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Biomedical subjects

Alan Murray

Publications and source records attributed to Alan Murray.

12 recordsLinked to original sources

Age-related changes in the characteristics of the photoplethysmographic pulse shape at various body sites.

It is accepted that older subjects have increasing arterial stiffness resulting in changes in the propagation of the pulse to the periphery, and thereby influencing the peripheral pulse timing and shape characteristics. However, this age association with pulse shape is less clear in younger subjects and for different peripheral measurement sites. The aim of this study was to determine the association between age and changes in pulse shape characteristics at the ears, fingers and toes. Photoplethysmography pulse waveforms were recorded non-invasively from the right and left sides at the ears, index fingers and great toes of 116 normal healthy human subjects. Their median age was 41 years (range 13-72) allowing four distinct age groups to be considered (subjects younger than 30 years, 30-39 years, 40-49 years and 50 years of age or older). Normalized ear, finger and toe pulse shapes were calculated, for the whole subject group, and for the subjects within each age group. The differences in shape, relative to the oldest group, were also calculated for two distinct regions of interest: the systolic rising edge and the dicrotic notch of the pulse. Subtle, gradual and significant changes in the pulse shape were found at all sites with overall elongation of the systolic rising edge (p < 0.05) and damping of the dicrotic notch (p < 0.05) with age. The overall age-related changes in multi-site PPG pulse shape characteristics at the ear, finger and toe sites have been demonstrated and quantified. Age-matched normal ranges must be considered when evaluating pulses from patients with possible vascular disease.

Adolescent↗

Tuberculosis in seals caused by a novel member of the Mycobacterium tuberculosis complex: Mycobacterium pinnipedii sp. nov.

A comparison of Mycobacterium tuberculosis complex isolates from seals (pinnipeds) in Australia, Argentina, Uruguay, Great Britain and New Zealand was undertaken to determine their relationships to each other and their taxonomic position within the complex. Isolates from 30 cases of tuberculosis in six species of pinniped and seven related isolates were compared to representative and standard strains of the M. tuberculosis complex. The seal isolates could be distinguished from other members of the M. tuberculosis complex, including the recently defined 'Mycobacterium canettii' and 'Mycobacterium caprae', on the basis of host preference and phenotypic and genetic tests. Pinnipeds appear to be the natural host for this 'seal bacillus', although the organism is also pathogenic in guinea pigs, rabbits, humans, Brazilian tapir (Tapirus terrestris) and, possibly, cattle. Infection caused by the seal bacillus is predominantly associated with granulomatous lesions in the peripheral lymph nodes, lungs, pleura, spleen and peritoneum. Cases of disseminated disease have been found. As with other members of the M. tuberculosis complex, aerosols are the most likely route of transmission. The name Mycobacterium pinnipedii sp. nov. is proposed for this novel member of the M. tuberculosis complex (the type strain is 6482(T)=ATCC BAA-688(T)=NCTC 13288(T)).

Animals↗

Origin on the electrocardiogram of U-waves and abnormal U-wave inversion.

AIMS: Soon after the initial development of electrocardiography, U-waves were discovered in many normal subjects following the T-wave repolarisation waveform on the electrocardiogram. Various explanations have been offered for their origin, but none is universally accepted. We used our model of left ventricular repolarisation to explore the most common hypotheses for the genesis of U-waves. METHODS: Recently, we have shown that a computer model of left ventricular repolarisation was able to explain the formation of the characteristic shape of the T-wave, and we have now used this model to explore the most common hypotheses for the genesis of U-waves. The repolarisation phase of the action potentials in the model exhibited an after-potential. We investigated separately the effect on the 12-lead electrocardiogram of three different features of the model: the amplitude of the after-potential; dispersion of repolarisation in the left ventricle ranging from 20 to 100 ms; the timing of the after-potential, relative to the end of the principal action potential component, ranging from -100 to 100 ms. RESULTS: We show that delaying repolarisation in different regions of the heart cannot explain the U-wave, but show that the presence of after-potentials on the cardiac action potential do explain the U-wave polarity and other characteristic U-wave features. We also show that abnormal after-potential timing corresponds with abnormal U-wave inversion. CONCLUSION: Our model provides a realistic and simple solution to the problem of U-wave genesis.

Action Potentials↗

The forgotten Korotkoff phases: how often are phases II and III Present, and how do they relate to the other Korotkoff phases?

BACKGROUND: There are no data on the pattern of the Korotkoff phases in the normal population. This study was designed to describe the pattern of Korotkoff phase distribution in adults and children; to measure the duration of each of the phases; and to describe the differences between adults and children. METHODS: A total of 57 children (7 to 8 years old) and 59 adults (median age 47 years, range 30 to 62 years) were studied. The pressure in the arm cuff was deflated using a device to provide a consistent deflation rate. The Korotkoff sounds were recorded to MiniDisc from the bell of a stethoscope and each sound described as phase I, II, III, or IV. RESULTS: The most common pattern of Korotkoff phase distribution was for all five phases to be present (children [23/57; 40%], adults [24/59; 41%]). Phases I and IV were more common in children than in adults (56/57 [98%] v 47/59 [80%]; P = .002 for phase I; 52/57 [91%] v 44/59 [75%]; P = .018 for phase IV). Phases II and III were less common in children than in adults (32/57 [56%] v 50/59 [85%], P = .001 for phase II; 27/57 [47%] v 45/59 [76%], P = .001 for phase III). Phases I and IV were longer in children (median 3.9 [interquartile range, IQR 2.1 to 6.7] and 6.7 [IQR 3.2 to 9.8] sec, respectively) compared with adults (1.3 [IQR 0.7 to 2.7] and 1.7 [IQR 0.3 to 2.6), P < .001). CONCLUSIONS: There are clear differences in the Korotkoff phases between adults and children. The length of phases II and III increase with age with concomitant decrease in phases I and IV. These differences between adults and children remain unexplained.

Adult↗

Errors in repolarization measurement using magnetocardiography.

Multichannel magnetocardiography (MCG) noninvasively measures variations in magnetic field strength from many sites at the body surface, potentially providing useful regional information about ventricular repolarization. MCGs contain features similar to ECGs, and although errors associated with repolarization measurement have been quantified for ECGs, no comparative data exists for MCGs. In this study, errors in manual measurement of repolarization interval in the MCG were determined. Sixteen MCG channels and three ECG leads were recorded simultaneously in eight healthy subjects. Each recording was displayed in a random order on a computer screen, in presentations with different noise levels, time display widths, and amplitude display heights. In total, manual measurement of repolarization intervals in 2,048 (eight subjects x 16 channels x eight presentations x two repeats) MCGs were made by each of four analysts. Measured repolarization intervals were reduced by 3 ms when noise was added and by a further 3 ms when this noise was doubled. Intervals were shortened by 9 ms when the time display width was doubled and by a further 10 ms when the display width was doubled again. Measurements increased by 7 ms for a doubling of amplitude display height, equivalent to a doubling of T wave height. There were also consistent differences between analysts; amounting to a greatest mean difference of 24 ms. Display characteristics, added noise, and different analysts thus affect manual repolarization interval measurements in MCG. The errors detected demonstrate the importance of a standard presentation for repolarization measurement in the MCG.

Electrocardiography↗

Quantification of T wave shape changes following exercise.

T wave shape is increasingly used to provide insights into cardiac repolarization and, although shape is known to change as heart rate changes, there are no published quantitative clinical data. The aim of this study was to quantify these changes. Heart rate (HR), T wave amplitude, and two measures of T wave symmetry (SRarea--ratio of areas about the peak, SRtime--ratio of centrality of peak), were quantified over a period of 360 seconds following exercise in 20 healthy human subjects. As HR decreased, in all subjects the T wave became more asymmetrical (SRarea 20/20, SRtime 20/20, P < 0.0001). Resting reference HR and symmetry ratios were (mean +/- SD), HR 63 +/- 10 beat/min, SRarea 1.68 +/- 0.25, and SRtime 2.13 +/- 0.39. Fifty seconds postexercise, HR was significantly higher than reference at 92 +/- 11 beat/min (P < 0.0001), and symmetry ratios were significantly less at SRarea 1.04 +/- 0.15, SRtime 1.24 +/- 0.36 (P < 0.0001). Significant differences in HR and both symmetry ratios remained at 300 seconds postexercise. Amplitude increases had returned to their reference values at 300 seconds. T wave shape was significantly more symmetrical at higher HRs. These findings confirm qualitative reports of shape changes.

Adult↗

Effect of changes in heart rate and in action potential duration on the electrocardiogram T wave shape.

The mechanisms responsible for changes in T wave symmetry and amplitude with changes in heart rate and action potential duration were investigated. A computer model of normal left ventricular repolarization was used to simulate the T waves on the surface 12-lead ECG. The effect of heart rate changes was studied by varying the ratio between dispersion of repolarization (Disp) and action potential repolarization duration (APRD). With constant dispersion. as heart rate increases, APRD decreases and the ratio Disp/APRD increases. T waves were simulated while varying the Disp/APRD ratio from 3.6% to 100%. The T wave symmetry ratio measured from the areas either side of the peak (SRarea), the symmetry ratio from the times either side of the peak (SRtime) and the T wave amplitude (Tamplitude) were calculated from each simulated ECG. SRarea decreased from 1.42 to 0.77, SRtime from 1.75 to 1.04 and the Tamplitude increased from 0. 19 mV to 2.30 mV. The stability of results with variation in model characteristics was also investigated, by moving the heart +/- 20 mm on all three axes, rotating the heart axes by +/- 10 and by modifying all constants defining the action potential by +/- 5% and +/- 10%. T wave amplitude was sensitive to changes in heart position, as the heart was moved towards the body surface. However, T wave shape changed very little with heart position or rotation, with the SD of SRarea varying by less than 0.05 over an SRarea range of 0.65 for different values of Disp/APRD ratio. We have shown from our model that cardiac T waves increase in amplitude, and become more symmetric with their peaks becoming central as APRD shortens with increasing heart rate, agreeing with clinical observations. These results help to explain the T wave shape changes which occur when heart rate increases.

Action Potentials↗

Microvascular blood flow and skin temperature changes in the fingers following a deep nspiratory gasp.

The aims of this study were to quantify the changes in finger pulp skin temperature, laser Doppler flow (LDF, microvascular flux) and photoplethysmogram (PPG, microvascular blood volume pulsatility), induced by a deep inspiration in healthy subjects, and to investigate the repeatability of these responses within a measurement session and between measurement sessions on separate days. A system comprising an electronic thermometer, a laser Doppler flowmeter and a PPG amplifier measured simultaneous vasoconstrictor responses to a deep inspiratory gasp from three adjacent fingers of one hand. Clearly defined responses were obtained in 15 of the 17 subjects studied. Skin temperature fell in all of these subjects after each gasp, with a median fall of 0.089 degrees C (P < 0.001). The median value of LDF flux reduction was 93% (P < 0.001) indicating a momentary almost complete shut-down of microvascular blood flow; and PPG also showed a large response relative to pulse amplitude of 2.6 (P < 0.001). The median times for waveforms to reach their minimum were 4.6 s (PPG), 6.3 s (LDF) and 29.1 s (skin pulp temperature), with median delays between minima of LDF and PPG of 1.6 s (P < 0.001) and skin temperature and PPG of 23.5 s (P < 0.001). The vascular responses of skin temperature, LDF and PPG to an inspiratory gasp were repeatable, with temperature change repeatable to within 10% of the median subject change.

Adult↗

Fractal analysis in the detection of colonic cancer images.

The aim of this study was to investigate the value of fractal dimension in separating normal and cancerous images, and to examine the relationship between fractal dimension and traditional texture analysis features. Forty-four normal images and 58 cancer images from sections of the colon were analyzed. A "leave-one-out" analysis approach was used to classify the samples into each group. With fractal analysis there was a highly significant difference between groups (p < 0.0001). Correlation and entropy features showed greater differences between the groups (p < 0.0001). Nevertheless, the addition of fractal analysis to the feature analysis improved the sensitivity from 90% to 95% and specificity from 86% to 93%.

Case-Control Studies↗

Identification of an immunogenic 18-kDa protein of Helicobacter pylori by alkaline phosphatase gene fusions.

The use of alkaline phosphatase fusion methodology to identify Helicobacter pylori exported proteins enabled the identification of an open reading frame (ORF) encoding a highly immunogenic, previously uncharacterised exported protein. The predicted aminoacid sequence displays a typical N-terminal signal peptide and contains regions of C-terminal hydrophobicity consistent with a membrane-associated protein. Southern blot analysis revealed that the gene encoding the protein was absent in several Helicobacter spp. and a combination of PCR and sequence analysis of the amplified gene showed that it is highly conserved amongst isolates of H. pylori. To obtain pure recombinant protein, the gene encoding the protein was cloned and expressed as a beta-galactosidase (beta-gal) fusion in Escherichia coli and the protein was purified by affinity chromatography and proteolytic cleavage of the beta-gal portion. The purified protein, which has an apparent mol. wt of 18 kDa, was recognised by antibody present in 71% of sera from patients infected with H. pylori, but in only 16% of sera from patients with unrelated or no gastrointestinal disease, by Western blot assays. These results indicate that the 18-kDa protein from H. pylori is immunogenic and is expressed in vivo.

Alkaline Phosphatase↗

A novel polymorphic genetic locus in members of the Mycobacterium tuberculosis complex.

It has previously been shown that the PAN promoter from Mycobacterium paratuberculosis can be used as a DNA probe to identify an RFLP between wild-type Mycobacterium bovis and the vaccine strain Mycobacterium bovis BCG. To investigate the genetic basis of this phenomenon, DNA fragments from a New Zealand M. bovis cattle strain and M. bovis BCG Pasteur, containing the PAN-binding region, were isolated from gene libraries, sequenced and characterized. Sequence analysis and comparison with database sequences showed that the PAN region in M. bovis, M. bovis BCG and Mycobacterium tuberculosis is identical and shares 70% similarity to the PAN sequence from M. paratuberculosis. The Shine-Dalgarno sequence and the -10 and -35 promoter regions are conserved between the different species. Analysis of the flanking sequences of the PAN region revealed that less than 1 kb downstream of PAN is a 2405 bp fragment that is present in M. bovis BCG but absent in the M. bovis wild-type strain. The distribution of the 2405 bp fragment in members of the M. tuberculosis complex was investigated and found to be present in 70 out of 70 M. tuberculosis strains, and 7 out of 7 M. bovis BCG daughter strains, 2 out of 2 Mycobacterium africanum strains, 2 out of 2 Mycobacterium microti strains and 7 out of 25 M. bovis strains. This is the first report of a genetic region of M. bovis BCG that is not universally present in M. bovis strains. The fragment does not appear to be present in any mycobacterial species outside the M. tuberculosis complex. It does not possess any characteristics of known transposable elements and the flanking sequences do not have any obvious features to suggest a deletion mechanism. The genetic location of this region is close to the 3' end of the RD1 region of M. bovis and M. tuberculosis. The polymorphic nature of this locus in M. bovis will provide an additional genetic marker for strain differentiation.

Amino Acid Sequence↗