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Biomedical subjects

A J Fox

Publications and source records attributed to A J Fox.

At least 73 records · Page 4Linked to original sources

The immediate impact of opening an adult high dependency unit on intensive care unit occupancy.

We assessed the hourly occupancy of our intensive care and high dependency units over an 8-week period commencing on the day our high dependency unit opened. Using criteria established by the working group on 'Guidelines on Admission to and Discharge from Intensive Care and High Dependency Units' published by the National Health Service Executive, we defined each patient daily as intensive care or high dependency status. Compared with hourly occupancy figures obtained before the high dependency unit opened, occupancy of the intensive care unit by high dependency patients has been shown to decrease significantly from 21.6% to 11.2%. Use of intensive care beds became more appropriate, their occupancy increasing significantly from 63.7% to 73.4%. A significant decrease in readmissions occurred, supporting the hypothesis that having high dependency beds reduces the number of patients discharged prematurely to the wards.

APACHE↗

Cerebral perfusion monitored using transcranial Doppler during acute anaphylaxis.

We present a case of severe acute anaphylaxis that occurred during preparation of a patient for carotid endarterectomy. Intra-arterial blood pressure and transcranial Doppler monitoring had been established before the anaphylactic reaction began and therefore the changes in arterial blood pressure and middle cerebral artery blood-flow velocity could be observed as they happened. This made it possible to assess directly the effectiveness of our management, which followed the resuscitation guidelines issued by the Association of Anaesthetists. In particular, this was a rare opportunity to confirm whether the recommended management is effective in restoring cerebral blood flow, and not just blood pressure, in a 'real life' situation, as most resuscitation information is based on laboratory-based animal studies. Evidence is presented which suggests that the administration of adrenaline in this setting is associated with increases in cerebral blood flow that are independent of arterial blood pressure.

Aged↗

Upper airway reactivity and upper respiratory tract infection: effect of nebulized lidocaine.

Patients presenting for elective anaesthesia and surgery may be suffering with, or recovering from, a recent upper respiratory tract infection. Airway reflexes are heightened and these individuals may be more likely to suffer airway complications on administration of general anaesthesia. We have examined the effect of nebulized lidocaine on upper airway reflexes in such subjects. Using dilute ammonia as a chemical stimulus to the upper airway, we measured upper airway reactivity in 15 volunteers (aged 22-43 yr) with symptoms of an upper respiratory tract infection for 4 days or less. The threshold concentration of ammonia producing a brief reduction in inspiratory flow was determined. Measurements were made before and after administration of a nebulized solution of 4% lidocaine 4 ml or saline. After a 2-h interval the procedure was repeated with the alternative solution. The order of administration was randomized. The observer was blind to the solution given. Ammonia threshold was found to increase in subjects after nebulized lidocaine, from a median value of 327 (range 76-878) ppm to 878 (251-1620) ppm (P = 0.0007, Wilcoxon); there was no significant change after nebulized saline. After a convalescence period of at least 4 weeks, with no return of symptoms in the preceding 2 weeks, ammonia threshold was reassessed. It was found to be increased in all 15 subjects. Comparison of the five different times of measurement showed a highly significant difference (P < 0.001, Friedman). Subsequent analysis showed significant differences (P < 0.05, Wilcoxon) between convalescent ammonia threshold and both baseline and post-saline nebulizer values. There was no significant difference between convalescent and post-lidocaine ammonia threshold. We conclude that in adult subjects, nebulized lidocaine attenuated the heightened airway reflex sensitivity associated with symptoms and signs of upper respiratory tract infection.

Adult↗

Effect of a remifentanil bolus dose on the cardiovascular response to emergence from anaesthesia and tracheal extubation.

We have examined the effect of remifentanil on the haemodynamic response to emergence from anaesthesia and tracheal extubation in 40 ASA I-II female patients undergoing diagnostic laparoscopy, in a randomized, double-blind study. All patients received a standard general anaesthetic comprising propofol, vecuronium and 1% isoflurane with 66% nitrous oxide in oxygen. At the end of surgery, a bolus dose of remifentanil 1 microgram kg-1 (n = 20) or saline placebo (n = 20) was given and tracheal extubation was performed when standard criteria were achieved. Arterial pressure and heart rate were recorded non-invasively at 1-min intervals from the end of surgery. Remifentanil attenuated the increase in both mean arterial pressure (P < 0.001) and heart rate (P < 0.05) at extubation. Mean time to extubation was 7.2 (SEM 0.6) min and 4.0 (0.5) min in the remifentanil and saline groups, respectively (P < 0.001). There was no difference in the incidence of coughing at extubation, time to recovery from anaesthesia or time to fitness for discharge from the recovery room.

Adolescent↗

Subtyping of methicillin-resistant Staphylococcus aureus isolates from the North-West of England: a comparison of standardised pulsed-field gel electrophoresis with bacteriophage typing including an inter-laboratory reproducibility study.

Bacteriophage typing is currently the recognised methodology for the typing of methicillin-resistant Staphylococcus aureus (MRSA) in the UK. Bacteriophage typing is less discriminatory and does not type all isolates compared with some molecular methods for typing MRSA. Chromosomal genotyping by pulsed-field gel electrophoresis (PFGE) is increasingly recognised as an improved method for typing MRSA, providing increased discrimination and typability. In this study the results of a comparison of bacteriophage typing and PFGE typing and subtyping are presented for a large collection of isolates from the North-West of England. Isolates belonging to the most frequently isolated epidemic methicillin-resistant Staphylococcus aureus (EMRSA) bacteriophage types 15 and 16 were typed by PFGE with further discrimination of common PFGE types possible into a number of subtypes. These results for a large collection of isolates demonstrate the improved typing of MRSA with PFGE. The widespread acceptance of PFGE for typing MRSA isolates has been hampered by the lack of standardised methodologies. Recently, a standardised PFGE strain typing system, known as the GenePath system has become available. The results of an inter-laboratory comparison of PFGE typing for a collection of isolates demonstrated good reproducibility with this system.

Bacterial Typing Techniques↗

Analysis of the human Ig isotype response to lactoferrin binding protein A from Neisseria meningitidis.

An effective vaccine for serogroup B meningococci has yet to be developed and attention has turned to subcapsular antigens of the meningococcus as possible vaccine candidates. Iron binding proteins are being studied, with most interest focused on the transferrin binding proteins (TbpA and TbpB) and the ferric binding protein (FbpA). This study describes the purification of lactoferrin binding protein A (LbpA) from two meningococcal strains and assesses the human isotype-specific serum antibody response to these proteins in patients with proven meningococcal disease due to a range of phenotypes. Overall, fewer than 50% of sera contained IgG that recognised LbpA isolated from either strain and this antibody response was not uniform between the two proteins. There was some evidence that the antibody response varied between meningococcal phenotypes. This study demonstrates that LbpA does not induce a highly cross-reactive antibody response, indicating that it is unlikely to be an effective vaccine antigen.

Antibodies, Bacterial↗

A three-dimensional cerebrovascular flow phantom.

We have constructed a life-sized fully three-dimensional (3D) rigid flow-through model of the cerebral vasculature. Average vessel diameters and lengths, taken from published values in the literature, were used to describe the geometry of our phantom; numerically controlled machining techniques were used to fabricate the model. Inflow to the phantom is provided through two internal carotid arteries and two vertebral arteries. Outflow is provided through the anterior cerebral arteries, the middle cerebral arteries, and the posterior cerebral arteries. The phantom includes the circle of Willis, and aneurysms of variable size may be attached at different locations. We have tested the model for geometric accuracy using high-resolution MR and CT imaging protocols, and have found that measured and prescribed diameters agree to within better than 4%. Flow dynamics, including waveform shape and flow division between branches, also mimic that seen in vivo, with flows within 16% (on average) of the prescribed values. We present 3D magnetic resonance angiography, digital subtraction angiography, and computed rotational angiography images of the phantom under conditions that mimic physiological situations.

Angiography, Digital Subtraction↗

Population genetic and evolutionary approaches to analysis of Neisseria meningitidis isolates belonging to the ET-5 complex.

Periodically, new disease-associated variants of the human pathogen Neisseria meningitidis arise. These meningococci diversify during spread, and related isolates recovered from different parts of the world have different genetic and antigenic characteristics. An example is the ET-5 complex, members of which were isolated globally from the mid-1970s onwards. Isolates from a hyperendemic outbreak of meningococcal disease in Worcester, England, during the late 1980s were characterized by multilocus sequence typing and sequence determination of antigen genes. These data established that the Worcester outbreak was caused by ET-5 complex meningococci which were not closely related to the ET-5 complex bacteria responsible for a hyperendemic outbreak in the nearby town of Stroud during the years preceding the Worcester outbreak. A comparison with other ET-5 complex meningococci established that there were at least three distinct globally distributed subpopulations within the ET-5 complex, characterized by particular housekeeping and antigen gene alleles. The Worcester isolates belonged to one of these subpopulations, the Stroud isolates belonged to another, and at least one representative of the third subpopulation identified in this work was isolated elsewhere in the United Kingdom. The sequence data demonstrated that ET-5 variants have arisen by multiple complex pathways involving the recombination of antigen and housekeeping genes and de novo mutation of antigen genes. The data further suggest that either the ET-5 complex has been in existence for many years, evolving and spreading relatively slowly until its disease-causing potential was recognized, or it has evolved and spread rapidly since its first identification in the 1970s, with each of the subpopulations attaining a distribution spanning several continents.

Amino Acid Sequence↗

Importance of intracranial atherosclerotic disease in patients with symptomatic stenosis of the internal carotid artery. The North American Symptomatic Carotid Endarterectomy Trail.

BACKGROUND AND PURPOSE: The estimated prevalence of intracranial atherosclerotic disease (IAD) in patients with stenosis of the extracranial internal carotid artery (ICA) varies between 20% and 50%. The benefits of carotid endarterectomy (CE) in patients with both IAD and symptomatic extracranial ICA stenosis are uncertain. METHODS: The association between IAD and other vascular risk factors and with the risk of stroke at 3 years were studied in patients with symptomatic extracranial ICA stenosis who participated in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Since the NASCET protocol excluded severe IAD, only a modest number of patients in this category could be studied. RESULTS: IAD was observed in one third of the patients. In medically treated patients, the relative risk of stroke associated with IAD varied from 1.3 (95% CI, 0.9 to 1.9) with extracranial ICA stenosis of <50% to 1.8 (95% CI, 1.1 to 3.2) with 85% to 99% ICA stenosis. In contrast, IAD did not affect the risk of stroke among surgically treated patients. To prevent 1 stroke ipsilateral to the symptomatic ICA stenosis over 3 years in patients who have also IAD, 12 patients with 50% to 69%, 5 patients with 70% to 84%, and 3 patients with 85% to 99% ICA stenosis have to undergo CE. In patients without IAD these numbers are 26, 7, and 6, respectively. CONCLUSIONS: IAD is an independent risk factor for subsequent stroke in medically treated patients with symptomatic ICA stenosis. CE reduces this risk. The additional risk imposed by IAD in medically treated patients enhances the value of CE in patients with moderate symptomatic extracranial ICA stenosis. Detection of IAD, requiring angiography, is an important prelude to planning CE in symptomatic patients with moderate extracranial ICA stenosis.

Aged↗

Evaluation of early computed tomographic findings in acute ischemic stroke.

BACKGROUND AND PURPOSE: Detection of large, hypoattenuated brain-tissue volume on hyperacute CT scan has been suggested as an exclusion criterion for early intravenous tissue plasminogen activator (IV-tPA) treatment. This study assessed the reliability of detection for these findings and their relationship to outcome. METHODS: Fifty hyperacute CT scans (<6 hours after ictus) were selected from a randomized trial evaluating IV-tPA (ATLANTIS trial). Three neuroradiologists blinded to all clinical information evaluated scans for degree of MCA territory involvement (<33% or >33%) and the presence of a hyperdense MCA. Evaluations were compared with 24-hour scan results, 30-day infarct volumes, and baseline NIH stroke scale scores (NIHSS). RESULTS: Readers reliably evaluated the degree of MCA territory hypodensity (intraclass correlation=0.53, P<0.001), with all 3 readers agreeing in 36 of 50 cases (72%). They correctly called >33% involvement with a sensitivity of 60% to 85% and a specificity of 86% to 97%. The baseline NIHSS was higher when >33% MCA hypodensity was seen (P=0. 021). Detection of significant hypodensity (>33%) correlated with poorer outcome. When >33% hypodensity was not detected, mean 30-day infarct volumes were 27.0 to 33.0 cm3, versus 84.3 to 123.1 cm3 when >33% hypodensity was present (P=0.002). CONCLUSIONS: Detection of MCA territory hypodensity on hyperacute CT scans is a sensitive, prognostic, and reliable indicator of the amount of MCA territory undergoing infarction.

Acute Disease↗

Contribution of bradykinin B(1) and B(2) receptors in allergen-induced bronchial hyperresponsiveness.

Bradykinin (BK) is a peptide mediator generated at sites of inflammation and its effects are mediated through constitutively expressed B(2) receptor or through induction of B(1) receptors. We examined the role of these receptors in bronchial hyperresponsiveness (BHR). Brown-Norway rats sensitized with ovalbumin (OA) and Al(OH)(3) intraperitoneally, were exposed 3 wk later to either saline or OA aerosol. B(1) receptor antagonist desArg(10)[Hoe140] (200 nmol/kg or 1 micromol/kg, intraperitoneally) or B(2) receptor antagonist Hoe140 (200 nmol/kg, intraperitoneally) was administered 30 min before allergen exposure. Hoe140 had no effect on OA-induced BHR to acetylcholine (ACh) and bronchoalveolar lavage fluid (BALF) cellular profiles, but inhibited bronchoconstriction to BK (p < 0.04). At both doses, desArg(10)[Hoe140] dose-dependently inhibited allergen-induced BHR to ACh (p < 0.01), but had no effect on bronchoconstriction to BK or baseline ACh responsiveness. The inflammatory cells in BALF were not affected apart from reduced lymphocyte numbers at the highest dose. B(1) receptor mRNA expression measured by Northern analysis was increased after allergen exposure in sensitized lungs, with a peak at 2 to 6 h after exposure, whereas B(2) receptor mRNA expression remained unchanged. Newly induced BK B(1) receptors may be involved in allergen-induced BHR to ACh, whereas constitutive B(2) receptors mediate BK-induced bronchoconstriction.

Acetylcholine↗

Flagellin gene polymorphism analysis of Campylobacter compared with antigen serotyping.

Flagellin gene sequence polymorphisms were used to discriminate amongst 53 strains of Campylobacter jejuni and C. coli. The Campylobacter strains were made up of forty-three strains of Campylobacter jejuni and 10 strains of Campylobacter coli. The results were analysed in relation to Penner serotyping. Twenty DNA PCR-RFLP patterns (genotypes) were identified by analysis of Dde I fragment length polymorphisms in flagellin gene (fla A and fla B) polymerase chain reaction (PCR) products. Flagellin gene 13 genotype was a feature of 15% of strains, followed by flagellin gene 8 (9%). Differences in fragment patterns were observed not only between members of two species, but also between individual strains of the same species. The strains that were non-typable by the Penner serotype were distributed into 6 flagellin gene types. In conclusion, Ddc I fla typing is reproducible and offers high typability. However, when the scheme is used in combination with the Penner serotype it provides improved discrimination for the characterizing and subtyping of isolates.

Animals↗

Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up. METHODS: Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis (ipsilateral) within 180 days before study entry were stratified according to the degree of stenosis (50 to 69 percent or <50 percent) and randomly assigned either to undergo carotid endarterectomy (1108 patients) or to receive medical care alone (1118 patients). The average follow-up was five years, and complete data on outcome events were available for 99.7 percent of the patients. The primary outcome event was any fatal or nonfatal stroke ipsilateral to the stenosis for which the patient underwent randomization. RESULTS: Among patients with stenosis of 50 to 69 percent, the five-year rate of any ipsilateral stroke (failure rate) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically (P=0.045); to prevent one ipsilateral stroke during the five-year period, 15 patients would have to be treated with carotid endarterectomy. Among patients with less than 50 percent stenosis, the failure rate was not significantly lower in the group treated with endarterectomy (14.9 percent) than in the medically treated group (18.7 percent, P=0.16). Among the patients with severe stenosis who underwent endarterectomy, the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent; this rate increased to only 6.7 percent at 8 years. Benefit was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms. CONCLUSIONS: Endarterectomy in patients with symptomatic moderate carotid stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke. Decisions about treatment for patients in this category must take into account recognized risk factors, and exceptional surgical skill is obligatory if carotid endarterectomy is to be performed. Patients with stenosis of less than 50 percent did not benefit from surgery. Patients with severe stenosis (> or =70 percent) had a durable benefit from endarterectomy at eight years of follow-up.

Aged↗

False positive diagnosis of meningococcal infection by the IS1106 PCR ELISA.

At a time when optimal case ascertainment for meningococcal infection is a high priority, the need for non-culture case confirmation, in particular by DNA amplification, is seen as being of vital importance to assist contact management and cluster recognition. A solution hybridisation assay with colorimetric microtitre plate detection (polymerase chain reaction-enzyme-linked immunosorbent assay (PCR ELISA)¿ has been developed using the multicopy insertion sequence IS1106 which had reportedly achieved a specificity of 100% and was described as being meningococcal specific. This PCR ELISA assay was evaluated on specimens from over 5000 patients at the national Meningococcal Reference Unit (MRU) between late 1995 and early 1997 and was found to be highly sensitive. Insertion sequences, however, are genetically mobile with the ability to spread between species and even genera. During the evaluation period of the IS1106 PCR ELISA a number of false positives proved to be caused by organisms other than N. meningitidis were recorded resulting in the withdrawal of this assay as a front line screening assay for routine confirmation of meningococcal infection.

Bacteriological Techniques↗

siaD PCR ELISA for confirmation and identification of serogroup Y and W135 meningococcal infections.

Non-culture diagnosis and serogroup determination of meningococcal infection is important in contact management where vaccination may be possible. A serogroup B and C PCR ELISA assay for the non-culture diagnosis and serogroup determination has proved invaluable for enhanced epidemiological surveillance and contact management. A polymerase chain reaction assay, based on a restriction fragment length polymorphism in the meningococcal serogroup Y and W135 sialyltransferase (siaD) gene, was developed to enhance the range of non-culture diagnosis of meningococcal infection from clinical samples. The PCR assay was adapted to an ELISA format incorporating hybridisation with serogroup-specific Y and W135 oligonucleotide probes. The serogroup-specific W135 and Y PCR ELISA is a useful addition to currently available serogroup B and C assay for non-culture diagnosis of meningococcal infection and outbreak investigation.

Enzyme-Linked Immunosorbent Assay↗

A reverse transcriptase polymerase chain reaction assay for the detection of thermophilic Campylobacter spp.

A novel method was developed for the detection of thermophilic enteropathogenic campylobacters based on the detection of mRNA using the reverse transcriptase polymerase chain reaction (RT-PCR). The RNA extraction method, DNase treatment and RT-PCR assay were shown to be specific for mRNA. The assay is specific for the thermophilic campylobacters Campylobacter jejuni, Campylobacter coli and Campylobacter upsaliensis and restriction fragment length polymorphism (RFLP) analysis of the 256 bp amplified product with the restriction endonucleases Alu I, Dde I and Dra I revealed distinct species specific patterns. The assay was applied to the detection of C. jejuni cells killed by heating at 72 degreesC for 5 min and mRNA was detected by RT-PCR immediately after heat killing but became undetectable within 4 h when the cells were held at 37 degreesC. The assay therefore can differentiate between viable and dead cells of C. jejuni.

Campylobacter↗