thrombophilia screening (protein C and protein S, antithrombin, lupus anticoagulant, activated protein C resistance and factor V Leiden and prothrombin mutations). Fasting homocysteine assays were also performed. RESULTS: A thrombophilia defect was found in 41 patients (27.3 per cent). The commonest was protein S deficiency, found in 17 patients (11.3 per cent). Others included factor V Leiden mutation, found in 10 (6.7 per cent) and protein C deficiency, found in six (4.0 per cent). Lupus anticoagulant and prothrombin mutation were both found in six (4.0 per cent). One patient had an antithrombin deficiency. Only the presence of critical ischaemia was associated with a positive thrombophilia screen on single variable analysis (P = 0.03). Hyperhomocysteinaemia was present in over a third of the study group (37.3 per cent): 45 defined as moderate and 11 as intermediate. CONCLUSION: A quarter of patients with peripheral vascular disease had evidence of thrombophilia, and a third had hyperhomocysteinaemia.

Aged↗
PubMed2005

An immunogenic cathepsin F secreted by the parasitic stages of Teladorsagia circumcincta.

Teladorsagia circumcincta is a common, pathogenic abomasal nematode of sheep. In order to improve disease control in parasite isolates resistant to several anthelmintics, alternative methods must be sought. Sheep develop acquired immunity to T. circumcincta so vaccination is a valid option for control. For this reason, we are investigating parasite excretory/secretory products for molecules, which have potential to invoke protective immunity against T. circumcincta. Here, we describe experiments in which we identified a novel, immunogenic cathepsin F secreted by L4 T. circumcincta. This protease, initially identified by mass spectrometry analysis, is the most abundant molecule in excretory/secretory products released in vitro by T. circumcincta harvested at 5, 6 or 9 days p.i. and is a target of specific, local IgA responses in sheep which are immune to challenge infection. The full-length cDNA encoding this secreted protease was isolated. Sequence and phylogenetic analyses indicated that the protease (designated T. circumcincta cathepsin F-1, Tci-CF-1) belongs to the cathepsin F class and exhibits greatest identity (>60%) to expressed sequence tags present in the Ostertagia ostertagi and Haemonchus contortus expressed sequence tag databases. Tci-CF-1 also displays high identity to hypothetical proteins identified in the genomes of Caenorhabditis elegans and Caenorhabditis briggsae, both proteins having been described as cathepsin F enzymes. Specific inhibitor binding assay of larval excretory/secretory products confirmed the classification of this excretory/secretory component as a cathepsin F. Reverse transcription-PCR studies indicated that Tci-cf-1 is developmentally regulated and is particular to the host parasitic stages of T. circumcincta. The abundance, immunogenicity and temporal expression pattern of Tci-CF-1 make this a potential vaccine candidate for teladorsagiosis.

Amino Acid Sequence↗
PubMed2004

Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.

BACKGROUND: Among patients with substantial carotid artery narrowing but no recent neurological symptom (stroke or transient ischaemia), the balance of surgical risks and long-term benefits from carotid endarterectomy (CEA) was unclear. METHODS: During 1993-2003, 3120 asymptomatic patients with substantial carotid narrowing were randomised equally between immediate CEA (half got CEA by 1 month, 88% by 1 year) and indefinite deferral of any CEA (only 4% per year got CEA) and were followed for up to 5 years (mean 3.4 years). Kaplan-Meier analyses of 5-year risks are by allocated treatment. FINDINGS: The risk of stroke or death within 30 days of CEA was 3.1% (95% CI 2.3-4.1). Comparing all patients allocated immediate CEA versus all allocated deferral, but excluding such perioperative events, the 5-year stroke risks were 3.8% versus 11% (gain 7.2% [95% CI 5.0-9.4], p<0.0001). This gain chiefly involved carotid territory ischaemic strokes (2.7% vs 9.5%; gain 6.8% [4.8-8.8], p<0.0001), of which half were disabling or fatal (1.6% vs 5.3%; gain 3.7% [2.1-5.2], p<0.0001), as were half the perioperative strokes. Combining the perioperative events and the non-perioperative strokes, net 5-year risks were 6.4% versus 11.8% for all strokes (net gain 5.4% [3.0-7.8], p<0.0001), 3.5% versus 6.1% for fatal or disabling strokes (net gain 2.5% [0.8-4.3], p=0.004), and 2.1% versus 4.2% just for fatal strokes (net gain 2.1% [0.6-3.6], p=0.006). Subgroup-specific analyses found no significant heterogeneity in the perioperative hazards or (apart from the importance of cholesterol) in the long-term postoperative benefits. These benefits were separately significant for males and females; for those with about 70%, 80%, and 90% carotid artery narrowing on ultrasound; and for those younger than 65 and 65-74 years of age (though not for older patients, half of whom die within 5 years from unrelated causes). Full compliance with allocation to immediate CEA or deferral would, in expectation, have produced slightly bigger differences in the numbers operated on, and hence in the net 5-year benefits. The 10-year benefits are not yet known. INTERPRETATION: In asymptomatic patients younger than 75 years of age with carotid diameter reduction about 70% or more on ultrasound (many of whom were on aspirin, antihypertensive, and, in recent years, statin therapy), immediate CEA halved the net 5-year stroke risk from about 12% to about 6% (including the 3% perioperative hazard). Half this 5-year benefit involved disabling or fatal strokes. But, outside trials, inappropriate selection of patients or poor surgery could obviate such benefits.

Aged↗
PubMed2004

Prevalence and risk of thrombophilia defects in vascular patients.

This paper reviews the available data on the prevalence of thrombophilia defects in patients with peripheral vascular disease (PVD) and attempts to delineate the risk of failure of vascular intervention in these patients. The prevalence of thrombophilia in stable claudicants is 25% and increases to 40% in those requiring revascularisation, compared to only 11% in the control group. The overall prevalence of thrombophilia defects in patients with premature atherosclerosis appears to be between 15 and 30%. The prevalence in the typical cohort of patients with PVD appears to be similar. All these studies have recruited patients with symptoms significant enough to warrant intervention. The overall prevalence of thrombophilia calculated from these trials, therefore, may not be truly indicative of the general vascular population who may not even present primary or secondary healthcare. The risk of thrombotic occlusion following arterial revascularisation in patients with an identified thrombophilia defect appears to be almost three times that of patients with no evidence of a thrombophilia defect. The best management of these patients has not been determined and needs to be evaluated by prospective randomized trials.

Adult↗
PubMed2001

Simultaneous ultratrace determination of Zr and Nb in chromium matrixes with ICP-dynamic reaction cell MS.

A dynamic reaction cell (DRC) has been used to minimize the formation of metal-argide ions in inductively coupled plasma mass spectrometry and applied to the determination of Zr and Nb in Cr-rich samples. The formation of ArCr+ species from the plasma gas and the sample matrix was reduced by ion molecule reactions inside a DRC of the ICPMS used. Hydrogen was used as reaction gas, and the efficiency in the reduction of ArCr+ was similar to that of other plasma-based polyatomic ions as reported in an earlier study. The formation of CrOx+ ions is enhanced when the DRC is operated in pressurized mode. Adjustment of the transmission properties of the band-pass quadrupole to reject precursor ions can be achieved without dramatic decrease of sensitivity but with a significant improvement in the signal/background ratio. Measurements in solutions containing concentrations of up to 2 g/L Cr showed that the determination of Nb and Zr is possible in the nanogram per liter range in such a matrix. The limits of detection for Nb and Zr in pure Cr metal have been estimated at 2 ng/g for Nb and 5 ng/g for Zr. Analysis of basaltic reference samples resulted in very good agreement with previously published data.

Journal Article↗
PubMed2001

Thromboelastography: a reliable test?

The thromboelastograph (TEG), a measure of global haemostasis, is routinely used during cardiac and hepatic surgery to optimize blood product selection and usage. It has recently been suggested that it may also be a useful tool to screen patients with hypercoagulable states. Limited published data on performance characteristics has led to speculation regarding its consistency and, therefore, validity of the results. This study was designed to assess the effect of stability of blood samples prior to testing, repeated sampling, intra- and inter-assay variability using the native, celite, tissue factor (TF) and Reopro-modified TEG. Analysis of native and celite samples after storage over 90 min showed a period of instability up to 30 min. Thereafter, all parameters between 30 and 90 min were stable [P = not significant (NS)]. When the same sample was repeatedly assayed, both native and celite TEG parameters showed a significant change towards hypercoagulability (P < 0.01), whereas the TF and Reopro-modified TEG showed no change. Intra- and inter-assay variability on samples tested after 30 min showed excellent reproducibility for all parameters (P = NS). The data suggest that the TEG is a useful tool in haemostasis but requires a formal standard operating procedure to be adopted that takes into account the initial period of sample instability.

Blood Specimen Collection↗
PubMed2000

Carotid endarterectomy: indications for symptomatic and asymptomatic stenosis.

There have been several clinical trials pertaining to carotid endarterectomy in the last two decades. These studies have provided long-awaited information regarding the risks and benefits of surgery for carotid stenosis. This paper outlines the key results for patients with symptomatic and asymptomatic stenosis. A scheme for the identification of patients likely to benefit from surgery, and persistent areas of controversy and uncertainty, are reviewed.

Carotid Stenosis↗
PubMed1999

Vascular surgical society of great britain and ireland: carotid angiography is used more selectively in the asymptomatic carotid surgery trial

BACKGROUND: The ongoing Asymptomatic Carotid Surgery Trial (ACST) has randomized more than 1900 patients to determine whether carotid endarterectomy prolongs stroke-free survival compared with best medical treatment alone. Previously the Asymptomatic Carotid Atherosclerosis Study demonstrated that preoperative angiography caused stroke or death in 1 per cent of patients, and many centres have now reduced or abandoned this practice. This study determined the changing practice of carotid angiography in the ACST. METHODS: Collaborating surgeons completed questionnaires annually on their use and method of angiography. Information on patients in the ACST who had angiography at randomization was also obtained. RESULTS: In 1993, 77 per cent of responding collaborators always performed preoperative angiography and 23 per cent used angiography selectively. This trend has reversed: by 1997, 26 per cent always used preoperative angiography, 70 per cent of respondents used preoperative angiography selectively and 4 per cent had abandoned angiography (P < 0.001, chi2 for trend). Information on carotid angiography at randomization has to date been obtained on 1141 patients in the ACST. Some 44 per cent (497 of 1141) had carotid angiography at randomization. Surgical patients had angiography more commonly than those in the medical group (49 versus 42 per cent; P < 0.03, chi2 test). Changes in carotid angiography were analysed by year of randomization. In 1993, 61 per cent of patients randomized had carotid angiography compared with 42 per cent in 1996 and 1997 (P < 0.001, chi2 for trend). The use of carotid angiography was not related to degree of stenosis estimated by Doppler ultrasonography. CONCLUSION: In the ongoing ACST, there is increasingly selective use of carotid angiography. Less than half the patients in this study had carotid angiography and the use of angiography is now decreasing. This has important implications for validation of carotid duplex in this trial and in future studies.

Journal Article↗
PubMed1998

Are we detecting and operating on high risk patients in the asymptomatic carotid surgery trial? The Asymptomatic Carotid Surgery Trial Collaborators.

OBJECTIVE: This study aims to determine whether asymptomatic carotid surgery trial (ACST) centres have entered and can identify high risk patients using duplex. DESIGN: Retrospective study. MATERIALS AND METHODS: Eighty-six vascular laboratories collaborating in ACST were studied, Equipment, operator experience, methodology and interpretation criteria were assessed. The ACST randomisation data were examined to determine whether patients believed to be at higher risk of stroke because of tight stenosis, contralateral occlusion or echolucent plaque were randomised. RESULTS: Laboratories (92%) had colour duplex and 62% of all operators had > 3 years experience in carotid evaluation. The Doppler angle used to obtain peak velocity was 30-60 degrees in 65%, 60 degrees in 28% and 60-80 degrees in 6% of laboratories. Sixty-two per cent reported diameter reduction, 27% area reduction, and 11% used both methods. One-third of 1657 randomised patients were reported to have ipsilateral echolucent plaque. Median ipsilateral stenosis was 80%, 8% had contralateral occlusion and 8.5% had bilateral > 80% stenosis. CONCLUSIONS: Centres in ACST use experienced operators, high quality equipment and conscientious data recording. Variations in methods of determining carotid stenosis exist, but can be smoothed by simple data collection. Patients at higher perceived risk of stroke are being entered and with continued recruitment it should be possible to determine whether surgery improves disabling stroke-free survival.

Angiography↗
PubMed1998

Carotid duplex ultrasonography: importance of standardisation. Asymptomatic Carotid Surgery Trial Collaborators and Vascular Laboratories.

BACKGROUND: Carotid duplex ultrasonography (CDUS) is an established non-invasive tool for assessing patients with suspected carotid bifurcation disease. Current trends show an increased dependence on CDUS in recommending patients for stroke prevention surgery. The aim of the study was to evaluate routine practice in vascular laboratories across 26 countries participating in The Asymptomatic Carotid Surgery Trial (ACST), and to determine the areas which are in need of future standardisation if CDUS is to be the primary tool in recommending patients for CEA. METHODS: Retrospective. Information was gathered from questionnaires, and 22 on-site visits of vascular laboratories between August 1996 to September 1997. SETTING: Clinical vascular laboratory practice. PARTICIPANTS: Eligible participants were vascular laboratories of ACST collaborators. MEASURES: Laboratories were compared in 7 categories: ultrasound equipment, operators, experience, protocols, stenosis evaluation, interpretation criteria, and reporting. RESULTS: Information on 117 respondents showed that (i) experience: at least one operator in each laboratory had more than 3 years experience; (ii) equipment: 88% (103/117) had colour duplex capability; (iii) operators: 54% of laboratories had exams performed by technologists, 33% vascular surgeons, 28% radiologists, and 35% other. The most significant findings were in (iv) stenosis evaluation: only 29% (33/117) were using a standardised Doppler angle (this single factor may greatly alter exam results); and (v) interpretation criteria; with >41 different criteria reported. These specific laboratory variations can affect those patients considered appropriate for CEA. CONCLUSIONS: This study highlights the most significant areas for future standardisation to be Doppler angle and interpretation criteria, if CDUS is to be a primary tool in recommending patients for CEA, when indicated by clinical trial results.

Carotid Stenosis↗
PubMed1998

The prevalence of cerebral infarcts in the Asymptomatic Carotid Surgery Trial (ACST) in relation to prior contralateral symptoms.

BACKGROUND: The ACST has randomised over 1670 patients to determine if carotid endarterectomy (CEA) prolongs stroke free survival versus best medical treatment alone. Some patients have had contralateral symptoms to the side under investigation, for which CEA may have been performed. This study aims to determine the prevalence of hemispheric cerebral infarcts in relation to prior contralateral symptoms. METHODS: Patients with preoperative CT or MR scans were divided into those with prior contralateral stroke, cortical TIA, amaurosis fugax or no symptoms. RESULTS: There were 1144 patients with preoperative CT and 170 patients with MR scans. Incidence of contralateral hemispheric CT and MR infarcts were 19% (222/1144) and 20% (34/170) respectively. Those with prior contralateral stroke (141) had the highest incidence of hemispheric CT infarcts (62%). Those with TIA (129) had a 30% incidence of CT infarct. Incidence of hemispheric CT infarcts were 17% with amaurosis fugax (46) and 10% with no prior symptoms (803). Mantel-Haenszel test for linear association was significant (p < 0.001) for increasing severity of symptoms. Considering MR scans, those with prior contralateral stroke (17) had the highest incidence of hemispheric MR infarcts (53%). Patients with TIA (23) or amaurosis fugax (6) had a 27% incidence of MR infarction. Those with no prior symptoms (121) had a 14% incidence of MR infarcts. Mantel-Haenszel test was significant (p < 0.001). CONCLUSIONS: In the ACST, currently asymptomatic patients have an incidence of contralateral hemispheric CT and MR infarcts proportional to the severity of prior contralateral symptoms.

Brain↗
PubMed1998

Prevalence of asymptomatic CT infarcts in the ongoing Asymptomatic Carotid Surgery Trial (ACST).

BACKGROUND: The ACST has randomised over 1670 patients to determine if carotid endarterectomy (CEA) prolongs stroke free survival when compared with best medical treatment alone. This study aims to assess the prevalence of asymptomatic cerebral infarcts in patients grouped by sex, age, mean blood pressure (MBP), total cholesterol, diabetes and coronary artery disease (CAD). METHODS: The type of study was retrospective. Patients with preoperative CT scans were included. In those with previous stroke, only the contralateral cerebral hemisphere was studied for presence of infarcts. One thousand one hundred and forty-two patients were studied. RESULTS: The proportion of patients with CT infarcts was 19% (211/1142). Men (155/777) had a higher incidence of CT infarction (20% vs 15%, p = 0.01). Mean age was 68 years and mean MBP was 107 mmHg. The incidence of CT infarcts was not associated with age or MBP. Diabetics or those with definite CAD had no difference in the incidence of cerebral infarction. Diabetics with definite CAD (51/796) had a greater incidence of CT infarcts (33% vs 21%, p = 0.03) compared with those without evidence of CAD and diabetes together (745/796). CONCLUSIONS: In ACST, CT infarcts are more prevalent in men compared to women, and in diabetics with CAD. There was no difference in the incidence of CT infarction by age, mean BP, or by the presence of diabetes or CAD alone.

Adult↗