PubMed Health⌕ Search

Biomedical subjects

M D Robertson

Publications and source records attributed to M D Robertson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Postmortem drug metabolism by bacteria.

Studies were undertaken to determine the possible role of enteric bacteria in the postmortem bioconversion of the nitrobenzodiazepines flunitrazepam, clonazepam, and nitrazepam. Flunitrazepam, clonazepam, and nitrazepam were completely metabolized in blood in the presence of eight species of enteric bacteria to their respective 7-amino-metabolites. The rates of metabolism, at 37 degrees C, ranged from 0.1 ng/mL/min for Streptococcus faecalis to 8.8 ng/mL/min for Clostridium perfringens. The rate of conversion was reduced to 87% by a combination of 0.7% (w/v) sodium fluoride and potassium oxalate, and almost completely inhibited (96%) by 1% (w/v) sodium fluoride. pH had variable effects on the rate of metabolic bioconversion of nitrobenzodiazepines, while increasing temperatures were found to generally increase the rate of nitrobenzodiazepine bioconversion. These data support the proposal that bacteria may mediate postmortem bioconversion of the nitrobenzodiazepines.

Adult↗
PubMed1994

Responsibility analysis: a methodology to study the effects of drugs in driving.

In order to study the role of drugs in driving, a responsibility analysis was developed to allow an assessment to be made of the driver's culpability or responsibility in an accident. Factors possibly mitigating drivers' responsibility in each accident were identified and scored. Factors considered were: condition of road, condition of vehicle, driving conditions, accident type, witness observations, road law obedience, difficulty of task, and level of fatigue. If a sufficient number of mitigating factors were identified a driver would be found to be either partly or totally exonerated from blameworthiness and scored either as a contributory or nonculpable driver. If drugs present in a driver contributed to accident causation, it would be expected that they would be overrepresented in culpable drivers, i.e. those drivers not exonerated from blame. A total of 341 driver fatalities occurring in Victoria were analysed for blood alcohol content (BAC). Twenty-nine percent had a BAC over .05% (the legal limit in Victoria). Alcohol-positive drivers were statistically overrepresented in the culpable group (p < .001), in single-vehicle accidents (p < .05) and those accidents in which vehicles left the road for no apparent reason (p < .001). Odds-ratio estimation of relative risk of culpable and nonculpable drivers showed that the relative risk rose disproportionately to BAC.

Accidents, Traffic↗
PubMed1990

Impaired chemotactic responses of bronchoalveolar leukocytes in experimental pneumoconiosis.

Rats were exposed to clouds of the following pneumoconiotic dusts: quartz, coal-mine dust, and chrysotile asbestos at 10 or 50 mg/m3 for 8, 32, and 75 days; for comparison, rats were also exposed to the non-pathogenic dust titanium dioxide (TiO2). The bronchoalveolar leukocytes (macrophages and neutrophils) from dust-exposed and control rats were obtained by lavage and tested for their ability to migrate toward zymosan-activated serum. Varying amounts of neutrophils were present depending on the ability of the dust to cause inflammation and the length of exposure. There was a marked loss of chemotactic ability in leukocytes from rats inhaling the pneumoconiotic dusts compared with controls; TiO2-exposed leukocytes had some impairment of chemotaxis, but this was substantially less than that found with the pneumoconiotic dusts. The loss of chemotactic activity did not correlate with the percentage of neutrophils in the lavage cells except when there were very high levels of neutrophils, and there was substantial impairment of chemotaxis with negligible numbers of neutrophils, showing that macrophage chemotaxis was impaired. A phagocytic burden within the leucocytes was not sufficient alone to inhibit chemotaxis, nor was the loss of chemotactic activity due to occupied receptors, since incubation failed to restore chemotaxis. Loss to chemotactic activity by leukocytes from pneumoconiotic dust-exposed lung could be an important factor in the development of pneumoconiosis.

Animals↗
PubMed1990

Contrasting bronchoalveolar leukocyte responses in rats inhaling coal mine dust, quartz, or titanium dioxide: effects of coal rank, airborne mass concentration, and cessation of exposure.

The aim of this study was to determine the bronchoalveolar leukocyte response to airborne coal mine dust; quartz and titanium dioxide were used as positive and negative controls, respectively. Groups of rats were exposed to airborne mass concentrations of 10 and 50 mg/m3 of the dusts for 7 hr/day, 5 days/week and their bronchoalveolar space was lavaged at time points between 2 and 75 days of exposure, to assess the leukocyte response. This study revealed time-dependent and airborne mass concentration-dependent recruitment of neutrophils and macrophages into the bronchoalveolar region with coal mine dust inhalation but no real difference in the magnitude of the response between coal mine dusts from collieries mining coal of different rank and quartz content although the maximum quartz content in the dusts used was 6%. The inflammatory response was much less than that produced by quartz, at similar airborne mass concentrations, and more than that produced by titanium dioxide which was, in general, a poor inflammogen in the rat lung. Groups of rats were exposed to the airborne dusts for 32 or 75 days, then removed from the exposure chambers, and allowed to recover by breathing room air for a further 64 days. During this recovery period there was marked progression of the leukocyte response with quartz and persistence of the response with coal mine dust. Chronic recruitment of leukocytes to the lungs of individuals inhaling coal mine dust is likely to be an important factor in the development of coal workers' pneumoconiosis.

Administration, Inhalation↗
PubMed1989

Killing of Aspergillus fumigatus spores by human lung macrophages: a paradoxical effect of heat-labile serum components.

Spores of Aspergillus fumigatus can interfere with certain aspects of phagocytic cell function. In this study we have looked at the ability of human pulmonary macrophages to bind and kill spores of A. fumigatus which have been opsonized in untreated and heat-treated serum. For comparison, the non-pathogenic fungus Penicillium ochrochloron has been used. More than 60% of spores of both fungal species became cell-associated with the macrophages following incubation at 37 degrees C for 1 h. Spores of A. fumigatus opsonized in 5% pooled normal serum were significantly more resistant to killing by pulmonary macrophages than similarly opsonized spores of P. ochrochloron (p less than 0.02). However, serum which had been heated to 56 degrees C for 30 min prior to opsonization significantly increased (by approximately 80%) the ability of pulmonary macrophages to kill spores of A. fumigatus when compared with untreated sera (p less than 0.001). No such difference occurred with spores of P. ochrochloron. These unexpected observations fit with the known propensity of A. fumigatus to colonize the airways of patients with asthma and cystic fibrosis, conditions in which a protein-rich bronchial exudate characteristically occurs. Moreover, the presence of such a protective mechanism in a soil organism strongly suggests that complement-like substances may also play a role in protozoal phagocytosis. This is an area of research that does not appear to have been investigated.

Aspergillus fumigatus↗
PubMed1988

Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide.

The kinetics of the bronchoalveolar response was assessed in rats exposed, at equal airborne mass concentration (10 mg/m3), to titanium dioxide--a non-pathogenic dust--and the two pathogenic mineral dusts quartz and chrysotile asbestos. Rats were killed at intervals over a 75 day exposure period and groups of rats exposed for 32 and 75 days after recovery for two months. Bronchoalveolar lavage was carried out and the lavage fluid characterised for cellular content, macrophage activation, and concentrations of free total protein, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase. Inhalation exposure to the two pathogenic dusts resulted in an increased number of leucocytes, macrophage activation, and increased levels of free enzymes and total protein. The pattern and magnitude of the responses to quartz and chrysotile differed. Chrysotile caused less inflammation than quartz, and the main cellular response peaked around the middle of the period of dust exposure whereas the highest levels of enzymes occurred towards the end. The difference in timing suggests that macrophages were not available for lavage towards the end of the exposure, owing to their playing a part possibly in deposition of granulation tissue. Quartz caused a greater cellular and enzyme response than chrysotile, particularly towards the end of the dust exposure phase. There was a noticeable progression of inflammation in the quartz exposed groups left to recover for two months, but not in the chrysotile recovery groups.

Animals↗
PubMed1987

Inhibition of phagocyte migration and spreading by spore diffusates of Aspergillus fumigatus.

Previous studies have shown that spores of Aspergillus fumigatus inhibit phagocytosis and killing by macrophages and polymorphonuclear leucocytes. In order to identify the mechanisms of this interference with host defences, we have examined the effects of A. fumigatus spore diffusates on phagocytic cell function. For comparison, we have used spore diffusates of the non-pathogenic fungus Penicillium ochrochloron. The diffusates of A. fumigatus reduced the number of human polymorphonuclear leukocytes migrating towards a known chemoattractant by approximately 50% (p less than 0.001). In addition spore diffusates of A. fumigatus significantly decreased (p less than 0.001) the capacity of primed mouse peritoneal exudate cells to spread on glass. Spore diffusates of P. ochrochloron showed no comparable inhibitory effects. These studies have shown that spore diffusates of A. fumigatus inhibit the movement of the phagocytic cell membrane and are thus able to interfere with a primary function of phagocytic cells.

Animals↗
PubMed1987

Suppression of host defences by Aspergillus fumigatus.

An important feature of the microbicidal action of phagocytic cells is their ability to produce reactive oxygen intermediates. In an attempt to identify the mechanisms by which the fungus Aspergillus fumigatus resists normal host defences the effect of spores and spore diffusates of A fumigatus on the production of superoxide anion and hydrogen peroxide by primed rodent phagocytic cells has been measured. For comparison we have used the non-pathogenic fungus Penicillium ochrochloron. Production of these reactive oxygen intermediates in response to A fumigatus was significantly lower than that in response to P ochrochloron. A similar reduction was achieved by diffusate prepared from freshly washed spores. The inhibitory component was of low molecular weight (less than 14,000) and its effect was dose dependent. These results suggest that spores of A fumigatus fail to trigger and also inhibit the production of reactive oxygen intermediates by phagocytic cells.

Animals↗
PubMed1987

Resistance of spores of Aspergillus fumigatus to ingestion by phagocytic cells.

Phagocytic cells are believed to have an important role in the eradication of fungal spores from the lung. The ability of human and mouse cells to phagocytose the opportunistic fungus Aspergillus fumigatus has been examined, spores of the non-pathogenic fungus Penicillium ochrochloron being used for comparison. Most spores became associated with cells. Those of A fumigatus appeared to remain bound to the surface of the phagocyte rather than being ingested; in contrast, P ochrochloron spores appeared to be phagocytosed more readily, although they also were seen, in small numbers, o n the cell surface. In view of the subjective nature of these observations, the effects of spore diffusates on phagocytosis were examined. Diffusates from spores of A fumigatus were shown to inhibit phagocytosis of antibody coated radiolabelled sheep red blood cells by primed mouse phagocytic cells. Diffusates of spores of P ochrochloron had no such effect. These results suggest that when spores of A fumigatus become bound to the surface of phagocytes they are able to release a substance that inhibits their ingestion while having little or no effect on surface binding.

Animals↗
PubMed1984

Serum immunoglobulin levels and humoral immune competence in coalworkers.

Serum immunoglobulin (Ig) levels were measured in 788 coalworkers and 121 nonmining controls for comparison with the radiological category of pneumoconiosis after taking into account age and smoking habit. In addition a simple assessment of humoral immune competence was made by estimating the titre of serum antibody against the common gut commensal Escherichia coli. Smoking was found to depress serum IgA and IgM whilst levels of IgG and IgA increased slightly with age. Men with radiological signs of coalworkers pneumoconiosis (CWP) had significantly raised levels of IgA and IgG with increasing pneumoconiosis category. Even coalworkers with less than category 1 simple pneumoconiosis had raised levels of IgA, suggesting that increased production of this immunoglobulin occurs before radiologically identifiable pathological changes have occurred in the lung tissue. No association between reduced humoral immune competence and radiological category of pneumoconiosis was found. Whether high Ig levels in men exposed to coal dust are merely a passive response to dusted lung tissue or whether they indicate that an immunological process is important in the development of pneumoconiotic lesions remains uncertain.

Age Factors↗
PubMed1984

Prevalence of reoviruses in commercial chickens.

The prevalence of reoviruses in commercial chickens with the runting/stunting syndrome, tenosynovitis, and normal chickens was investigated. Reoviruses were isolated from 3-week-old chickens affected with the runting/stunting syndrome and from older chickens with tenosynovitis; viruses were isolated from tissues with and without lesions. Reoviruses were also frequently isolated from rectal contents of normal 3-week-old chickens, and there was serological evidence of previous reovirus infection in all flocks of adult meat breeder chickens examined. The widespread occurrence of reoviruses in both normal and diseased chickens indicates that the isolation of reoviruses from tissues of chickens with lesions does not necessarily imply any aetiological relationship of reovirus with disease, even in the absence of other known causes. However, the occurrence of reovirus in normal chickens does not preclude an aetiological relationship with disease and further investigation of strain variation and possible virulence factors in avian reoviruses is required.

Animals↗
PubMed1983

Some immunological studies on coalworkers with and without pneumoconiosis.

This work formed part of a series of studies devised to investigate immunological markers which it was considered might reflect individual susceptibility to the development of coalworkers' pneumoconiosis and especially progressive massive fibrosis. Estimations of T and B lymphocytes and white blood cell counts (WBCC) were performed on blood samples from 324 coalworkers grouped according to radiographic category of pneumoconiosis, age, and smoking habits. A subgroup of 43 men was further screened for both humoral anti-lung antibodies (ALA) and direct lymphocyte-mediated cellular cytotoxicity (LMCC) towards human embryonic lung fibroblasts (HEL). In addition 673 serum samples obtained during a previous study of autoimmune factors in coalworkers were screened for humoral antibodies to HEL cells. The only correlation found between category of pneumoconiosis and alterations in WBCC, percentage or absolute numbers of lymphocytes, or the presence of anti-lung antibodies was a decrease in a subgroup of T lymphocytes with increasing severity of pneumoconiosis. The major factor influencing these parameters in this study was the smoking status of the man. Smokers showed increased WBCC and lymphocyte numbers and a higher frequency of ALA and LMCC when compared with nonsmokers.

Adult↗
PubMed1982

Autoantibodies in coalminers: their relationship to the development of progressive massive fibrosis.

Sera from 2421 coalminers, representing all the radiological categories of pneumoconiosis, and from 260 healthy blood donors, as controls, were examined for antinuclear factor and rheumatoid factor. Antinuclear factors were present in 21.5% of sera from the controls and in 23.1% from the coalminers' group. Rheumatoid factor was present in 5.3% of coalminers and as expected occurred particularly in the few men with progressive massive fibrosis who also had rheumatoid disease. The combined prevalence of both factors showed an increase with age at all disease levels and a significant association with pneumoconiosis category only in men older than 60 years. This study provides no evidence that autoantibodies are likely to be of value in detecting men predisposed to the development of massive fibrosis other than those with rheumatoid disease.

Antibodies, Antinuclear↗