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Biomedical subjects

D Buchanan

Publications and source records attributed to D Buchanan.

At least 19 recordsLinked to original sources

Why is mortality higher in Scotland than in England and Wales? Decreasing influence of socioeconomic deprivation between 1981 and 2001 supports the existence of a 'Scottish Effect'.

OBJECTIVES: To determine the degree to which changing patterns of deprivation in Scotland and the rest of Great Britain between 1981 and 2001 explain Scotland's higher mortality rates over that period. DESIGN: Cross-sectional analyses using population and mortality data from around the 1981, 1991 and 2001 censuses. SETTING: Great Britain (GB). PARTICIPANTS: Populations of Great Britain enumerated in the 1981, 1991 and 2001 censuses. MAIN OUTCOME MEASURES: Carstairs deprivation scores derived for wards (England and Wales) and postcode sectors (Scotland). Mortality rates adjusted for age, sex and deprivation decile. RESULTS: Between 1981 and 2001 Scotland became less deprived relative to the rest of Great Britain. Age and sex standardized all-cause mortality rates decreased by approximately 25% across Great Britain, including Scotland but mortality rates were on average 12% higher in Scotland in 1981 rising to 15% higher in 2001. While over 60% of the excess mortality in 1981 could be explained by differences in deprivation profile, less than half the excess could be explained in 1991 and 2001. After adjusting for age, sex and deprivation, excess mortality in Scotland rose from 4.7% (95% CI: 3.9% to 5.4%) in 1981 to 7.9% (95% CI: 7.2% to 8.7%) in 1991 and 8.2% (95% CI: 7.4% to 9.0%) in 2001. All deprivation deciles showed excess indicating that populations in Scotland living in areas of comparable deprivation to populations in the rest of Great Britain always had higher mortality rates. By 2001 the largest excesses were found in the most deprived areas in Scotland with a 17% higher mortality rate in the most deprived decile compared to similarly deprived areas in England and Wales. Excess mortality in Scotland has increased most among males aged <65 years. CONCLUSIONS: Scotland's relative mortality disadvantage compared to the rest of Great Britain, after allowing for deprivation, is worsening. By 1991 measures of deprivation no longer explained most of the excess mortality in Scotland and the unexplained excess has persisted during the 1990s. More research is required to understand what is causing this 'Scottish effect'.

Adolescent↗

Dust concentrations and respiratory risks in coalminers: key risk estimates from the British Pneumoconiosis Field Research.

To help inform the setting of dust control standards in coalmines, this brief review summarises the most recent and reliable exposure-response relations, for damaging respiratory effects, derived from the Pneumoconiosis Field Research (PFR). Collecting data over 38 years in the British coal industry, this was a programme of prospective research on the respiratory health of coal miners, characterised by regular health surveys and detailed measurements of dust and silica concentrations in the workplace. Exposure-response relations are presented for coal workers' simple pneumoconiosis category II, progressive massive fibrosis, defined deficits of lung function (FEV1), and category II silicosis. This simplified overview provides a guide to the most recent and most reliable estimates from the PFR of dust-related risks of substantial pulmonary disease, and to the magnitude of the effects. Control of dust sufficient to prevent category II simple pneumoconiosis should prevent most cases of progressive massive fibrosis and most dust related large lung function deficits. Where the dust contains high proportions of silica, control to low levels is essential, and even quite brief excursions of silica to high levels must be avoided.

Adult↗

Influencing sceptical staff to become supporters of service improvement: a qualitative study of doctors' and managers' views.

OBJECTIVE: To explore scepticism and resistance towards changes in working practice designed to achieve service improvement. Two principal questions were studied: (1). why some people are sceptical or resistant towards improvement programmes and (2). what influences them to change their minds. METHODS: Semi-structured qualitative interviews were conducted with 19 clinicians and 19 managers who held national and regional roles in two national programmes of service improvement within the NHS involving systematic organisational changes in working practices: the National Booking Programme and the Cancer Services Collaborative (now the Cancer Services Collaborative Improvement Partnership). RESULTS: Scepticism and resistance exist in all staff groups, especially among medical staff. Reasons include personal reluctance to change, misunderstanding of the aims of improvement programmes, and a dislike of the methods by which programmes have been promoted. Sceptical staff can be influenced to become involved in improvement, but this usually takes time. Newly won support may be fragile, requiring ongoing evidence of benefits to be maintained. CONCLUSIONS: The support of health service staff, particularly doctors, is crucial to the spread and sustainability of the modernisation agenda. Scepticism and resistance are seen to hamper progress. Leaders of improvement initiatives need to recognise the impact of scepticism and resistance, and to consider ways in which staff can become positively engaged in change.

Evaluation Studies as Topic↗

Quantitative relations between exposure to respirable quartz and risk of silicosis.

AIMS: To reanalyse exposure-response data from a Scottish colliery to gain a more detailed knowledge of the relations between exposure to quartz and risks of silicosis in coal miners, and hence inform the debate on an appropriate occupational standard for respirable quartz. METHODS: Detailed data on working times at different quartz concentrations were combined to produce exposure profiles for miners who had provided a full chest radiograph at a follow up survey. Logistic regression methods were used to model profusion of radiographic abnormalities category 2/1+, and a general exposure index was used to compare different quartz exposure measures in these models. RESULTS: Results in 371 men aged 50-74 indicated that cumulative quartz exposure at higher concentrations resulted in proportionally greater risks of abnormalities. One g x h x m(-3) of cumulative exposure at quartz concentrations greater than 2 mg x m(-3) was estimated to have equivalent risks to 3 g x h x m(-3) at lower concentrations. The timing of exposure relative to follow up appeared less important, although the study had limited power to compare different lag periods between exposure and effect. CONCLUSIONS: Quantification of the risks of silicosis should take account of variations in quartz exposure intensity, particularly for exposure to concentrations of greater than 1 or 2 mg.m(-3), even if exposure is for relatively short periods. The risks of silicosis over a working lifetime can rise dramatically with even brief exposure to such high quartz concentrations. Risk estimates are given, to inform choice of control limits.

Aged↗

A clinical neurological, neurophysiological, and neuropsychological study of sheep farmers and dippers exposed to organophosphate pesticides.

OBJECTIVES: To classify clinical diseases of the subjects with abnormal indices of peripheral neuropathy identified in field studies of sheep farmers and dippers exposed to organophosphate pesticides. To explore what neuropsychological profiles, if any, may be associated with neurophysiological damage in these subjects. METHODS: A case-control study (79 subjects) nested within the cross sectional study (685 subjects) of sheep farmers from the field study. Three groups with no, possible, and probable or definite neuropathy according to field studies were recruited. Investigations comprised symptoms of neuropathy, neurologial signs, motor and sensory nerve conduction, electromyography, quantitative sensory testing, and neuropsychological tests. RESULTS: The incidence of clinical neuropathy increased from 7% in the no neuropathy group to 52% in the probable or definite neuropathy group based on nerve conduction measurements or presence of neurological signs. Sensory abnormalities were found more often than motor deficits. Small diameter nerve fibres were also affected more than large fibres. CONCLUSIONS: The neuropathy is predominantly sensory and is characteristic of distal, chronic neuropathy with no acute features. Small fibre populations are affected more than large fibre populations. Increasing severity of neuropathy was associated with anxiety and depression as measured in the neuropsychological tests.

Adolescent↗

Clinical validation of methods of diagnosis of neuropathy in a field study of United Kingdom sheep dippers.

OBJECTIVES: To investigate the reproducibility of measured indices of chronic peripheral neuropathy from a field study of sheep dippers when compared with similar measurements carried out in a clinical setting. METHODS: A stratified random sample of field study subjects was invited to attend a clinic. Neuropathy was measured both in the field and at the clinic with a modified version of a standard symptoms questionnaire and quantitative sensory thresholds for hot, cold, and vibration. These were combined into a classification of the likelihood of neuropathy with a neuropathy scoring system. Indicators of sensory abnormality were based on comparison of sensory thresholds to age dependent reference values derived from an external reference group. RESULTS: Only 51% of subjects were assigned similar classifications in the field and clinic based on the neuropathy scoring system. Of the component indices, grouped symptom scores, with 65% of subjects showing exact agreement, proved to be more reproducible than quantitative sensory test indicators. There were biases in the comparison of field and clinic measurements of hot and vibration sensations, but no evidence of greater variation between individual people in sensory thresholds in the field relative to at the clinic. CONCLUSIONS: The neuropathy scoring system proved to be of limited reproducibility, due in a large part to the lack of reproducibility of the indicators of sensory test abnormality caused by inadequate temperature control. However, the symptoms score and measured sensory thresholds could be used separately as indices of neuropathy in exposure-response analyses.

Adult↗

Retention and separation of adenosine and analogues by affinity chromatography with an aptamer stationary phase.

A biotinylated-DNA aptamer (molecular weight 16,600) that binds adenosine and related compounds in solution was immobilized by reaction with streptavidin, which had been covalently attached to porous chromatographic supports. The aptamer medium was packed into fused-silica capillaries (50-150-microm i.d.) to form affinity chromatography columns. Frontal chromatography analysis indicated that the dissociation constants (Kd) of cyclic-AMP, AMP, ATP, ADP, and adenosine were 138 +/- 18, 58 +/- 2, 38 +/- 2, 28 +/- 6 and 3 +/- 1 microM, respectively, for aptamer immobilized on a controlled pore glass support. Similar values were obtained for aptamer immobilized on a polystyrene support except for a slightly higher Kd for adenosine. The Kd for adenosine is similar to the previously reported value of 6 +/- 3 microM for adenosine-aptamer in solution indicating that immobilized aptamers can have affinity similar to that of the solution forms. Columns had 20 nmol of binding sites/100 microL of support media, which is 3.3-fold higher than that previously reported for immobilization of IgG on similar media, indicating that the aptamer can be immobilized with higher density than antibodies. Variation of mobile-phase conditions revealed that ionic strength and Mg2+ level had strong effects on retention of analytes while pH and buffer composition had less of an effect. It was demonstrated that the column could selectively retain and separate cyclic-AMP, NAD+, AMP, ADP, ATP, and adenosine, even in complex mixtures such as tissue extracts.

Adenosine↗

Estimation of cumulative exposure to organophosphate sheep dips in a study of chronic neurological health effects among United Kingdom sheep dippers.

OBJECTIVES: To derive a method for retrospectively estimating cumulative exposure to organophosphate (OP) pesticides among a cross section of United Kingdom sheep dippers, as part of a wider epidemiological study of neurological abnormality within this group of workers. METHODS: A hygiene study of dipping sessions at 20 farms using diazinon based dips was carried out by two experienced occupational hygienists. Observations on the exposure of people to concentrate and dilute dip were recorded throughout each dipping session, together with the other relevant factors including the use and condition of protective clothing. Concentrations of urinary metabolites of diazinon were used to measure actual exposure to OPs. To estimate exposure in the subsequent epidemiological study, an occupational exposure history questionnaire was developed using results from the hygiene study and an empirical exposure model. RESULTS: In the hygiene study, increased urinary metabolites were associated with the handling of concentrate dip and exposure to dilute dip wash through splashing. Very few dippers wore the recommended protective clothing. The handling of concentrate dip was the principal source of exposure to OPs. Dipping task was used as a surrogate for splashing of dilute dip in retrospective exposure estimation. In the epidemiological study, cumulative exposure to OP sheep dips was highly correlated with the total number of dipping days, but not with age. CONCLUSIONS: Sheep dip concentrate is the most important source of OP exposure among sheep dippers and estimates of exposure to OPs during routine dipping should take due account of exposure to concentrate dip as well as to the dilute dip wash. The observed use of recommended protective clothing by most subjects was insufficient to allow a proper empirical assessment of its effectiveness.

Agricultural Workers' Diseases↗

An epidemiological study of the relations between exposure to organophosphate pesticides and indices of chronic peripheral neuropathy and neuropsychological abnormalities in sheep farmers and dippers.

OBJECTIVES: To investigate the hypothesis that chronic low level exposure to organophosphates (OPs) in sheep dips is related to clinically detectable measures of polyneuropathy. METHODS: The design was a cross sectional exposure-response study of sheep dippers and other non-exposed groups. The study group consisted of 612 sheep dipping farmers, 53 farmers with no sheep dipping experience, and 107 ceramics workers. Retrospective exposure information was obtained by questionnaire based on stable and easily identifiable features of sheep dipping found during the first phase of the study; in particular, estimates of handling concentrate and splashing with dilute dip. Neurological assessments were based on a standard neuropathy symptoms questionnaire, and thermal and vibration quantitative sensory tests. RESULTS: Adjusted for confounders there was a weak positive association between cumulative exposure to OPs and neurological symptoms, the significance of which was dependent on the inclusion of a few individual workers with extremely high exposure. There was no evidence of an association between cumulative exposure and the thermal or vibration sensory thresholds. However, separating the effects of exposure intensity and duration showed a higher prevalence of symptoms, primarily of a sensory type, among sheep dippers who handled the OP concentrate. There was also evidence that sensory and vibration thresholds were higher among concentrate handlers, the highest exposed group of dippers. CONCLUSIONS: The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. There was only weak evidence of a chronic effect of low dose cumulative exposure to OPs. It is suggested that long term health effects may occur in at least some sheep dippers exposed to OPs over a working life, although the mechanisms are unclear.

Adolescent↗

A comparison of native tallgrass prairie and plains bluestem forage systems for cow-calf production in the southern great plains.

The objective of this study was to compare an introduced warm-season perennial grass (plains bluestem, Bothriochloa ischaemum) to native tallgrass prairie for cow-calf production. Three systems were used, two based on tallgrass prairie with two different forms of protein supplementation and one based on plains bluestem as the primary forage. The systems were as follows: 1) native tallgrass prairie with pelleted oilseed meal as the winter protein supplement (native-control); 2) native tallgrass prairie with limited access to wheat pasture as the winter protein supplement (native-wheat); and 3) plains bluestem with limited access to wheat pasture as the protein supplement (bluestem-wheat). Oilseed meal protein supplements were fed twice weekly. Cows grazing wheat pasture were allowed 6 h of grazing twice weekly. Ninety-nine cows per year were used over the 3-yr study. Cows were sired by either Charolais, Gelbvieh, Angus, or Hereford bulls out of commercial Angus-Hereford dams. Calves were sired by Simmental bulls. Calving and weaning rate increased over time but did not differ among systems or breed types. System did not influence the size or body condition score of cows or the performance of calves, but changes in the weight and condition scores of cows were greater on either native system than on the bluestem-wheat system. Cows from Charolais and Gelbvieh bulls were taller (P < 0.05), and heavier (P < 0.05), and weaned heavier (P < 0.05) calves than cows from Angus or Hereford bulls. The weight of cows on the bluestem-wheat system tended to decrease over time, whereas cows grazing on the native systems tended to gain weight over time. The native-control system was the most profitable system based on cow production. If excess hay produced from the bluestem-wheat system was sold as a cash crop, then this system was the most profitable. In general, we conclude that limit-grazing wheat pasture is a viable alternative to oilseed meal as protein supplement for wintering dry cows. Although the bluestem system had 2.5 times the carrying capacity of the native prairie systems, increased productivity was offset by increased production costs. All systems were equal on a cow basis for providing nutrients for the cow-calf production system.

Animal Feed↗

Distribution of atrophy in Helicobacter pylori-infected subjects taking proton pump inhibitors.

BACKGROUND: Gastric atrophy is associated with Helicobacter pylori infection. Conflicting results have been obtained as to whether acid suppressant therapy hastens the development or changes the distribution of atrophy in the stomach. The aim of this study was to investigate whether concomitant proton pump inhibitor (PPI) therapy in H. pylori-infected individuals resulted in an increase or an alteration in atrophy distribution and whether this was reflected by the plasma gastrin. METHODS: Multiple gastric biopsy specimens were taken from the antrum and corpus from 46 H. pylori-infected subjects, 18 of whom were taking PPIs, and assessed histologically by the updated Sydney System. The control group was age- and sex-matched to the index group. Fasting gastrin levels were measured. RESULTS: In the control group there was no significant tendency for either antral or corpus atrophy to predominate (P = 0.44). In the treatment group there was a significant tendency for corpus as opposed to antral atrophy to develop (P < 0.001). There was no significant difference in the overall atrophy score between the treated and untreated groups (P = 0.76). Fasting gastrin levels were significantly higher in the treated group (P < 0.001). CONCLUSIONS: Treatment with PPIs in H. pylori-infected subjects does not lead to an overall increase in gastric atrophy. It does, however, result in an increased prevalence of corpus as opposed to antral atrophy. This is associated with a significantly higher gastrin level.

Adult↗

Pathogenicity of a special-purpose glass microfiber (E glass) relative to another glass microfiber and amosite asbestos.

This article describes the activity of an E-glass microfiber (104E) during chronic inhalation and intraperitoneal injection studies in rats. Results are compared with another microfiber of similar dissolution rate (k(dis)), code 100/475, and the more durable amosite asbestos, both of which we had previously used in similar experiments (Davis et al., 1996). Rats were exposed to aerosol concentrations of 1000 fibers (longer than 5 microm)/ml, as measured by optical microscopy, for 7 h/day, 5 days/wk. Subgroups of rats were followed for mean lung burden, early and late signs of fibrosis, and tumor incidence. At the end of 12 mo of exposure, the mean number of 104E fibers of all lengths in the lungs was approximately double that for amosite but two-thirds of that for 100/475. For fibers longer than 15 microm, the mean 104E burden was similar to that for the amosite and more than twice that of the 100/475. After a 12-mo recovery period, the retained lung burdens (of fibers of all lengths) were approximately 30% of those at 12 mo for both microfibers, and somewhat higher (approximately 44%) for amosite. Amosite and 100/475 fibers longer than 15 microm were more persistent in the lungs than 104E fibers. The chemical composition of 104E fibers did not appear to have been significantly altered by up to 24 mo of residence in lung tissue, whereas the composition of 100/475 was substantially altered over the same time period. From the inhalation study, out of the pathology subgroup of 43 animals exposed to 104E microfibers, 10 had lung tumors (7 carcinoma, 3 adenoma) and 2 had mesotheliomas, whereas in 42 rats exposed to amosite asbestos, there were 16 lung tumors (7 carcinoma, 9 adenoma) and 2 mesotheliomas. The 104E- and amosite-treated animals had similar levels of fibrosis. In contrast, 38 animals treated with 100/475 had little fibrosis, 4 lung tumors (adenomas), and no mesotheliomas. The greater pathogenicity of the 104E fibers, compared to 100/475 fibers, might be partly explained by the greater numbers of long fibers retained in the lung after 12 mo of inhalation. However, we speculate that modification of surface properties by extensive selective leaching of some glass components reduces the toxic potential of 100/475. In a parallel intraperitoneal injection study, 104E caused considerably more mesotheliomas (21 rats out of 24) than 100/475 (8 rats out of 24). In addition, 104E appeared to be more active than amosite asbestos, since mesotheliomas appeared much more quickly in the 104E-treated animals. In conclusion, we have shown that two microfiber types, 100/475 and 104E, of similar dissolution rates, had markedly different pathogenicity in rats. We believe that this contrast is only partly due to differences in numbers of long fibers and that differences in surface properties of the fibers, possibly due to proportionately greater leaching of 100/475 fibers, play an important role.

Administration, Inhalation↗

Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure.

Results from animal studies have indicated some uncertainties over the validity of a single general occupational control limit for all types of "particulates (insoluble) not otherwise classified" (PNOC) (ACGIH, 2000). Therefore, to examine the extent to which a given control limit may be valid for nontoxic dusts with different physical characteristics, this study compared the pulmonary effects in rats of inhalation exposure to two poorly soluble dusts of similar density and with relatively low toxicity: titanium dioxide and barium sulfate. The objectives were to compare the dusts in (a) their buildup and clearance in the lungs during inhalation; (b) their transfer to lymph nodes; (c) the changes, with time, in the lavageable cell population; and (d) the pathological change from histology. The exposure aerosol concentrations were selected to achieve similar mass and volume lung burdens for both dusts and to attain "overload" over the common exposure periods of about 4 mo and 7 mo. Despite obtaining similar lung burdens for both dusts, there was significantly more translocation of TiO(2) to the hilar lymph nodes than with BaSO(4). It was also found that clearance of TiO(2) was retarded whereas clearance of BaSO(4) was not. Trends in these data were clarified by the use of a simple model of particle clearance. Retardation of particle clearance and translocation to the lymph nodes are markers of the condition known as "overload" in which the alveolar macrophage-based clearance of particles from the deep lung is impaired. In addition, bronchoalveolar lavage showed that TiO(2) caused significantly more recruitment of inflammatory neutrophils to lungs than BaSO(4). These differences between the dusts were not due to differences in toxicity, solubility, or lung deposition. The explanation that the different responses are due to the different particle size distributions of the two dust types is examined in a companion paper (Tran et al., this issue).

Administration, Inhalation↗

Inhalation of poorly soluble particles. II. Influence Of particle surface area on inflammation and clearance.

In this article the volumetric overload hypothesis, which predicts the impairment of clearance of particles deposited in the lung in terms of particle volume, is reevaluated. The degree to which simple expressions of retained lung burden explain pulmonary responses to overload was investigated using data from a series of chronic inhalation experiments on rats with two poorly soluble dusts, titanium dioxide and barium sulfate. The results indicated that the difference between the dusts in the level of inflammation and translocation to the lymph nodes could be explained most simply when the lung burden was expressed as total particle surface area. The shape of the statistical relationship for both lung responses indicated the presence of a threshold at approximately 200-300 cm(2) of lung burden. On the basis of this and other similar results, a hypothesis regarding a generic mechanism for the impairment of clearance and associated lung responses is proposed for such "low-toxicity" dusts.

Administration, Inhalation↗

Biopersistence and durability of nine mineral fibre types in rat lungs over 12 months.

The study objectives were to assess the ability of intratracheal injection methods to discriminate between nine fibre types in respect of pulmonary biopersistence, and to provide approximate estimates of relative biopersistence and durability for a study of general relationships with biological and toxicological responses. The test fibres included six samples of size-selected fibre types specially prepared for research purposes, two commercially available fibres, and amosite. A 1 mg dose of each fibre type was administered to rats by intratracheal injection. The relative biopersistence of fibres in different size categories was assessed from the changes in mean lung burden, as determined by electron microscopy, at 3 days and 1, 6 and 12 months after injection. The ability of the test materials to resist dissolution was measured in a parallel series of simple in vitro acellular experiments at two pHs and in a continuous flow dissolution test. The observed differences in the persistence of fibres of differing length recovered from rat lungs were consistent with the current hypothesis that short fibres are cleared by cellular processes and long fibres by dissolution and disintegration. Differences in persistence of long (> 20 microns) fibres were correlated with measured rates of dissolution in vitro. Differences in persistence among those fibre types also studied by others workers were consistent with their findings after inhalation and intratracheal injection. Overall, the differences in the biopersistences of the test fibres following intratracheal injection were sufficient to enable an examination of the relationship of biopersistence with other biological and toxicological responses. Biopersistence was influenced by both fibre dimensions and solubility.

Air Pollutants, Occupational↗