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Biomedical subjects

R M Douglas

Publications and source records attributed to R M Douglas.

At least 19 recordsLinked to original sources

Indoor nitrogen dioxide and childhood respiratory illness.

Nitrogen dioxide is produced from the combustion of fossil fuels and as an emission from gas-fired appliances, and is also a component of tobacco smoke. Nitrogen dioxide has been shown in experimental animals to be toxic to the respiratory tract. A n number of recent studies have suggested that children exposed to significant levels of nitrogen dioxide in the home may be more susceptible to respiratory illness than children exposed to normal ambient levels. Respiratory illness is a major cause of morbidity in children everywhere. Here, we review the available evidence of this association and explore methodological issues in measurement of nitrogen dioxide exposure--misclassification of subjects, symptom bias and confounding. It has recently been shown that some New South Wales school rooms, where unflued gas heaters are often used as a source of warmth, have nitrogen dioxide levels which are above recommended ambient levels for outside air. This has underlined the need for setting standards for indoor levels of various pollutants, and cohort studies are suggested, to include personal monitoring and prospective data collection techniques.

Air Pollution, Indoor

Acute respiratory illness in Adelaide children--the influence of child care.

OBJECTIVE: To test the hypothesis that children attending child care centres are more likely to be prone to acute respiratory illness. DESIGN: A case-control study. SETTING: A community-based study in the Adelaide metropolitan area. PARTICIPANTS: A randomly selected sample of Adelaide children whose births were registered in 1983. MAIN OUTCOME MEASURE: A respiratory illness score was calculated for each child, based on parents' reports of acute respiratory illness in the previous 12 months. RESULTS: Information was obtained by postal survey for 2618 children (mean age at time of study, 26 months). Eight hundred and nineteen of these children (31%) were reported to be regular or occasional attenders of child care centres or crèches. Home interviews were carried out with parents of children whose respiratory illness scores fell in the top 20% of the range and those whose score was in the bottom 20%. Children prone to respiratory illness were more likely to be users of child care centres or crèches than the children who were not prone (odds ratio = 2.28; 95% confidence interval, 1.53-3.40). The risk of being prone to respiratory illness increased with the frequency of use of child care, and tended to be greater the younger children were when they first attended child care centres. Adjustment in multivariate analysis for confounding factors made little difference to the strength of the association of proneness to respiratory illness with the use of child care (adjusted odds ratio = 2.23; 95% confidence interval 1.38-3.61). CONCLUSION: Use of child care centres is an important cause of acute respiratory illness among Australian children.

Case-Control Studies

HIV prevalence and risk behaviours for HIV transmission in South Australian prisons.

During the latter half of 1989, HIV prevalence in South Australian prisoners was 1.4%. The prevalence of HIV infection across the prison system did not change significantly during 1989 but there was clustering of HIV-infected prisoners in some prisons. Almost half the prisoners from all of the South Australian prisons agreed to participate in our studies, from which we estimate that about 42% of prisoners engage in risk behaviours at least once while incarcerated. Prisoners estimated that 36% of all prisoners inject drugs intravenously at some stage during their stay and that 12% engage in anal intercourse at least once. Interviews with former prisoners who had a history of intravenous drug use revealed that about half had injected themselves while in prison, 60% shared needles and most did not clean shared needles adequately. Most of these prisoners injected themselves once a month or less frequently. The conditions for spread of HIV within the prison system exist but at the current prevalence of infection, transmission can be expected to be infrequent. The opportunity exists now to improve and expand preventive measures.

Adult

The distribution of homologues of the Escherichia coli KefC K(+)-efflux system in other bacterial species.

Using a variety of techniques the distribution of the glutathione-regulated KefC K(+)-transport system among bacterial species was investigated. The presence of similar systems in a number of Gram-negative bacteria was demonstrated. In contrast, the system appeared to be absent from most Gram-positive bacteria tested with the exception of Staphylococcus aureus. Using the cloned Escherichia coli kefC gene as a probe for Southern hybridization it was shown that only limited DNA sequence homology exists with other bacteria, even when closely related members of the enteric group were examined.

Bacterial Proteins

The cloning and DNA sequence of the gene for the glutathione-regulated potassium-efflux system KefC of Escherichia coli.

The kefC gene of Escherichia coli encodes a potassium-efflux system that is regulated by glutathione metabolites. The close proximity of the E. coli kefC gene to the folA gene, encoding dihydrofolate reductase, has been utilized to clone the structural gene for the system from a Clarke-Carbon plasmid. The cloned gene has been refined to a region of DNA approximately 2.1 kb in length using exonuclease III-generated deletions and random MudII1734 (lacZ) insertions. The direction of transcription has been deduced from the orientation of the Mu insertions in the cloned DNA. A hybrid protein consisting of approximately two thirds of the KefC protein fused to beta-galactosidase has been shown to be membrane-located. The DNA sequence of the gene has been determined and an open reading frame of 1.86 kb has been located which could encode a protein of 620 amino acids (79010 Da). Using the T7 expression system a membrane protein, of apparent molecular mass 55-60 kDa, has been shown to be encoded by the kefC gene. The predicted protein sequence shows a highly hydrophobic amino-terminus and a strongly hydrophilic carboxy-terminus. Comparison of the amino acid sequence of the kefC gene product with those of two glutathione-utilizing enzymes, glyoxalase and dehalogenase, has revealed some similarities.

Amino Acid Sequence

Corneal ulceration due to Nocardia asteroides.

A case of corneal ulceration due to infection with Nocardia asteroides is described. Microbiological examination of corneal scrapings permitted accurate diagnosis and suggested appropriate therapy. Nineteen other cases that have been described in the world literature are reviewed.

Adult

Position-specific adaptation in simple cell receptive fields of the cat striate cortex.

1. Responses of simple cells in cat striate cortex were studied with flashed light-slit stimuli. The responses to bars flashed in different positions in the receptive field were assessed quantitatively before and after periods of prolonged stimulation of one small region. This type of prolonged stimulation resulted in reduced responsivity over a limited zone within the simple cell receptive field. 2. The adaptation-induced responsivity decrement was generally confined to the receptive-field subregion that was adapted (either ON or OFF). Prolonged stimulation within an ON region did not usually result in adaptation effects that spread into neighboring OFF regions. Furthermore, the adaptation-induced response decrement did not necessarily spread throughout the subregion in which the adapting stimulus was presented. The adaptation effects from prolonged stimulation at a single receptive-field position spread throughout the subregion in nearly one-half of the 25 cells examined for position-specific adaptation. Another subpopulation of neurons (n = 12) displayed adaptation effects that spread through only one-half of the subregion, whereas in two neurons the spread of the adaptation effect was even more restricted and encompassed only one-fourth of the subregion. 3. The spread of adaptation was not systematically related to the size of the stimulus presented, the size of the receptive field, or the magnitude of the adaptation-induced response decrements but was significantly correlated with the spatial wavelength of the cell (the reciprocal of the cell's preferred spatial frequency) and with the size of the subregion in which the adapting stimulus was presented. Cells with large receptive-field subregions and long wave-lengths showed adaptation effects that spread further than those of cells with small subregions. 4. The adaptation effects from repeated stimulation at a single receptive-field position did not spread symmetrically across the receptive field, and the preferred direction of motion for a given cell indicated the direction of the asymmetric spread of the adaptation. Receptive-field positions that would be stimulated by a light slit originating at the point of adaptation and moving in the preferred direction (preferred side) showed greater adaptation-induced response decrements than did receptive-field positions that would be stimulated by a light slit moving in the opposite direction from the point of adaptation (nonpreferred side). There was significant enhancement of responses at some receptive-field positions on the nonpreferred side of the point of adaptation.(ABSTRACT TRUNCATED AT 400 WORDS)

Acclimatization

Acute respiratory infections in children in the developing world.

The profound decline in death rates from respiratory infections in recent decades in the developed countries of the world is a complex phenomenon that probably results from a combination of socioeconomic and environmental change and modern medical care. Death rates from respiratory infections in the developing world are very variable, and there is evidence that they can decrease dramatically when effective health services are engrafted onto a social environment in which mothers are literate and trained to observe their children's health. A worldwide case management program aimed at making lifesaving antibiotics and oxygen available for treatment of children in deprived areas is currently being spearheaded by the World Health Organization and rests on simplified approaches to diagnosis that are widely disseminated to parents and primary health workers. These guidelines have been shown in field studies to contribute to changes in child mortality. The epidemiology of pneumonia in childhood seems similar worldwide. Most children suffer five to eight respiratory infections annually if they live in the cities and fewer if they live in rural areas but, in deprived circumstances, pneumonia complicates the infection much more often and the principal organisms are pneumococcus and Haemophilus influenzae. A vaccine approach to these two organisms is attractive and needs further field testing. Meanwhile, a case management approach, making antibiotics available on a rational basis worldwide, is capable of saving lives. Until mothers in the developing world have confidence in the survival of their children, they are unlikely to be attracted to control of their fertility.

Bacterial Vaccines

Could preventive intranasal interferon lower the morbidity in children prone to respiratory illness?

Recent studies have demonstrated that rhinovirus infections can be prevented in the family setting through use of intranasal interferon sprays which are commenced when another family member develops a cold. One hundred and twenty-seven children aged 4-9 years who had been hospitalized during their first year of life for severe infections caused by respiratory syncytial virus were studied virologically and epidemiologically during a seven-month period which included the winter months. The hypothesis was that a significant part of their respiratory morbidity would be preventable by a contact prophylaxis approach using intranasal interferon. However, the findings suggest that a preventive approach of this kind would not substantially reduce the burden of respiratory illness in these children because: the target children themselves more often introduced illness into the family than did other household members; rhinovirus infections preventable by interferon were associated with little lower respiratory morbidity; and rhinoviruses were minor contributors to the total respiratory illness burden in these respiratory illness-prone children.

Administration, Intranasal

Acute respiratory illness in Adelaide children. II: The relationship of maternal stress, social supports and family functioning.

In a community-based study we investigated the relationships between maternal stress, maternal social supports, family functioning and proneness to acute respiratory illness (AR1) in childhood. 'Prone' and 'not prone' children were identified from the responses to a mail questionnaire sent to the addresses of a randomly selected group of Adelaide children who had been born in 1983. 'Prone' children (n = 255) were defined by a respiratory score (based on frequency and severity of reported symptoms in the preceding 12 months) in the top quintile of the distribution, while 'not prone' children (n = 227) were defined by a score in the bottom 20% of the range. Further information was obtained from a questionnaire administered at a home visit. Maternal stress levels were determined from a combination of major life events, minor life events and psychological distress. Maternal stress was significantly associated with respiratory proneness in a stepwise multiple logistic regression (adjusted odds ratio/high versus low = 3.8; 95% confidence interval 2.0-7.2; p = 0.000), while controlling for the effects of maternal smoking, group child care, early chest illness, number of siblings, breastfeeding, occupation, sex, age, home heating, birthweight and parental history of respiratory illness. Family dysfunction was associated with respiratory proneness in bivariate analyses but not after adjustment for the effects of other psychosocial factors in multivariate analyses. Lack of maternal social support was not associated with having a child who was prone to respiratory illness. These findings raise a number of questions about the nature and direction of the relationship between parental psychological status and child health.

Acute Disease

Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers.

A double-blind, placebo-controlled trial was conducted to study the effects of over-the-counter analgesic/antipyretic medications on virus shedding, immune response, and clinical status in the common cold. Sixty healthy volunteers were challenged intranasally with rhinovirus type 2 and randomized to one of four treatment arms: aspirin, acetaminophen, ibuprofen, or placebo. Fifty-six volunteers were successfully infected and shed virus on at least 4 days after challenge. Virus shedding, antibody levels, clinical symptoms and signs, and blood leukocyte levels were carefully monitored. Use of aspirin and acetaminophen was associated with suppression of serum neutralizing antibody response (P less than .05 vs. placebo) and increased nasal symptoms and signs (P less than .05 vs. placebo). A concomitant rise in circulating monocytes suggested that the suppression of antibody response may be mediated through drug effects on monocytes and/or mononuclear phagocytes. There were no significant differences in viral shedding among the four groups, but a trend toward longer duration of virus shedding was observed in the aspirin and acetaminophen groups.

Acetaminophen

Activation of potassium efflux from Escherichia coli by glutathione metabolites.

The mechanism by which N-ethylmaleimide (NEM) elicits potassium efflux from Escherichia coli has been investigated. The critical factor is the formation of specific glutathione metabolites that activate transport systems encoded by the kefB and kefC gene products. Formation of N-ethyl-succinimido-S-glutathione (ESG) leads to the activation of potassium efflux via these transport systems. The addition of dithiothreitol and other reducing agents to cells reverses this process by causing the breakdown of ESG and thus removing the activator of the systems. Chlorodinitrobenzene, p-chloromercuribenzoate and phenylmaleimide provoke similar effects to NEM. lodoacetate, which leads to the formation of S-carboxymethyl-glutathione, does not activate the systems but does prevent the action of NEM. It is concluded that the KefB and KefC systems are gated by glutathione metabolites and that the degree to which they are activated is dependent upon the nature of the substituent on the sulphydryl group.

Biological Transport

Acute respiratory illness in Adelaide children: breast feeding modifies the effect of passive smoking.

STUDY OBJECTIVE: The aim was to investigate the relation between passive smoking and childhood acute respiratory illness. DESIGN: The study involved an initial postal survey on a random sample of children followed by a case-control study based on the survey. A respiratory illness score was calculated from maternal reports of episodes of illness in the previous 12 months. SETTING: The study was a population survey based on Adelaide metropolitan area in South Australia. PARTICIPANTS: The reference population (n = 13,996) was all live born children registered in South Australia in 1983 whose parents lived in Adelaide metropolitan area. Of these, 4985 families were contacted by post and from 2125 respondents, 1218 (58%) gave consent for home interview. "Cases" were children with respiratory illness scores in the top 20%, controlling for age and time of year (n = 258); "controls" were taken in the bottom 20% (n = 231). MEASUREMENTS AND MAIN RESULTS: Maternal smoking in the first year of life was associated with a doubling in relative odds of respiratory proneness in the child (odds ratio = 2.06, 95% CI 1.25-3.39) after adjustment for confounding by parental history of respiratory illness, other smokers in the home, use of group child care, parent's occupation, and levels of maternal stress and social support. There was no evidence that this association was attributable to differences in the way smoking and non-smoking parents perceived or managed childhood acute respiratory illness. Maternal smoking in the first year, without smoking in pregnancy, was also associated with increased risk of respiratory proneness (odds ratio 1.75, 95% CI 1.03-3.0), showing an effect of passive smoking independent of any in utero effect. There was a strong negative effect modification by breast feeding: relative odds of respiratory proneness with maternal smoking were seven times higher among children who were never breast fed than among those who were breast fed. CONCLUSIONS: The results suggest a relatively small but real effect of passive smoking on childhood acute respiratory illness. Effect modification by breast feeding may be due to a combination of behavioural and biological mechanisms.

Acute Disease