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Biomedical subjects

R M Douglas

Publications and source records attributed to R M Douglas.

At least 91 records · Page 5Linked to original sources

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↗

Relationship between milk intake and mucus production in adult volunteers challenged with rhinovirus-2.

In the first of three studies investigating the widely held belief that "milk produces mucus," 60 volunteers were challenged with rhinovirus-2, and daily respiratory symptoms and milk and dairy product intake records were kept over a 10-day period. Nasal secretion weights were obtained by weighing tissues collected and sealed immediately after use. Information was obtained on 51 subjects, yielding 510 person-days of observation. Subjects consumed zero to 11 glasses of milk per day (mean, 2.7; SE, 0.08), and secretion weights ranged from zero to 30.4 g/day (mean, 1.1; SE, 0.1). In response to an initial questionnaire, 27.5% reported the practice of reducing intake of milk or dairy products with a cold or named milk or dairy products as bad for colds. Of the latter group, 80% stated the reason as "producing more mucus/phlegm." Milk and dairy product intake was not associated with an increase in upper or lower respiratory tract symptoms of congestion or nasal secretion weight. A trend was observed for cough, when present, to be loose with increasing milk and dairy product intake; however, this effect was not statistically significant at the 5% level. Those who believe "milk makes mucus" or reduce milk intake with colds reported significantly more cough and congestion symptoms, but they did not produce higher levels of nasal secretions. We conclude that no statistically significant overall association can be detected between milk and dairy product intake and symptoms of mucus production in healthy adults, either asymptomatic or symptomatic, with rhinovirus infection.

Adolescent↗

The future role of the National Centre for Epidemiology and Population Health.

Public Health is undergoing a renaissance in Australia, driven by a series of funding imperatives, changing epidemiology, a changing global view of the nature of health and the purpose of health services, and changes in orientation by the politicians. For administrators, the new focus on population health means a change from institutional to community structures and a new set of challenges. The new National Centre for Epidemiology and Population Health at The Australian National University is being developed in this context. Its task is to undertake relevant research in line with the newly adopted Health Targets and to train future leaders in public health. It must draw both on the biological and social sciences in this endeavour.

Australia↗

Dissatisfaction in general practice: what do patients really want?

In 31 general practices in Adelaide, approximately 100 consecutive adult patients aged 15-64 years completed a 21-item questionnaire that related to their dissatisfaction with aspects of the care that was provided in the practice. Fourteen of the practices were "solo" practices, five practices were two-person partnerships and 12 practices involved three or more partners. The 21 items divided naturally into five groups: "architecture", "receptionists", "accessibility", "quality" and "communication". Factor analysis of the responses provided support for the idea that "receptionists", "accessibility" and "communication" were independent issues for the respondents and that "quality" was less discrete and was embedded in a factor which we have labelled "mechanics". For nearly all items, the mean dissatisfaction values for the practices were greatest in the larger practices and least in the two-person practices, with solo practices occupying an intermediate position. The main dissatisfaction related to accessibility and communication. These issues are explored in the light of current trends in the organization of primary medical care.

Adolescent↗

High-frequency discharge of dentate granule cells, but not long-term potentiation, induces c-fos protein.

Competence genes, such as c-fos, may play key roles in information storage in the nervous system by linking relatively brief extracellular signals to long-term changes in the neuron. In support of this idea we, and others, have shown that the c-fos protein occurs in adult mammalian neurons and that higher levels of the protein are induced in certain brain regions after kindled or metrazol-induced seizures in mice and rats, sensory stimulation and mechanical damage in spinal cord neurons, and after depolarization in PC12 cells. Here we report that a massive induction of c-fos protein is observed in dentate granule cells in four conditions that result in repetitive firing: localized seizure discharges; high frequency antidromic activation; orthodromic activation in the presence of iontophoresed bicuculline; and frequency potentiation. However, stimulation of the perforant path with high frequency trains that produced long-term potentiation at the perforant path-granule cell synapse did not reliably induce c-fos in the dentate gyrus. These findings suggest that c-fos induction can follow repetitive neuronal discharge but is not involved in long-term potentiation.

Action Potentials↗

Vitamin A status of children with a history of respiratory syncytial virus infection in infancy.

In order to extend our earlier observation that children who experience frequent respiratory episodes may benefit from Vitamin A supplementation, 206 children aged 2-7 years who had been hospitalized for bronchiolitis during infancy were randomized into a controlled trial of Vitamin A supplementation. Of these, 149 met the criteria of protocol compliance after 12 months of follow-up. Mean plasma retinol at baseline was 39.2 micrograms/100 ml (s.e.m. = 1.0) and did not increase after 12 months (mean = 36.0 micrograms/100 ml, s.e.m. = 0.7) despite the older age of the cohort. The range observed (11.7-73.9 micrograms/100 ml) included some children at risk of marginal Vitamin A deficiency. Mean plasma retinol levels were 20% lower than those of children experiencing frequent respiratory episodes recorded earlier. Oral supplementation did not change plasma retinol levels, nor did it affect respiratory morbidity.

Asthma↗

Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract infections in Australian adults.

Effervescent lozenges containing 10 mg of zinc acetate were evaluated as a treatment of upper respiratory tract infections in a double-blind randomized trial by using a placebo which was indistinguishable to most observers in taste and appearance from the active material. Of the 70 treatment courses used by 55 individuals in 34 families, 63 (33 zinc and 30 placebo) were considered evaluable, in that the volunteer used the medication at least four times daily for at least 3 days, the average utilization being 5.4 days at an average dose of six lozenges daily. Six users of zinc reported nausea (versus no placebo users), and eight reported an unpleasant taste or aftertaste (versus one placebo user). No benefit was observed among the users of zinc acetate. The mean duration of symptoms in users of the zinc was 12.1 days, compared with 7.7 days in those who used the placebo. Nor was any beneficial effect of zinc evident among the four zinc-treated versus the two placebo-treated individuals from whom rhinovirus was grown.

Acetates↗

Prophylactic efficacy of intranasal alpha 2-interferon against rhinovirus infections in the family setting.

In a double-blind evaluation of alpha 2-interferon as prophylaxis against naturally acquired respiratory infections, 120 adult members of 46 Australian families used 325 courses of intranasal spray during a six-month period, applying 5 million IU to the anterior nasal mucosa daily for seven days when respiratory symptoms developed in another member of the family. Used in this way, the alpha 2-interferon was well tolerated, and the rate of minor nasal bleeding (12 percent) did not increase with repeated courses. By comparison with the control group of 109 members of 49 families who used 319 seven-day courses of placebo spray, the users of alpha 2-interferon experienced 33 percent fewer days with nasal symptoms and 41 percent fewer episodes of "definite" respiratory illness. The users of alpha 2-interferon who were exposed to rhinovirus infections experienced 76 percent fewer days with symptoms and 86 percent fewer "definite" illnesses than their counterparts who used placebo. All of the observed clinical benefits, which suggested prevention of 6.8 "definite" respiratory illnesses per 100 courses of medication used, could be explained by a protective effect against illness associated with rhinoviruses that was not demonstrated for influenza A or B or coronavirus 229E.

Administration, Intranasal↗

Pneumococcal carriage and type-specific antibody. Failure of a 14-valent vaccine to reduce carriage in healthy children.

No consistent effect on nasal carriage rates of Streptococcus pneumoniae belonging to vaccine types was observed during a randomized, controlled trial of a 14-valent pneumococcal vaccine, which included 1273 Australian children aged 6 to 54 months. Nasal carriage of S pneumoniae was associated with a significantly elevated homotypic serum antibody concentration for types 18C, 19F, and 23F, but not for types 6A and 14 (these five types are the most important causes of pneumococcal infections in children). Upper respiratory tract carriage seems to play an important role in natural acquisition of antibody to some but not all pneumococcal serotypes. These findings help to explain why pneumococcal vaccine fails to protect young children from acute otitis media.

Antibodies, Bacterial↗

A self-contained method of evaluating patient dissatisfaction in general practice.

A method is described which enables patient dissatisfaction to be measured in a consecutive sample of adults attending for consultation in general practice. The method has been found to be practicable and acceptable, both to patients and doctors and to yield results which are both consistent and useful to the doctor in structuring his practice.

Adolescent↗

A self-contained method of evaluating the provision of preventive care in general practice.

In an earlier paper a method was described by which general practitioners are able to obtain dissatisfaction data from their patients by means of questionnaires. A similar approach has been used to study preventive care activities of general practitioners. We have found it to be practicable and acceptable to patients and surgery personnel. It also yields results which are consistent and which have apparently stimulated some practitioners to alter their practice behaviour by increasing their preventive care activities.

Adolescent↗