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Biomedical subjects

A Murray

Publications and source records attributed to A Murray.

At least 217 records · Page 12Linked to original sources

Assessing ECG signal quality on a coronary care unit.

Poor electrocardiograph (ECG) signal quality is associated with an increase in the number of false alarms, may degrade diagnostic information, and can increase the workload for coronary care unit (CCU) or other intensive care staff. It is important therefore to establish simple quantitative measures that can be used to demonstrate signal quality problems. In this study, a fixed-gain diagnostic bandwidth ECG from patients in a single CCU bed was monitored continuously for 10 weeks and measures which could relate to quality were calculated. These measures were the number of times the ECG exceeded a preset limit (out-of-range events, +/-4 mV) and the frequency content of the ECG plus superimposed noise in six different bandwidths (0.05-0.25, 0.25-10, 10-20, 20-48, 48-52, and 52-100 Hz). A computer-based data collection system calculated a 10 s average for each of the measures and logged these to memory. Following the data collection phase, good-quality baseline levels for the seven measures were calculated for each of the days studied and compared with levels during the evening-night (6 pm-6 am), which were in turn compared with levels during the day-time (6 am-6 pm). All measures were significantly lower (p < 0.001) for the selected good-quality ECGs compared with those recorded during the night, with low frequency, lower ECG bandwidth, and out-of-range events producing the greatest differences. Night-time noise levels were lower than day-time levels, and the largest reductions were found in the rate of out-of-range events (19.8 to 9.3 h-1) (p < 0.02), and low-frequency content less than 0.25 Hz (70 to 56 microV) (p < 0.01). Significant reductions during the night were also found in the lower ECG bandwidth 0.25-10 Hz (111 to 98 microV) (p < 0.01). No significant changes were found in the higher frequencies. We conclude that the low-frequency content and rate of out-of-range events are easy to obtain and could be used as measures for evaluating signal quality.

Coronary Care Units↗

Haplotype and interspersion analysis of the FMR1 CGG repeat identifies two different mutational pathways for the origin of the fragile X syndrome.

To understand the origins of the fragile X syndrome and factors predisposing alleles to instability and hyperexpansion, we have compared the haplotype (using markers FRAXAC1, FRAXAC2, and DXS548) and AGG interspersion patterns of the FMR1 CGG repeat for 214 normal and 16 premutation chromosomes. Association testing between interspersion pattern and haplotype reveals a highly significant (P < 0.002) non-random distribution, indicating that all three markers are useful in phylogenetic reconstruction of mutational change. Parsimony analysis of the FMR1 CGG repeat substructure predicts that loss of AGG interruptions has occurred independently on many haplotypes associated with the fragile X syndrome, partially explaining the haplotype diversity of this disease. Among haplotypes found in linkage disequilibrium with the fragile X mutation, two different modes of mutation and predisposition to instability have been identified. One pathway has involved the frequent and recurrent loss of AGG interruptions from rare asymmetrical ancestral array structures. Intergenerational transmission studies suggest that these predisposed chromosomes progress relatively rapidly to the disease state. In contrast, the second mutational pathway involves a single haplotype which has maintained two AGG interruptions. Parsimony analysis of CGG repeat substructure within this haplotype suggests that larger alleles have been generated by gradual increments of CGG repeats distal to the most 3' interruption. Pedigree analysis of the intergenerational stability of alleles of this haplotype confirms a gradual progression toward instability thresholds. As a result, a large reservoir of chromosomes carrying large repeats on this haplotype exists. These chromosomes are predisposed to disease. The present data support a model in which there are at least two different mutational pathways predisposing alleles to instability and hyperexpansion associated with the fragile X syndrome.

Alleles↗

Population screening at the FRAXA and FRAXE loci: molecular analyses of boys with learning difficulties and their mothers.

Preliminary results on a large population-based molecular survey of FRAXA and FRAXE are reported. All boys with unexplained learning difficulties are eligible for inclusion in the study and data are presented on the first 1013 tested. Individuals were tested for the number of trinucleotide repeats at FRAXA and FRAXE and typed for four flanking microsatellite markers. Mothers of 760 boys were tested to determine the stability of the FRAXA and FRAXE repeats during transmission and to provide a population of control chromosomes. The frequency of FRAXA full mutations was 0.5%, which gives a population frequency of 1 in 4994, considerably less than previous reports suggest. No FRAXE full mutations were detected, confirming the rarity of this mutation. In the boys' X chromosomes, we detected one FRAXA premutation with 152 repeats and one putative FRAXE premutation of 87 repeats. No full or premutations were seen in the control chromosomes. A significant excess of intermediate alleles at both FRAXA and FRAXE was detected in the boys' X chromosomes by comparison with the maternal control chromosomes. This suggests that relatively large unmethylated repeats of sizes 41-60 for FRAXA and 31-60 for FRAXE may play some role in mental impairment. No instability was found in transmissions of minimal or common alleles in either FRAXA or FRAXE, but we saw two possible instabilities in transmission of FRAXA and two definite instabilities in transmission of FRAXE among 43 meioses involving intermediate or premutation sized alleles. We found no linkage disequilibrium between FRAXA and FRAXE but did find significant linkage disequilibrium between large alleles at FRAXE and allele 3 at the polymorphic locus DXS1691 situated 5 kb distal to FRAXE.

Adolescent↗

Automated recognition of EEG changes accompanying arousal in respiratory sleep disorders.

Daytime sleepiness and impaired cognitive function can be a consequence of recurrent transient arousal from sleep, associated with abrupt changes in the electroencephalogram (EEG). EEG is normally assessed by trained observers from paper records, but automation offers the advantages of speed and objectivity. We assessed 10 automated indices of EEG activity as potential indicators of arousal. Arousals from light, slow wave and rapid eye movement sleep were studied in 30 subjects. Segments of EEG recorded immediately before and after each arousal were analyzed by automated measurement of 10 EEG indices using a personal computer. We investigated the ability of each index to recognize arousal while rejecting change due to variability during sleep. Nine of the 10 indices showed significant changes with arousal (p < 0.001); the better indices were related to EEG frequency, and 3 were chosen for further study. In these indices, the mean changes with arousal were 3.8 Hz (ZeroCross), 1.7 Hz (Hjorth's Mobility) and 1.2 Hz (FrqMean, an index of central EEG frequency). With none of these three indices were significant differences in performance due to base sleep stage or subject group found. We conclude that detection of arousal is feasible using automated methods that measure simple indices related to the frequency of the EEG waveform.

Adult↗

Accuracy of four automatic QT measurement techniques in cardiac patients and healthy subjects.

OBJECTIVE: To assess differences in the accuracy of automatic QT measurement in three subject groups, and to determine the influence of T wave amplitude on these measurements. SUBJECTS: Standard simultaneous 12 lead electrocardiograms were acquired from 25 patients post myocardial infarction, 25 with arrhythmias, and 25 controls. DESIGN: Because there is not yet a standard automatic method for QT analysis, four different techniques were used. Manual QT measurements were used as the reference. QT was measured in two complexes by each technique in each lead, subject, and group. MAIN OUTCOME MEASURE: The differences between reference and automatic QT measurements from the three subject groups were compared independently for the four techniques. The T wave amplitudes for each of the groups were also compared. RESULTS: Variability of the automatic QT measurements, relative to the manual reference, in the cardiac patients was 2.1 times that in the controls (P < 0.005). Mean T wave amplitude was lower (by a factor of two) for the cardiac patients compared with the controls (P < 0.01). No simple relation between T wave amplitude and the difference between automatic and manual QT measurements was found, although the difference was 2.2 times greater for absolute T wave amplitudes of less than 0.25 mV (P < 0.001). CONCLUSIONS: Automatic QT measurement techniques are less accurate in cardiac patients than in controls. Measurements from T waves with amplitudes less than 0.25 mV are less reliable.

Arrhythmias, Cardiac↗

Comparison of lower limb arterial assessments using color-duplex ultrasound and ankle/brachial pressure index measurements.

The strength of agreement between two noninvasive methods of assessing lower limb arterial disease and their relationship to patient symptoms following exercise have been investigated. Color-duplex ultrasound (CDU) and ankle/brachial pressure index (ABPI) (before and afer exercise) measurements were obtained from 200 consecutive patients referred to a vascular investigations laboratory. From these patients, 290 limbs were available for study, comprising limbs without previous vascular surgery, from patients without diabetes and who could attempt a walking exercise test. The overall level of agreement between CDU and resting ABPI measurements was 83% (Kappa 0.66). The ABPI technique identified the more serious disease; a resting ABPI of less than 0.6 gave 100% agreement with CDU. With higher resting ABPIs the level of agreement became poorer: 83% (0.6 < or = ABPI <0.9) and 76% (normal ABPI > or = 0.9). The addition of postexercise ABPI measurements in determining significant arterial disease increased the strength of relationship between the two techniques by only 2% (85%, Kappa 0.69). The exercise test was generally limited by the most symptomatic limb in each patient, and the agreement between CDU and postexercise ABPI measurements in these limbs was higher at 93% (Kappa 0.81). In comparison, agreement for the least symptomatic group of limbs was found to be poor (69%, Kappa 0.37). Compared with symptoms after exercise, overall agreements with CDU and ABPI were both 67% (Kappa 0.27). The agreement was better (91%) when the resting ABPI was less than 0.6. The ABPI is biased toward the detection of more severe disease and is more consistent with CDU when the most symptomatic limbs are compared. The relationship between either test and symptoms after exercise is strong only for limbs with major disease.

Adult↗

Measurement of the vestibulo-ocular reflex by magnetometry during active head movement.

A new method of measuring the vestibulo-ocular reflex (VOR) during active head movements is presented. Subjects sat and attempted to maintain their gaze upon a fixed point whilst turning their heads from side to side in response to an auditory cue, to attain frequencies of head rotation that increased from 1 Hz to 4 Hz during a 24 s period. Head movements were monitored by a small magnetic field detector worn on the subject's forehead and positioned a set distance from a magnetic field transmitter coil. Eye movements were monitored using the corneo-retinal potential. Gain (eye angle/head angle) and phase difference (eye phase-head phase) were calculated to define the VOR. Three repeat measurements were made on 20 normal subjects. Gain decreased significantly (P < 0.0001) with increasing frequency whilst the phase difference remained unchanged. The 95% prediction intervals were narrow for both gain (+/- 0.28) and phase (+/- 11 degrees). These data, together with the speed and ease of performance of the test, suggest that the test can provide valuable information on the performance of the vestibular system.

Adult↗

Angioplasty pressure-volume measurement.

An instrument has been developed for controlled inflation and deflation of an angioplasty balloon. The mean difference between inflation to 800 kPa in air and a simulated coronary artery is 71.2 kPa. The repeatability of four inflation/deflation cycles is 6.4 kPa with the balloon in air and 9.0 kPa in the simulated artery.

Angioplasty, Balloon, Coronary↗

Responses of bovine T cells to fractionated lysate and culture filtrate proteins of Mycobacterium bovis BCG.

Bacterial cell lysates and culture filtrate proteins of Mycobacterium bovis BCG were each separated in a two-dimensional system that yields soluble protein fractions immediately available for probing with T cells. The fractions were used in lymphocyte proliferation assays using blood lymphocytes from cattle immunized with either viable or gamma-irradiated BCG. Cattle immunized with either form of BCG responded similarly to fractionated lysate proteins. Cattle immunized with viable BCG responded to culture filtrate proteins that were not recognized by cattle immunized with dead BCG. Marked heterogeneity of the responses to the culture filtrate proteins was seen.

Animals↗

Assessment of the ventricular fibrillation detection algorithm in the semi-automatic Cardio-Aid defibrillator.

The sensitivity and specificity of ventricular fibrillation (VF) detection in the semi-automatic Cardio-Aid defibrillator was assessed with 25 ECG recordings, each of length 40 s. Of the 25 ECG recordings, 12 contained VF requiring defibrillation, 3 contained a tachyarrhythmia with a waveform similar to VF but which self-terminated, and 10 were selected from abnormal rhythms and artefacts which contained some features similar to VF. Sensitivity was assessed from the VF data. Specificity was assessed from both the rhythm preceding VF or the tachyarrhythmias, and from the VF-like data. The response to a changing rhythm was assessed from the self-terminating tachyarrhythmias. Each recording was replayed to the defibrillators at 3 signal amplitudes (normal, half and double). Request to analyse the ECG because of possible VF and advice to shock were noted separately. The sensitivity for recommending a shock when a shock was required was 92%. The sensitivity for drawing attention to VF, through requesting analysis was 97%. There were no false detections in the rhythms preceding VF or the tachyarrhythmias (specificity with good quality signals 100%). The specificity with the VF-like data ws 90%. There was significant difference between this defibrillator and other semi-automated defibrillators previously assessed.

Algorithms↗

Assessment of five serum marker assays in patients with advanced breast cancer treated with medroxyprogesterone acetate.

This study concerns five different tumour marker assays examined in the context of 94 patients with advanced breast cancer treated in a prospectively randomised trial of different doses of medroxyprogesterone acetate (MPA). MPA was administered at doses of 500 or 1000 mg daily and clinical evaluation of patients was carried out according to UICC criteria. Carcinoembryonic antigen (CEA) was selected as a standard marker, with three assays for MUC1 mucins (epithelial mucin core antigens (EMCA), EMCA2 and BR-MA immunoradiometric assay) differing in antibody specificities for different mucin epitopes. An additional novel assay for soluble cytokeratin was also evaluated as an example of an independent marker with a different nature and biology. Sensitivity of individual assays ranged between 44 (EMCA2) and 69% (cytokeratin) and the use of two assays in combination led to sensitivities as high as 84% (cytokeratin+BR-MA). The proportion of patients found to be assessable by each assay ranged between 51 (EMCA2) and 76% (cytokeratin). Of those patients whose marker changes were assessable, those receiving the higher dose of MPA displayed significant falls in marker levels after 12 weeks of treatment. This effect was not observed in patients receiving 500 mg. The change in cytokeratin levels in patients undergoing high dose MPA therapy proved to be most marked. Using the cytokeratin assay, 91% (of 23 patients) of patients with progressive disease showed at least a 25% rise in serum marker levels. Of these, 66% showed increases before disease progression was detected clinically with a mean lead time of 14 weeks. There was very little difference between the responses of the five tumour marker assays in patients with stable or responding disease, the proportion of these patients with stable or falling tumour marker levels ranging between 58% (CEA) and 77% (EMCA). We conclude that the cytokeratin assay has an application in monitoring response to therapy and predicting tumour progression in advanced breast cancer patients with assessable tumour marker profiles, especially if used in combination with a MUC1 mucin assay.

Adult↗

Prospective assessment of an artificial neural network for the detection of peripheral vascular disease from lower limb pulse waveforms.

The diagnostic performance of an artificial neural network pulse classification system for the detection of peripheral vascular disease was investigated prospectively. Lower limb photoelectric plethysmographic pulses, and Doppler ankle/brachial pressure index (ABPI) measurements (pre- and post-exercise) were obtained from 200 patients referred to a vascular investigation laboratory. A single toe pulse was processed and used as input data to a neural network which had been trained previously with a set of pulses from 100 legs. The neural network outputs represented the diagnostic arterial disease classifications defined by the ABPI. From the 200 patients entered prospectively, 266 legs were available for neural network assessment. A network sensitivity of 92% and specificity of 63% were achieved with a diagnostic accuracy of 80%. By using a higher confidence for the classification decision a small, but insignificant overall improvement was obtained. When a borderline classification was introduced 100% sensitivity and 100% negative predictive value were obtained, though 31% of legs were unclassifiable. Nevertheless, the very high sensitivity and negative predictive value could make this quick and simple technique the one of choice for the first stage in screening large numbers of subjects.

Adult↗

Variation in the identification of Q wave initiation and its contribution to QT measurement.

Cardiac repolarization abnormalities can be assessed from measurements of the QT duration taken from paper electrocardiogram recordings. Errors associated with determining the end of the T wave are known, but those associated with the start of the Q wave have so far been neglected. This paper quantifies the variation in manual identification of the start of the Q wave, and assesses its contribution to errors in the manual measurement of QT. A randomized study of errors in the timing of Q wave initiation from electrocardiograms plotted on paper was conducted. Four electrocardiogram leads were recorded in eight subjects relaxing in a semi-recumbent position. Manual measurements were made of the time of Q wave initiation in 512 electrocardiograms, presented with different superimposed noise, recording speed and recording gain. The greatest mean difference between four cardiologists amounted to 6.7 ms. A recording gain of 5 mm mV-1, in comparison with 10 mm mV-1, resulted in a difference in Q wave timing of 3.2 ms (P < 0.05). A further increase in gain, or the addition of noise up to 20 microV made no significant difference to Q wave measurements. Provided ECGs of at least 10 mm mV-1 are used, the effect of variation in Q determination on QT measurement is likely to be small.

Electrocardiography↗

Measurement of baroreflex gain from heart rate and blood pressure spectra: a comparison of spectral estimation techniques.

The baroreflex is the physiological control system linking blood pressure and heart rate. Baroreflex gain, alpha, can be estimated from the ratio of heart rate and blood pressure spectra. The aim of this study was to quantify differences in estimates of alpha incurred by using four different spectral analysis techniques. ECG and blood pressure were recorded from 10 healthy subjects. Spectra were estimated using fast Fourier transform (FFT), zero-padded FFT (FFTZ), FFT of the windowed autocovariance function (ACVF), and maximum-entropy (ME) methods. For each subject a mean value of alpha was calculated in the MF (0.05-0.15 Hz) and HF (0.15-0.35 Hz) bands. Mean alpha MF varied between subjects (range 2-10 ms mmHg-1) as did mean alpha HF (range 4-12 ms mmHg-1). Mean differences in alpha MF and alpha HF estimated with different techniques were small. Differences in alpha MF ranged from 0.074 ms mmHg-1 (FFTZ against ME) to 0.298 ms mmHg-1 (FFT against ACVF) and those in alpha HF ranged from 0.057 ms mmHg-1 (FFT against FFTZ) to 0.342 ms mmHg-1 (ACVF against ME). None of these differences were significant. The use of different spectral analysis techniques does not significantly affect estimates of alpha.

Aged↗

Objective features of the surface electrocardiogram during ventricular tachyarrhythmias.

The aim of this study was to quantify the electrocardiographic signal characteristics of three types of ventricular arrhythmia; monomorphic ventricular tachycardia, polymorphic ventricular tachycardia and ventricular fibrillation. Patients in a coronary care unit were monitored using a single bipolar ECG lead. Thirty episodes of ventricular tachyarrhythmia (ten from each group) were recorded automatically by computer. Frequency analysis of ten consecutive 1 s epochs from each recording gave 100 spectra for each tachyarrhythmia group. Each spectrum was characterised by the frequency, there were significant differences in all characteristics between the tachyarrhythmia groups (P<0.025). Ventricular fibrillation had a higher mean dominant frequency (4.8 Hz) than polymorphic ventricular tachycardia (3.7 Hz) and monomorphic ventricular tachycardia (3.8 Hz). The dominant frequency of ventricular fibrillation was also more variable than that of monomorphic ventricular tachycardia (P<0.01). Mean peak size was largest for monomorphic ventricular tachycardia (0.78) and smallest for ventricular fibrillation (0.64). The single spectral peaks seen throughout this study indicate that all three tachyarrhythmias have an underlying periodic mechanism. The differences in spectral characteristics show that varying degrees of myocardial electrical organisation can be quantified from surface ECG features.

Electrocardiography↗