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Biomedical subjects

R M Harrison

Publications and source records attributed to R M Harrison.

At least 37 records · Page 2Linked to original sources

Measuring extraocular muscle volume using dynamic contours.

The effect of medical treatment on extraocular muscle enlargement in thyroid associated ophthalmopathy (TAO) may be monitored by measuring the change in volume of the extraocular muscles on serial orbital MRI examinations. In theory, 3D image sets offer the opportunity to minimise errors due to poor repositioning and partial volume effects. This study describes an automated technique for estimating extraocular muscle volumes from 3D datasets. Operator input is minimal and the technique is robust. Verification of the technique on both simulated and real datasets is described. For simulated image sets, both automated segmentation and manual outlining produced estimates of volume which were on average 4% less than "true" volume. For real patient data, extraocular muscle volumes measured by the automated technique were 1.6% (SD 13%) less than volumes measured by manual outlining. Coefficient of variation for repeat outlining of the same image dataset for the automated technique was 1.0%, compared with 4% for manual outlining. The manual technique took an experienced operator approximately 20 min to perform, compared to 7 min for the automated technique. The automated method is therefore rapid, reproducible and at least as accurate as other available methods.

Algorithms↗

Particulate matter and daily mortality and hospital admissions in the west midlands conurbation of the United Kingdom: associations with fine and coarse particles, black smoke and sulphate.

OBJECTIVES: There is considerable evidence linking ambient particles measured as particulate matter with aerodynamic diameter <10 microm (PM(10)) to daily mortality and hospital admissions but it is not clear which physical or chemical components of the particle mixture are responsible. The relative effects of fine particles (PM(2.5)), coarse particles (PM(2.5-10)), black smoke (mainly fine particles of primary origin) and sulphate (mainly fine particles of secondary origin) were investigated, together with ozone, SO(2), NO(2), and CO, on daily mortality and hospital admissions in the west Midlands conurbation of the United Kingdom. METHODS: Time series of health outcome and environmental data were obtained for the period 1994-6. The relative risk of death or hospital admission was estimated with regression techniques, controlling for long term time trends, seasonal patterns, influenza epidemics, effects of day of the week, and temperature and humidity. Models were adjusted for any remaining residual serial correlation and overdispersion. The sensitivities of the estimates for the effects of pollution to the inclusion of a second pollutant and seasonal interactions (warm or cool) were also examined. RESULTS: Daily all cause mortality was not associated with any gaseous or particulate air pollutant in the all year analysis, although all measures of particles apart from PM(2.5-10) showed significant positive effects of the warm season. Neither respiratory nor cardiovascular admissions (all ages) were associated with any air pollutant, and there were no important seasonal interactions. However, analysis of admissions by age found evidence for various associations-notably between PM(10), PM(2.5), black smoke, SO(2,) and ozone (negative) and respiratory admissions in the 0-14 age group. The coarse fraction, PM(2.5-10) differed from PM(2.5) in having smaller and less consistent associations (including several large significant negative associations) and a different lag distribution. The results for black smoke, an indicator of fine primary carbonaceous particles, were very similar to those for PM(2.5), and tended to be more robust in two pollutant models. The effects of sulphate, an indicator of secondary particles, also showed some similarities to those of PM(2.5). CONCLUSIONS: Clear effects of air pollution on mortality and hospital admissions were difficult to discern except in certain age or diagnostic subgroups and seasonal analyses. It was also difficult to distinguish between different measures of particles. Within these limitations the results suggest that the active component of PM(10) resides mostly in the fine fraction and that this is due mainly to primary particles from combustion (mainly vehicle) sources with a contribution from secondary particles. Effects of the coarse fraction cannot be excluded.

Adolescent↗

The effect of exposure to sulphuric acid on the early asthmatic response to inhaled grass pollen allergen.

Particulate sulphates, including sulphuric acid (H2SO4), are important components of the ambient aerosol in some areas and are regarded as air pollutants with potentially important human health effects. Challenge studies suggest little or no effect of H2SO4 exposure on lung function in asthmatic adults, although some epidemiological studies demonstrate an effect of acid species on symptoms in subjects with asthma. To date, the effect of H2SO4 on allergen responsiveness has not been studied. The effect of exposure to particulate H2SO4 on the early asthmatic response to grass pollen allergen has been investigated in 13 adults with mild asthma. After establishment of the provocative dose of allergen producing a 15% fall in forced expiratory volume in one second (FEVI) (PD15) for each subject, they were exposed to air, 100 microg m(-3) or 1,000 g x m(-3) H2SO4 for 1 h, double-blind in random order > or =2 weeks apart, through a head dome delivery system 14 h after each exposure subject underwent a fixed-dose allergen challenge (PD15). Ten subjects completed the study. The mean early asthmatic responses (maximum percentage change in FEV1 during the first 2 h after challenge) following air, 100 microg x m(-3) H2SO4, and 1,000 microg m(-3) H2SO4, were -14.1%, -16.7%, and -18.4%, respectively. The difference between 1,000 microg x m(-3) H2SO4 and air was significant (mean difference: -4.3%, 95% confidence interval (CI: -1.2-7.4%, p=0.013). The difference between air and 100 microg m(-3) H2SO4 approached significance (mean difference: -2.6%, 95% CI: 0.0-5.3%, p = 0.051). These results suggest that, at least at high mass concentration, sulphuric acid can potentiate the early asthmatic response of mild asthmatic subjects to grass pollen allergen, although the effect is limited.

Administration, Inhalation↗

The effect of sulphur dioxide exposure on indices of heart rate variability in normal and asthmatic adults.

Sulphur dioxide (SO2) is an important air pollutant and causes bronchoconstriction in normal and asthmatic adults. This paper has explored the autonomic consequences of SO2 exposure using the spectral analysis of heart rate variability. Electrocardiogram recordings were made in 12 normal and 12 asthmatic adults undergoing pollutant exposures. Exposures were of a 1 h duration, double blind, in random order, > or = 2 weeks apart and included air and 200 parts per billion SO2. Spectral analysis of R-R intervals was performed. SO2 exposure was associated with an increase in total power (TP) and high (HF) and low frequency (LF) power in the normal subjects, and a reduction in these indices in the subjects with asthma. The difference in TP with SO2 exposure compared to air was +1730 ms2 in the normal group and -1021 ms2 asthmatic group (p<0.003). For HF the respective values were +964 ms2 and -539 ms2 (p=0.02) and for LF, +43 7 ms2 and -57 2 ms2 (p=0.01). No change in lung function or symptoms was observed in either group. This suggests that SO2 exposure at concentrations which are frequently encountered during air pollution episodes can influence the autonomic nervous system. This may be important in understanding the mechanisms involved in SO2 induced bronchoconstriction, and of the cardiovascular effects of air pollution.

Adult↗

Particulate matter in the atmosphere: which particle properties are important for its effects on health?

Whilst epidemiological studies have consistently demonstrated adverse effects of particulate matter exposure on human health, the mechanism of effect is currently unclear. One of the major issues is whether the toxicity of the particles resides in some particular fraction of the particles as defined by chemical composition or size. This article reviews selected data on the major and minor component composition of PM2.5 and PM10 particulate matter showing quite major geographic variations in composition which are not reflected in the exposure-response coefficients determined from the epidemiology which show remarkably little spatial variation. The issue of particle size is more difficult to address due to the scarcity of data. Overall, the data presented provides little support for the idea that any single major or trace component of the particulate matter is responsible for the adverse effects. The issue of particle size is currently unclear and more research is warranted.

Acids↗

Secondary reduction in calpain 3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies).

Dysferlin is the protein product of the gene (DYSF) that is defective in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy. Calpain 3 is the muscle-specific member of the calcium activated neutral protease family and primary mutations in the CAPN3 gene cause limb girdle muscular dystrophy type 2A. The functions of both proteins remain speculative. Here we report a secondary reduction in calpain 3 expression in eight out of 16 patients with a primary dysferlinopathy and clinical features characteristic of limb girdle muscular dystrophy type 2B or Miyoshi myopathy. Previously CAPN3 analysis had been undertaken in three of these patients and two showed seemingly innocuous missense mutations, changing calpain 3 amino acids to those present in the sequences of calpains 1 and 2. These results suggest that there may be an association between dysferlin and calpain 3, and further analysis of both genes may elucidate a novel functional interaction. In addition, an association was found between prominent expression of smaller forms of the 80 kDa fragment of laminin alpha 2 chain (merosin) and dysferlin-deficiency.

Calpain↗

Identification of SIV env-specific CTL in the jejunal mucosa in vaginally exposed, seronegative rhesus macaques (Macaca mulatta).

We previously reported major histocompatibility complex Class I-restricted cytotoxic T lymphocytes (CTL) in jejunal lamina propria (LP) of monkeys following colonic exposure to subinfectious SIV doses. Those monkeys with strong mucosal CTL responses specific for simian immunodeficiency virus (SIV) envelope (env) were protected from later colonic challenge with a heterologous pathogenic virus dose. Here, env-specific CTL were similarly induced in jejunal LP in five of eight non-progesterone treated macaques that were vaginally exposed to SIV, but not infected. Subsequent vaginal challenge following progesterone treatment produced systemic infection. The only two monkeys that had jejunal env-specific CTL detectable post-challenge developed significantly lower plasma virus loads, and had delayed disease progression. Either vaginal or colonic exposure to subinfectious SIV doses can induce CTL detectable in jejunal LP. The association of such CTL with protection or delayed disease upon challenge suggests that successful vaccine protection against SIV/HIV may require CTL responses in the mucosa.

Animals↗

Impact of correcting peak flow for nonlinear errors on air pollutant effect estimates from a panel study.

Air pollutant effects are commonly investigated using panel studies employing daily measurement of changes in peak expiratory flow (PEF). Variable orifice PEF meters are inaccurate with a nonlinear relationship to actual PEF. The impact on a panel study of correcting these errors was examined. Twice-daily PEF readings were taken by 147 9-yr old children for 8 weeks and corrected using an equation derived from the response of 32 Vitalograph meters to a servomechanism-controlled pump. Pollutant effect estimates for corrected and uncorrected readings were derived using a regression approach incorporating appropriate confounders. Correction impacted little on mean PEF values (333.1-334.2 L x min(-1)), but did alter effect sizes. Nonsignificant nitrogen dioxide estimates for the entire panel decreased by up to 73%, but, for symptomatic/atopic children, a significant 5-day mean result was lost (decrease in effect size from -2.53 to -0.90% per 10 parts per billion (ppb)) and lag 0 became significant (decrease from -0.51 to -1.22% per 10 ppb). Mass concentration estimates of particles with a 50% cut-off aerodynamic diameter of 2.5 microm moved in both directions (-0.22 changed to 0.11% per 10 microg x m(-1) lag 3 and -0.29 to -0.73% per 10 microg x m(-3) for the 5-day mean). Correction of nonlinearity of peak expiratory flow meters influenced the overall outcome of this panel study, and the changes in effect estimates would be sufficient to alter the interpretation of some studies. For adults, a greater change in effect estimates may follow the larger correction required for their usual peak expiratory flow range.

Adult↗

Quality assurance for MRI: practical experience.

The aim of this study is to propose guidelines for quality assurance (QA) in MRI, based on a comprehensive assessment of QA parameters undertaken on a busy clinical MRI scanner over the course of 1 year. QA phantoms supplied by the scanner manufacturer were used together with the Eurospin MRI phantom set. Signal-to-noise ratio (SNR) and image uniformity were measured daily from spin echo images acquired using a quadrature send-receive head coil and from a gradient echo sequence using the Helmholtz body coil. The voltage of the transmit radiofrequency (RF) amplifier was noted. Monthly measurements of slice thickness, geometric distortion, slice position, image resolution and image ghosting were acquired using the head coil. In addition, SNR was measured monthly on a selection of commonly used coils. Apart from some drift of the RF amplifier voltage, all measurements were within acceptable limits and were stable over the course of 1 year. Satisfactory measurements of SNR were possible using the simple phantom supplied with the scanner. The SNR, geometric distortion and RF amplifier voltage are simple to determine and can be measured in less than 15 min by the scanner operator, using the scanner software. Weekly recording of these parameters is recommended for busy clinical MRI scanners, as this should allow deviations from acceptable limits to be identified early. Such in-house checks can usefully be compared with the less frequent estimations performed by the service engineer. Comprehensive QA routines are discussed for systems used for quantitative measurements.

Electricity↗

Personal exposures to airborne metals in London taxi drivers and office workers in 1995 and 1996.

In 1995, a petroleum marketer introduced a diesel fuel additive in the UK containing Mn as MMT (methylcyclopentadienyl manganese tricarbonyl). A small study of personal exposures to airborne Mn in London was conducted before and after introduction of the additive to identify any major impact of the additive on exposures. In 1995, personal exposures to Mn were measured in two groups, taxi drivers and office workers (10 subjects per group) for two consecutive 7-day periods. A similar study was carried out in 1996 to determine if exposures had changed. Samples were also analyzed for Ca, Al, Mg and Pb. In 1996, exposures to aerosol mass as total suspended particulates (TSP) and PM2.5 were measured in addition to the metals. Manganese exposures in this cohort did not increase as a result of introduction of the additive. However, a significant source of Mn exposure was discovered during the conduct of these tests. The mean exposure to Mn was higher among the office workers in both years than that of the taxi drivers. This was due to the fact that approximately half of the office workers commuted via the underground railway system where airborne dust and metal concentrations are significantly elevated over those in the general environment. Similar results have been noted in other cities having underground rail systems. Exposure to Mn, Pb, Ca, and Mg were not significantly different between the 2 years. Taxi drivers had higher exposures than office workers to Mg and Pb in both years. Commuting via the underground also had a significant impact on exposures to TSP, PM2.5, Al, and Ca, but had little effect on exposures to Mg. The aerosol in the underground was particularly enriched in Mn, approximately 10-fold, when compared to the aerosol in the general environment. There are several possible sources for this Mn, including mechanical wear of the steel wheels on the steel rais, vaporization of metal from sparking of the third rail, or brake wear.

Air Pollutants, Occupational↗

Partial volume effects in MRI studies of multiple sclerosis.

We have estimated the accuracy of volume measurements of multiple sclerosis (MS) lesions made using magnetic resonance imaging (MRI) for lesions of comparable diameter to the image slice thickness. We used a phantom containing objects of known volume and obtained images using a range of slice thicknesses. Measurements on the phantom were used to assess a theoretical model, which was then employed to investigate the effects of image dimensions and geometry upon volume measurement accuracy. We observed measured volume to be dependent upon slice thickness. Thin slices gave the most accurate estimate of volume. As slice thickness increased relative to object diameter, the error in the volume measurement increased (to as much as 100%), the volume measured being dependent on the position of the object relative to the slice center. Using a signal intensity threshold value of 50% to outline objects gave results closest to the actual volume. As expected, a lower threshold value tended to give higher volume estimates (up to 100% larger), as did a semi-automated local edge detection technique. For accurate volume measurement, the slice thickness should be no more than a fifth of anticipated object diameter. For typical MS lesions (7 mm in diameter), this implies using a 1.5-mm slice thickness. For serial studies, a repositioning error of 1 mm could lead to differences in the volume measurement of individual lesions of up to 12% between studies for lesions of typical MS size and 5-mm slice thickness. These results emphasize the need for accurate patient repositioning, relatively thin slices, for regular quality assurance checks to ensure that pixel size and slice position are correct and stable over time, and that lesion outlining is performed in a consistent fashion. We would recommend the use of a 3D sequence with 1 mm cubic voxels for accurate measurements of MS lesions.

Humans↗

Patient dosimetry measurement methods.

This article reviews patient dosimetry measurement methods applied to diagnostic radiology examinations. Various dose quantities and their relevance to patient dose surveys are described. When contemplating a patient dose survey it is important to develop a clear measurement strategy. This involves a detailed consideration of the most applicable dose measurement method for the intended survey. Various approaches to patient dosimetry are described and reviewed.

Data Collection↗

Development of a personal monitoring method for nitrogen dioxide and sulfur dioxide with Sep-Pak C18 cartridge sampling and ion chromatographic determination.

Personal monitoring methods for the determination of hourly integrated concentrations of NO2 and SO2 in ambient air have been developed. Triethanolamine (TEA)-impregnated C18 Sep-Pak cartridges were used to collect NO2 and SO2 simultaneously. After sampling, NO2 and SO2 as their nitrite, nitrate, sulfite and sulfate analogues were stripped from the cartridges with a solution of 5% methanol in distilled, deionized water (DDW) and then determined by ion chromatography. Laboratory tests were conducted to evaluate the sampling rate, collection and recovery efficiencies, breakthrough volumes, absorption capacity, interference and sample stability on the cartridge during storage. NO2 and SO2 detection limits of 0.3 and 0.4 ppb respectively for 1 h samples were obtained. Recoveries for both NO2 and SO2 exceeded 85%.

Air Pollutants↗

A comparison of two methods for measuring the signal to noise ratio on MR images.

The signal to noise ratio (SNR) is one of the important measures of the performance of a magnetic resonance imaging (MRI) system. The object of this study was to compare a single acquisition method, which estimates the noise from background pixels, with a dual acquisition method which estimates the noise from the subtraction of two sequentially acquired images. The dual acquisition method is more exact, but is slower to perform and requires image manipulation. A comparison between the two methods gave a good correlation, and a regression equation of SNRsingle = 1.1 + 0.94 SNRdual. The single acquisition method is therefore appropriate for use in a quality assurance programme, since it is quicker and simpler to perform and is a good indicator of the more exact measure.

Magnetic Resonance Imaging↗

Bladder infection in the menopausal monkey.

PURPOSE: The highest incidence of urinary tract infection in females occurs in elderly women. This study was done to determine whether this is due to the declining immune response that occurs during advancing age, or the menopausal state in the aged. MATERIALS AND METHODS: Adult female monkeys (average age 19 years) were studied, half being subjected to bilateral oophorectomy to produce the menopause. In addition, old females (average age 29 years) already at menopause were studied before and after hormonal replacement with estradiol and progesterone. Bacterial adherence to vaginal cells was studied prior to and after urethral infection with E. coli. Plasma estradiol and progesterone levels were done, as well as white blood counts, plasma cytokine assays and serum antibody titers. RESULTS: Bacteriuria was not prolonged, nor was there a significant difference in bacterial adherence to vaginal cells due to menopause. Interleukin-1 levels were depressed after surgical menopause but not as much as found in the old menopausal females and this low level was not corrected by hormonal replacement. The initial interleukin-2 levels were higher after spontaneous menopause, but the increasing plasma levels seen in cycling animals after infection did not occur in the aged menopausal females following infection even after hormone replacement. The antibody titers to the E. coli infection showed a trend to a lessened response to infection after menopause but were not significantly decreased. CONCLUSIONS: The deficient Il-1, Il-2 and antibody response following infection was not corrected by hormone replacement and thus appears to be due to aging rather than lack of female hormones. These facts may be explained by the T cell senescence known to occur in aged individuals.

Age Factors↗

Effect of genistein on steroid hormone production in the pregnant rhesus monkey.

Genistein is a phytoestrogen found in soy beans. Phytoestrogens have been reported to cause reproductive problems in sheep and rats. This research was conducted to determine the effects of genistein fed to rhesus monkeys during pregnancy, with specific interest on fetal growth and steroidogenesis in the maternal-fetoplacental unit. Two groups of five monkeys each were selected in early stages of pregnancy. One group was administered genistein in a fruit treat each weekday until Cesarean section 10 days prior to term. The second, control group, received fruit treats without genistein. Maternal blood samples were collected on Tuesday and Friday of each week. At delivery, samples were collected from the maternal peripheral circulation, uterine veins, uterine-ovarian veins, and the fetal heart. Comparisons between control and genistein-treated monkeys revealed no differences in the maternal weight gained during pregnancy, or in fetal weights or placental weights at delivery. Serum was assayed by radioimmunoassay (RIA) for estradiol, progesterone, dehydroepiandrosterone sulfate (DHEA-S), and estrone. No significant differences (P > 0.05) were noted in progesterone or DHEA-S levels at delivery or during the pregnancy; however, estradiol levels were higher (P < 0.05) in the four areas studied at delivery and in the maternal blood with advancing gestation. Additionally, estrone levels tended to increase more rapidly (P = 0. 057) in the maternal blood of monkeys receiving genistein than in untreated controls, suggesting that genistein may stimulate the deconjugation of estrone in the gut, thus allowing its reabsorption into the peripheral circulation and conversion to estradiol.

Animals↗

Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations.

OBJECTIVES: To investigate whether there is an excess of leukaemias in 0-15 year old children among those living in close proximity (within 100 m) of a main road or petrol station. METHODS: Data for 0-15 year old children diagnosed between 1990 and 1994 in the United Kingdom West Midlands were used. Postcode addresses were used to locate the point of residence which was compared with proximity to main roads and petrol stations separately, and to both together. Odds ratios (ORs) were calculated with solid tumours as a control, and incidence ratios (IRs) with population density as a control. RESULTS: The method based on solid tumours as a control showed ORs of 1.61 (95% confidence interval (95% CI) 0.90 to 2.87) and 1.99 (95% CI 0.73 to 5.43), for those living within 100 m of a main road or petrol station respectively. When population was used as a control, the estimated IRs for leukaemia were 1.16 (95% CI 0.74 to 1.72) and 1.48 (95% CI 0.65 to 2.93) for residence within 100 m of a main road or petrol station respectively, but neither reached significance at the 95% level. Results for residence in close proximity to both a main road and petrol station were inconsistent, but there were few. The influence of socioeconomic factors as represented by the Townsend deprivation index on leukaemia incidence was not significant and the results were not explicable on the basis of impact of social class. CONCLUSIONS: The results are suggestive of a small increase in risk of childhood leukaemia, but not solid tumours, for those living in close proximity to a main road or petrol station. This increase in risk is not, however, significant and a larger study is warranted to establish the true risk and causes of any increase in risk.

Adolescent↗

Effect of age and hormonal state on cytokine synthesis in the monkey.

The authors studied plasma cytokine activity using cross reactive polyclonal antibodies to human cytokines in young and old female monkeys to determine if age had any effect on cytokine secretion, and compared hormonal effects as well. While interleukin 1 (IL-1) was not higher in aged cycling monkeys, it was after menopause. Menopause depressed IL-2 activity also. Variable results were seen with the other cytokines.

Aging↗