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Biomedical subjects

R M Douglas

Publications and source records attributed to R M Douglas.

At least 37 records · Page 2Linked to original sources
PubMed2001

Decreased CSF pH at ventral brain stem induces widespread c-Fos immunoreactivity in rat brain neurons.

Physiological evidence has indicated that central respiratory chemosensitivity may be ascribed to neurons located at the ventral medullary surface (VMS); however, in recent years, multiple sites have been proposed. Because c-Fos immunoreactivity is presumed to identify primary cells as well as second- and third-order cells that are activated by a particular stimulus, we hypothesized that activation of VMS cells using a known adequate respiratory stimulus, H(+), would induce production of c-Fos in cells that participate in the central pH-sensitive respiratory chemoreflex loop. In this study, stimulation of rostral and caudal VMS respiratory chemosensitive sites in chloralose-urethane-anesthetized rats with acidic (pH 7.2) mock cerebrospinal fluid induced c-Fos protein immunoreactivity in widespread brain sites, such as VMS, ventral pontine surface, retrotrapezoid, medial and lateral parabrachial, lateral reticular nuclei, cranial nerves VII and X nuclei, A(1) and C(1) areas, area postrema, locus coeruleus, and paragigantocellular nuclei. At the hypothalamus, the c-Fos reaction product was seen in the dorsomedial, lateral hypothalamic, supraoptic, and periventricular nuclei. These results suggest that 1) multiple c-Fos-positive brain stem and hypothalamic structures may represent part of a neuronal network responsive to cerebrospinal fluid pH changes at the VMS, and 2) VMS pH-sensitive neurons project to widespread regions in the brain stem and hypothalamus that include respiratory and cardiovascular control sites.

Animals↗
PubMed2000

Reduced visual acuity impairs place but not cued learning in the Morris water task.

The Morris water task is a standard method for testing spatial learning in rodents. In a place version of the task, animals utilize multiple visual cues to learn the location of a hidden platform. The ability of animals to locate a cued platform is often used to qualitatively test for possible non-cognitive contributions to deficient place learning, including reduced visual function. We investigated the role of visual acuity in water maze performance quantitatively by depriving rats of pattern vision during a critical period for visual plasticity, which reduced their acuity by approximately 27% and then tested them in typical place and cued platform configurations of the Morris water task. Animals with reduced visual acuity had a significant deficit in place learning, but eventually reached the same escape latency as non-deprived animals. Deprived and non-deprived animals, however, did not differ in their ability to locate a cued platform following place learning. These data indicate that reduced visual acuity in rats can influence measurement of their place learning and that a typical cued platform version of the task cannot detect a modest, but significant, visual deficit.

Animals↗
PubMed2000

Na/HCO3 cotransporters in rat brain: expression in glia, neurons, and choroid plexus.

We studied the expression and distribution of Na/HCO(3) cotransporters in rat brain using polynucleotide probes and polyclonal antibodies derived from the electrogenic rat kidney Na/HCO(3) cotransporter (rkNBC). In whole brain, we observed a single mRNA ( approximately 7.5 kb) by Northern hybridization and a major approximately 130 kDa protein by immunoblotting with a polyclonal antiserum directed against the C terminus of rkNBC. NBC mRNA and protein were present in cortex, brainstem-diencephalon, and cerebellum. In situ hybridization revealed NBC mRNA expression throughout the CNS, with particularly high levels in olfactory bulb, hippocampal dentate gyrus, and cerebellum. NBC mRNA was present in glial cells (e.g., Bergmann glia of cerebellum and hippocampal astrocytes) and neurons (e.g., granule cells of dentate gyrus and neurons of cortex or striatum). Double hybridization of mRNA encoding NBC and glutamate transporter 1 (glial marker) confirmed that both glia and neurons express NBC. Indirect immunofluorescence microscopy demonstrated NBC protein throughout the CNS, particularly in hippocampus and cerebellum. Although NBC mRNA was restricted to cell bodies, NBC protein was distributed diffusely, compatible with a localization in cell processes and perhaps cell bodies. Double labeling with glial fibrillary acidic protein (astrocytic marker), microtubule-associated protein 2 (neuronal marker), or 2',3'-cyclic mononucleotide 3'-phosphodiesterase (oligodendrocytic marker) demonstrated expression of NBC protein in specific subpopulations of both glia and neurons. Moreover, NBC protein was present in both cultured hippocampal astrocytes and cortical neurons. NBC mRNA and protein were also present in epithelial cells of choroid plexus, ependyma, and meninges. Our results are thus consistent with multiple novel roles for Na/HCO(3) cotransport in CNS physiology.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2000

Making a difference to socioeconomic determinants of health in Australia: a research and development strategy.

Disparities in health across the socioeconomic spectrum are now recognised worldwide and demand policy action. Pathways from social disadvantage to health outcomes are poorly understood, and reducing social disadvantage poses crosscutting political, moral and methodological issues. The Health Inequalities Research Collaboration, an initiative of the Commonwealth Department of Health and Aged Care, is establishing a research and development process to support departmental efforts to reduce health inequalities. The collaboration is building research networks in child development, community resources and primary healthcare. Policy action needs to extend beyond the health portfolio and the role of government. Broad strategies are required, as is research to fearlessly evaluate the health effects of government policy, economic activity and cultural change. The Canadian Institute for Advanced Research is a model for national research of the kind needed in Australia.

Australia↗
PubMed2000

Columnar distribution of serotonin-dependent plasticity within kitten striate cortex.

Recent studies have identified the potential for an important role for serotonin (5-HT) receptors in the developmental plasticity of the kitten visual cortex. 5-HT(2C) receptors are transiently expressed in a patchy fashion in the visual cortex of kittens between 30-80 days of age complementary to patches demarcated by cytochrome oxidase staining. 5-HT, operating via 5-HT(2C) receptors, increases cortical synaptic plasticity as assessed both in brain slices and in vivo. Herein, we report that bath application of 5-HT substantially increases the probability of long-term potentiation within 5-HT(2C) receptor-rich zones of cortex, but this effect is not observed in the 5-HT(2C) receptor-poor zones. Instead, in these zones, 5-HT application increases the probability of long-term depression. These location-specific effects of 5-HT may promote the formation of compartment-specific cortical responses.

Acetylcholinesterase↗
PubMed2000

Vitamin C for preventing and treating the common cold.

BACKGROUND: The role of oral ascorbic acid (vitamin C) in the prevention and treatment of colds remains controversial despite many controlled trials. There have also been a number of efforts to synthesize and/or overview the results of these trials, and controversy over what these overviews tell us. OBJECTIVES: The objective of this review was to answer the following two questions: (1) Does regular high dosage supplementation with vitamin C reduce the incidence of colds? (2) Does taking vitamin C in high doses at the onset of a cold have a therapeutic effect? SEARCH STRATEGY: This review currently deals only with published trials from two previously published reviews by Kleijnen 1989 and Hemila 1992. SELECTION CRITERIA: Randomised and non-randomised trials of vitamin C taken to prevent or treat the common cold. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Thirty trials were included. The quality of the included trials was variable. Vitamin C in doses as high as one gram daily for several winter months, had no consistent beneficial effect on incidence of the common cold. For both preventive and therapeutic trials, there was a consistently beneficial but generally modest therapeutic effect on duration of cold symptoms. This effect was variable, ranging from -0.07% to a 39% reduction in symptom days. The weighted difference across all of the studies revealed a reduction of a little less than half a symptom day per cold episode, representing an 8% to 9% reduction in symptom days. There was no clear indication of the relative benefits of different regimes or vitamin C doses. However in trials that tested vitamin C after cold symptoms occurred, there was some evidence that a large dose produced greater benefits than lower doses. REVIEWER'S CONCLUSIONS: Long term daily supplementation with vitamin C in large doses daily does not appear to prevent colds. There appears to be a modest benefit in reducing duration of cold symptoms from ingestion of relatively high doses of vitamin C. The relation of dose to therapeutic benefit needs further exploration.

Administration, Oral↗
PubMed2000

Behavioral assessment of visual acuity in mice and rats.

We have developed a simple computer-based discrimination task that enables the quick determination of visual acuities in rodents. A grating is displayed randomly on one of two monitors at the wide end of a trapezoidal-shaped tank containing shallow water. Animals are trained to swim toward the screens, and at a fixed distance, choose the screen displaying the grating and escape to a submerged platform hidden below it. Both mice and rats learn the task quickly. Performance falls below 70% when the spatial frequency is increased beyond 0.5 cycles in most C57BU6 mice, and around 1.0 cycles per degree (cpd) in Long-Evans rats.

Adaptation, Physiological↗
PubMed2000

Environmental enrichment from birth enhances visual acuity but not place learning in mice.

The effect of richness of the environment on behavioral function was investigated in C57B6 mice. Animals were raised in either enriched (group-housed in large clear plexiglas cages with stimulating objects) or restricted (group housed in opaque white plastic cages with no stimulating objects) environmental conditions and their spatial learning and visual acuity were measured as adults. The performance of enriched and restricted groups were indistinguishable in place and cued versions of the Morris water task; however, the visual acuity of the enriched group, measured in a grating versus gray version of the visual water task, was 18% higher than the restricted group. These data demonstrate that the function of the mouse visual system can be significantly influenced by the nature of early visual input. They also indicate that the effects of environmental enrichment are manifested differently in behavioral measures of spatial learning and visual acuity.

Animals↗
PubMed2000

Experience-dependent plasticity of visual acuity in rats.

Rats have become a popular model for investigating the mechanisms underlying ocular dominance plasticity; however, no quantitative assessment of the effects of visual deprivation on behavioural acuity has been reported in this species. We measured the spatial acuity of monocularly and binocularly deprived rats with a visual discrimination task. The average spatial acuity of normal rats and rats deprived of vision after postnatal day 40 was approximately 1 cycle/degree. Monocular deprivation up to postnatal day 40 resulted in a 30% decrease in acuity and there was no recovery after 8 months. Identical binocular deprivation produced a comparable but significantly smaller reduction in acuity. The deleterious effects of monocular and binocular deprivation on visual acuity indicate that the development of cortical receptive field properties related to spatial tuning are affected by both monocular and binocular deprivation. The similarities in the effects of visual deprivation on visual acuity between rats and other mammals confirm that rats are a good model system for studying the cellular and molecular mechanisms underlying experience-dependent visual plasticity.

Age Factors↗
PubMed2000

Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized, controlled trial.

BACKGROUND: Acute upper respiratory infections are common in children who attend child care, and preventing transmission of disease in this setting depends on actions by child care staff. We set out to discover whether transmission of respiratory infections in child care could be reduced by improved infection control procedures. METHODS: We performed a cluster, randomized, controlled trial of an infection control intervention conducted in child care centers in 1 city in Australia. The intervention was training of child care staff about transmission of infection, handwashing, and aseptic nosewiping technique. Implementation of the intervention was recorded by an observer. Illness was measured by parent report in telephone interviews every 2 weeks. RESULTS: There were 311 child-years of surveillance for respiratory symptoms. By multivariable analysis, there was no significant reduction in colds in intervention center children across the full age range. However, a significant reduction in respiratory illness was present in children 24 months of age and younger. When compliance with infection control practices was high, colds in these children were reduced by 17%. CONCLUSIONS: This trial supports the role of direct transmission of colds in young children in child care. The ability of infection control techniques to reduce episodes of colds in children in child care was limited to children 24 months of age and under.

Australian Capital Territory↗
PubMed2000

Effect of infection control measures on the frequency of diarrheal episodes in child care: a randomized, controlled trial.

BACKGROUND: Diarrheal infections are common in children who attend child care, and preventing transmission of disease in this setting depends on actions by child care staff. We set out to discover whether transmission of gastrointestinal infections in child care could be reduced by improved infection control procedures. METHODS: We performed a cluster randomized, controlled trial of an infection control intervention conducted in child care centers for 1 city in Australia. The intervention was training of child care staff about transmission of infection and handwashing and focused on both staff and child behavior. Implementation of the intervention was recorded by an observer. Illness was measured by parent report in telephone interviews every 2 weeks. RESULTS: There were 311 child-years of surveillance for diarrheal episodes. The rate of episodes of diarrhea was 1.9 per child-year in intervention centers and 2.7 per child-year in control centers. Multivariable analysis showed that diarrheal episodes were significantly reduced in intervention center children by 50%. However, the impact of the intervention was confined to children over 24 months of age. For those centers in which children's compliance with handwashing was high, diarrheal episodes were reduced by 66%. CONCLUSIONS: This trial supports education about infection control, for staff and children in child care, as a means of reducing transmission of diarrhea. Reduction in episodes of diarrhea in children in child care was limited to children over 24 months of age.

Australian Capital Territory↗
PubMed2000

Realities of practice. Engaging parents and GPs in developing clinical practice guidelines.

OBJECTIVE: To integrate evidence based medicine with the experience and expectations of consumers and GPs in the development of clinical practice guidelines for acute respiratory infections (ARI) in young children. METHOD: Focus groups and workshops were held with 21 GPs and 27 patients of young children involved in a 2 year randomised controlled trial. RESULTS: The acceptability of the guideline development process for participants was determined. Barriers were identified which would impede clinical change, including: inadequate time; lack of knowledge; fear of patient dissatisfaction; and fear of poor health outcome. CONCLUSION: This paper details a process of guideline development that addresses the realities of general practice in Australia and the concerns of consumers. We identified potential barriers to change and integrated intervention strategies with the evidence to produce realistic clinical practice guidelines.

Acute Disease↗
PubMed1999

Antibiotic resistance in Streptococcus pneumoniae isolated from children.

OBJECTIVE: To determine the level of antibiotic resistance in pneumoniae (S. pneumoniae) isolated from nasal swabs of healthy children. METHOD: Cross-sectional community survey. SETTING: Survey was undertaken in general practice settings in Canberra during March and April 1998. SUBJECTS: Four hundred and sixty-one children under 3 years of age enrolled in general practice trial of clinical practice guidelines for antibiotic use. OUTCOME MEASURES: Resistance to penicillin, erythromycin, co-trimoxazole, tetracycline, chloramphenicol and cefotaxime among the isolates of S. pneumoniae. RESULTS: A total of 461 nasal swabs were collected and S. pneumoniae was isolated from 171 (37.1%). Penicillin resistance was found in 12.3% of these isolates, with high level resistance in 0.6%. Resistance rates were higher for cotrimoxazole (44.4%) and erythromycin (18.1%) than for penicillin. Multidrug resistance was found in 19% of these isolates. There was a significant association between the attendance at a day care centre and carriage of pneumococcus (53% vs 32%, odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5-3.7, P < 0.001). Children who attended day care centers and had received antibiotics during the 4 months prior to swab collection were three times more likely to carry an antibiotic-resistant isolate than children who had neither attended a day care centre nor received antibiotics (68% vs 40%, OR 3.1, 95% CI 1.2-8.4, P = 0.02). CONCLUSION: The level of antibiotic resistance in pneumococci from healthy children was of concern. Carriage of pneumococcus was significantly higher in children who attended a day care centre. Resistance was significantly correlated with antibiotic use in combination with day-care attendance. These findings warrant more judicious use of antibiotics in children.

Cefotaxime↗
PubMed1999

Respiratory tract infections as a public health challenge.

Acute respiratory infections have everywhere become the province of clinicians and the pharmaceutical industry. A public health approach is needed with systematic efforts to minimize transmission, maximize prevention, and harness the research and surveillance effort to decrease their incidence and severity. These infections have a huge incidence, morbidity burden, and economic impact in all societies. Several factors now demand renewed attention to prevention. They include the growing costs and potentially limited benefits of an expanded pharmacotherapeutic approach; the serious change in antibiotic susceptibility of the common respiratory pathogens; the advances made in vaccinology in recent years; and the need to promote equity and share limited health resources across the world's population. Care should not be restricted to those in affluent countries who can afford increasingly expensive treatment.

Humans↗
PubMed1999

Vitamin C and acute respiratory infections.

So far over 60 studies have examined the effects of vitamin C on the common cold. No effect on common cold incidence was observed in the six largest studies, indicating that vitamin C has no preventive effects in normally nourished subjects in the Western countries. There are, however, smaller studies reporting benefit. In three trials of subjects under heavy acute physical stress, common cold incidence decreased by on average 50%, and in four trials of British males common cold incidence decreased by on average 30% in the vitamin C groups. The dietary vitamin C intake in the UK is low, and consequently the benefit may be due to the correction of marginal deficiency, rather than high vitamin doses. Regular vitamin C supplementation (> or =1 g/day) has quite consistently reduced the duration of colds, but the size of the benefit has varied greatly. In the four largest studies the duration of colds was reduced only by 5%. In two of these studies, however, absence from school and work was reduced by 14-21% per episode, which may have practical importance. Three controlled studies recorded a reduction of at least 80% in the incidence of pneumonia in the vitamin C group, and one randomised trial reported substantial treatment benefit from vitamin C in elderly UK patients hospitalized with pneumonia or bronchitis. It seems that the preventive effects of supplementation are mainly limited to subjects with low dietary vitamin C intake, but therapeutic effects may occur in wider population groups. Further carefully designed trials are needed to explore the effects of vitamin C.

Ascorbic Acid↗