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Biomedical subjects

R M Douglas

Publications and source records attributed to R M Douglas.

At least 73 records · Page 4Linked to original sources

Physical performance decrements in children with sickle cell anemia.

Prior studies have suggested that cardiorespiratory dysfunction might contribute to the inability of children with sickle cell anemia to exercise competitively with normal children. This article presents a study designed to detect differences in performance of routine physical activities between groups of children having homozygous hemoglobin of sickle cell anemia (HbSS) and those with normal hemoglobin (HbAA). Thirty 10-year-old girls were divided into two equal groups exhibiting no significant differences in height, weight, or body surface area. Each subject performed 20-yd swimming, 40-yd swimming, and 100-yd "potato" foot-racing activities. Results showed significant performance decrements in HbSS compared with HbAA children. Performance decrements on the 20-yd swimming were found to be significantly greater than in either the 40-yd swimming or the 100-yd "potato" races. Assessment of 20-yd swim time as a fraction of 40-yd swim time showed diminished capacity of HbSS children for "burst activity." It is concluded that distance might play a role in the capacity of HbSS children to compete with HbAA children in racing activities such as those encountered in school-based physical education programs. Parents and educators should consider that short distance racing might exaggerate the inability of children with sickle cell anemia to compete with normal children.

Anemia, Sickle Cell↗

Alterations in visual receptive fields in the superior colliculus induced by amphetamine.

Visual response properties were examined in the superficial layers of the superior colliculus (SC) of anesthetized, paralyzed cats before and after i.v. administration of d-amphetamine. Receptive fields (RFs) of single SC units were plotted using small spots of light presented to the contralateral eye. Within the first hour following d-amphetamine injections, RF size gradually increased, reaching a maximum 86 min post-injection. On average, the area of the RF increased by 5.6 times and RF expansion was observed in all single units examined in the superficial layers. Over the subsequent 4-8 h following the injection, RF area gradually decreased and returned to control dimensions. Most RFs displayed asymmetrical patterns of expansion, showing relatively more horizontal than vertical growth. As RF expansion developed, responses to stimuli flashed "on" and "off" at various locations both inside and outside the borders of the control RF became progressively more vigorous. In contrast, no significant changes were noted in direction-selective responses at any time after d-amphetamine injections. Using an array of light bar stimuli of different lengths, the strength of surround suppression was found to be significantly diminished by d-amphetamine. The reduction in surround suppression was especially clear for bar lengths which exceeded the diameter of the control RF. No RF expansion was observed in the superficial layers of the SC when d-amphetamine was injected intravitreally. Furthermore, d-amphetamine had no discernable effect on the RF sizes of cells in the visual cortex. These results suggest that the RF changes in the SC were not of either retinal or cortical origin. We conclude that the mean retinal area which can potentially influence the activity of RFs in the superficial layers of the SC may be on average over 5 times greater than the RF area determined using conventional methods and criteria. These findings raise the interesting possibility that the relatively small size and sharp borders characteristic of RFs in the superficial layers arise from local inhibitory networks which delimit a broader field of excitatory activity supplied by retinal and cortical afferent terminals. Thus, in order to generate the RF changes observed here, either these local inhibitory circuits are amphetamine sensitive, or more likely, these inhibitory networks are dynamically modulated by an, as yet unidentified, amphetamine-sensitive input affecting visual RFs in the superficial layers.

Animals↗

Activation of potassium channels during metabolite detoxification in Escherichia coli.

In bacteria the detoxification of compounds as diverse as methylglyoxal and chlorodinitrobenzene proceeds through the formation of a glutathione adduct. In the Gram-negative bacteria, e.g. Escherichia coli, such glutathione adducts activate one, or both, of a pair of potassium efflux systems KefB and KefC. These systems share many of the properties of cation-translocating channels in eukaryotes. The activity of these systems has been found to be present in a range of Gram-negative bacteria, but not in the glutathione-deficient species of Gram-positive organisms. The conservation of the activity of these systems in a diverse range of organisms suggested a physiological role for these systems. Here we demonstrate that in E. coli cells activation of the KefB efflux system is essential for the survival of exposure to methylglyoxal. Methylglyoxal can be added to the growth medium or its synthesis can be stimulated in the cytoplasm. Under both sets of conditions survival is aided by the activity of KefB. Inhibition of KefB activity by the addition of 10 mM potassium to the growth medium stimulates methylglyoxal-induced cell death. This establishes an essential physiological function for the KefB system.

Antiporters↗

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↗