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Biomedical subjects

R M Douglas

Publications and source records attributed to R M Douglas.

At least 109 records · Page 6Linked to original sources

Stress and acute respiratory infection.

To examine the relationship between stress and upper respiratory tract infection, 235 adults aged 14-57 years, from 94 families affiliated with three suburban family physicians in Adelaide, South Australia, participated in a six-month prospective study. High and low stress groups were identified by median splits of data collected from the Life Events Inventory, the Daily Hassles Scale, and the General Health Questionnaire, which were administered both before and during the six months of respiratory diary data collection. Using intra-study stress data, the high stress group experienced significantly more episodes (mean of 2.71 vs. 1.56, p less than 0.0005) and symptom days (mean of 29.43 vs. 15.42, p = 0.005) of respiratory illness. The two groups were almost identical with respect to age, sex, occupational status, smoking, passive smoking, exposure to air pollution, family size, and proneness to acute respiratory infection in childhood. In a multivariate model with total respiratory episodes as the dependent variable, 21% of the variance was explained, and two stress variables accounted for 9% of the explained variance. Significant, but less strong relationships were also identified between intra-study stress variables and clinically "definite" episodes and symptom days in both clinically definite and total respiratory episodes. Pre-study measures of stress emphasized chronic stresses and were less strongly related to measures of respiratory illness than those collected during the study. However, significantly more episodes (mean of 2.50 vs. 1.75, p less than 0.02) and symptom days (mean of 28.00 vs. 17.06, p less than 0.03) were experienced in the high stress group. In the multivariate analyses, pre-study stress remained significantly associated with total respiratory episodes and symptom days in total and "definite" respiratory episodes. In all of the multivariate analyses performed, sex (female) and age also appeared as important correlates of respiratory illness.

Adolescent↗

Vitamin A status in children who are prone to respiratory tract infections.

The effect of Vitamin A supplementation on susceptibility to acute respiratory infections was investigated in a randomized controlled trial. One hundred and forty-seven preschool-age children with a history of frequent respiratory illness were randomized into Vitamin A supplemented (450 micrograms/day) and placebo groups. Respiratory symptoms were recorded on a daily basis over a period of 11 months. The children who received the supplement experienced 19% fewer episodes of respiratory symptomatology (P less than 0.05) than their placebo counterparts, despite the fact that their plasma retinol levels did not change. Children with a prior history of lower respiratory illness or of allergy benefited most from supplementation. The plausibility of a role for Vitamin A in the aetiology of respiratory proneness is reviewed.

Child, Preschool↗

Correlation between long-term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

The relationship between long-term potentiation (l.t.p.) and the release of endogenous amino acid transmitters has been investigated in the dentate gyrus of rats anaesthetized with urethane. The molecular layer was perfused with artificial cerebrospinal fluid using a push-pull cannula. The perfusate was collected and analysed for glutamate, aspartate, glycine, glutamine and gamma-aminobutyric acid (GABA) using high-performance liquid chromatography (h.p.l.c.) with fluorometric detection. Recording electrodes were attached to the cannula to enable responses evoked by test stimuli to the perforant path to be monitored in the molecular and cell body layers. Perfusion was continued for 3 h while test stimuli were delivered to the perforant path at 30 s intervals. In the control group (n = 8), no further stimulation was given. In a second group (n = 8), a single high-frequency train (250 Hz for 200 ms) was delivered at the end of the first hour to induce l.t.p. The average potentiation of the slope of the excitatory post-synaptic potential (e.p.s.p.) 2 h later was 15%. In a third group (n = 8), the train to the perforant path was paired with a train to the commissural input to the dentate gyrus, a procedure which blocks the induction of l.t.p. In the potentiated group, there was an increase in the concentrations of glutamate and aspartate following the induction of l.t.p., relative to the decline seen in corresponding periods of the control group. This increase remained statistically significant for 1.5 h in the case of glutamate and for 45 min in the case of aspartate. There were no l.t.p.-associated changes in the release of glutamine or glycine; there was an indication that l.t.p. may be associated with a decrease in the release of GABA. Increasing the frequency and intensity of perforant path activation resulted in enhanced concentrations of glutamate and aspartate in the perfusate; no such changes occurred when granule cells were activated antidromically. We discuss the origin of the relative increases in the concentration of glutamate and aspartate which are found in the perfusate following the induction of l.t.p. and conclude that the most likely source is a sustained increase in activity-dependent release of these amino acids from perforant path terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

A time-based stereoscopic depth mechanism in the visual cortex.

We propose a new depth mechanism, operating in the visual cortex, which uses temporal as well as spatial cues. By varying the timing of input to the two eyes, and the position of stimuli on the two receptive fields, we show that both temporal and spatial disparities influence the binocular responses of single cortical cells.

Animals↗

Responses of single neurones in cat auditory cortex to time-varying stimuli: frequency-modulated tones of narrow excursion.

In the primary auditory cortex of cats anaesthetized with nitrous oxide, single neurones were examined with respect to their responses to tone bursts and linear modulations of the frequency of an on-going continuous tone. Using FM ramps of 2.0 kHz excursion and varying centre frequency, each of 39 neurones was examined for its preference for the direction of frequency change of a ramp whose centre frequency was varied in and around the neurone's response area. Direction preference was strictly associated with the slopes of the cell's spike count-versus-frequency function over the frequency range covered by the ramp. Preferences for upward- and downward-directed ramps were associated with the low- and high-frequency slopes of the spike count function, respectively. The strength of the cell's direction preference was associated with the relative steepness of the spike count function over the frequency range covered by the ramp. The timing of discharges elicited by the frequency modulations was found to be the sum of the cell's latent period for tone bursts plus the time after ramp onset that the stimulus frequency fell within the neurone's response area. The implications of these data for the processing of narrow and broad frequency-modulated ramps are discussed.

Animals↗

Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades.

The frontal eye field (FEF) and superior colliculus (SC) are thought to form two parallel systems for generating saccadic eye movements. The SC is thought classically to mediate reflex-like orienting movements. Thus it can be hypothesized that the FEF exerts a higher level control on a visual grasp reflex. To test this hypothesis we have studied the saccades of patients who have had discrete unilateral removals of frontal lobe tissue for the relief of intractable epilepsy. The responses of these patients were compared to those of normal subjects and patients with unilateral temporal lobe removals. Two tasks were used. In the first task the subject was instructed to look in the direction of a visual cue that appeared unexpectedly 12 degrees to the left or right of a central fixation point (FP), in order to identify a patterned target that appeared 200 ms or more later. In the second "anti-saccade" task the subject was required to look not at the location of the cue but in the opposite direction, an equal distance from FP where after 200 ms or more the patterned target appeared. Three major observations have emerged from the present study. Most frontal patients, with lesions involving both the dorsolateral and mesial cortex had long term difficulties in suppressing disallowed glances to visual stimuli that suddenly appeared in peripheral vision. In such patients, saccades that were eventually directed away from the cue and towards the target were nearly always triggered by the appearance of the target itself irrespective of whether or not the "anti-saccade" was preceded by a disallowed glance. Those eye movements away from the cue were only rarely generated spontaneously across the blank screen during the cue-target time interval. The latency of these visually-triggered saccades was very short (80-140 ms) compared to that of the correct saccades (170-200 ms) to the cue when the cue and target were on the same side, thereby suggesting that the structures removed in these patients normally trigger saccades after considerable computations have already been performed. The results support the view that the frontal lobes, particularly the dorsolateral region which contains the FEF and possibly the supplementary motor area contribute to the generation of complex saccadic eye-movement behaviour. More specifically, they appear to aid in suppressing unwanted reflex-like oculomotor activity and in triggering the appropriate volitional movements when the goal for the movement is known but not yet visible.

Adult↗

Alterations in response properties in the lateral and dorsal terminal nuclei of the cat accessory optic system following visual cortex lesions.

The response properties of cells in the lateral (LTN) and dorsal (DTN) terminal nuclei of the accessory optic system (AOS) were examined in 14 cats which underwent unilateral visual cortex ablation. Following decortication, single units in the LTN and DTN no longer showed the high degree of binocular convergence characteristic of the intact animal, but instead LTN and DTN units became almost completely dominated by the contralateral eye. In addition, responsivity of LTN and DTN cells to high stimulus velocities was abolished by removal of cortical input. This decrement in high velocity response was observed in both the excitatory and the inhibitory components of the velocity response profile. While the incidence of direction selective neurons in both the LTN or the DTN was not affected by decortication, the distribution of preferred and nonpreferred directions was dramatically altered in the LTN, and to a lesser extent in the DTN. In the LTN, there was a severe reduction in the number of cells which displayed maximal excitation for upward stimulus motion. Instead, most LTN units in the decorticate cat preferred downward directed stimulus motion. In the DTN, most units still preferred horizontal stimulus motion as in the intact animal, but the overall distribution of preferred directions displayed a clear downward vertical vector component. In other respects, such as receptive field size and position in visual space, on/off responses, and resting discharge rate, LTN and DTN units appeared unaffected by cortical lesions. These experiments demonstrate that the cortical input to the LTN and DTN plays a highly significant role in the formation of response properties of cells located in these nuclei. The results presented in this report indicate that the visual cortex is a major source of ipsilateral eye input, high velocity responses, and upward direction selectivity for the AOS units examined in these experiments.

Animals↗

Vaccination against Streptococcus pneumoniae in childhood: lack of demonstrable benefit in young Australian children.

A double-blind, randomized, controlled trial of a 14-valent Streptococcus pneumoniae polysaccharide vaccine, with saline as placebo, was performed on 1,273 healthy children six to 54 months of age. Different dosage regimens were used for children younger and older than two years of age. The vaccine was well tolerated. Follow-up continued for two years, during which time 95% of mothers submitted diaries of their children's respiratory-tract and otic symptoms. Data from diaries and medical and hospital case notes failed to reveal consistent or significant benefits in those who received the vaccine. In the first 16 months after immunization, recipients of placebo experienced an average of 0.69 episodes of otitis media per child, compared with 0.63 in recipients of vaccine (P = .6). Recipients of vaccine had no consistent reduction in days of respiratory morbidity, antibiotic consumption, hospitalization, or visits to a physician, when compared with recipients of placebo.

Australia↗

Eye-head coordination in cats.

Gaze is the position of the visual axis in space and is the sum of the eye movement relative to the head plus head movement relative to space. In monkeys, a gaze shift is programmed with a single saccade that will, by itself, take the eye to a target, irrespective of whether the head moves. If the head turns simultaneously, the saccade is correctly reduced in size (to prevent gaze overshoot) by the vestibuloocular reflex (VOR). Cats have an oculomotor range (OMR) of only about +/- 25 degrees, but their field of view extends to about +/- 70 degrees. The use of the monkey's motor strategy to acquire targets lying beyond +/- 25 degrees requires the programming of saccades that cannot be physically made. We have studied, in cats, rapid horizontal gaze shifts to visual targets within and beyond the OMR. Heads were either totally unrestrained or attached to an apparatus that permitted short unexpected perturbations of the head trajectory. Qualitatively, similar rapid gaze shifts of all sizes up to at least 70 degrees could be accomplished with the classic single-eye saccade and a saccade-like head movement. For gaze shifts greater than 30 degrees, this classic pattern frequently was not observed, and gaze shifts were accomplished with a series of rapid eye movements whose time separation decreased, frequently until they blended into each other, as head velocity increased. Between discrete rapid eye movements, gaze continued in constant velocity ramps, controlled by signals added to the VOR-induced compensatory phase that followed a saccade. When the head was braked just prior to its onset in a 10 degrees gaze shift, the eye attained the target. This motor strategy is the same as that reported for monkeys. However, for larger target eccentricities (e.g., 50 degrees), the gaze shift was interrupted by the brake and the average saccade amplitude was 12-15 degrees, well short of the target and the OMR. Gaze shifts were completed by vestibularly driven eye movements when the head was released. Braking the head during either quick phases driven by passive head displacements or visually triggered saccades resulted in an acceleration of the eye, thereby implying interaction between the VOR and these rapid-eye-movement signals. Head movements possessed a characteristic but task-dependent relationship between maximum velocity and amplitude. Head movements terminated with the head on target. The eye saccade usually lagged the head displacement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Acute tonsillitis in children: microbial pathogens in relation to age.

Tonsil swabs were collected from 248 children (1 through 10 yr) who presented with acute tonsillitis. A beta-hemolytic streptococcus was grown from 129 (53%) of 244 cases and as the sole pathogen from 83 (47%) of 178 cases. Beta-Hemolytic streptococci were especially common over the age of 6 yr (68% of children) relatively uncommon under the age of 4 yr (18%); most (90%) streptococci belonged to group A; 18 streptococcal T types were represented amongst 88 group A strains; the potentially nephritogenic serotypes 4 and 12 were prominent and accounted for 42 (47%) of typable isolates. Eight (8%) of 96 unmatched children (1 through 10 yr) who served as controls were found to be carrying beta-hemolytic streptococci, 5 of which belonged to group A. A virus was grown from 52 (29%) of 182 children and as the sole pathogen from 40 (22%) of 178 children. Only echoviruses (8 serotypes) and adenoviruses (5 serotypes) were common; younger children showed a higher isolation rate of viruses. The clinical picture in children yielding a virus was indistinguishable from that of cases who yielded a beta-hemolytic streptococcus.

Acute Disease↗

Commissural inhibition and facilitation of granule cell discharge in fascia dentata.

Stimulation of the contralateral hippocampus in the hilar region had a marked effect on granule cell excitability in the fascia dentata. The primary effect was to block the population spike that otherwise occurred in response to perforant path stimulation. In contrast, the size the excitatory post-synaptic potential component of the perforant path-evoked field potential was only slightly reduced. The population spike diminution began at short latency (3.5 msec), beginning at about 1.0 msec after the onset of the slow component of the potential evoked by the contralateral stimulus. The completeness and duration of this population spike diminution depended on the contralateral stimulus intensity. The maximum duration was less than 40 msec in unanesthetized rats and more than 100 msec in rats under pentobarbital anaesthesia. Bicuculline did not diminish the field potential evoked by the contralateral stimulus but it did prevent the stimulus from blocking the perforant path population spike and, instead, permitted a weak facilitation of the population spike. The normal reduction of the population spike was not mediated by recurrent inhibition, secondary to granule cell activation, since it occurred whether or not the granule cells were inhibited at the time of contralateral stimulation. These results imply that the initial main effect on fascia dentata granule cells of activity in the contralateral hilus is a gamma-aminobutyric-acid-mediated inhibition. This effect most probably involves commissural excitation of local inhibitory interneurons. The direct excitatory action of commissural fibers on granule cells, by comparison, is very weak.

Anesthesia, General↗

Antibody response to pneumococcal vaccination in children younger than five years of age.

Sera were analyzed by radioimmunoassay for type-specific pneumococcal antibody in 249 children aged six to 54 months, who were participating in a controlled trial of a 14-valent pneumococcal vaccine. Levels of serum antibody to all serotypes increased after immunization in all age groups tested. For all serotypes, the antibody response increased progressively with age whether response was viewed as antibody doubling, relative increase in geometric mean, or final antibody level. Responses were poor up to the age of five years for the important pediatric serotypes 6A, 14, 19F, and 23F. Seventeen children under the age of two years at the time of primary immunization received booster doses of vaccine six months later. There was no significant increase in antibody to any serotype, and the geometric mean antibody levels fell for most types. Immune response to the pediatric serotypes was poor until the age of 4.5 years.

Aging↗

Inhibitory modulation of long-term potentiation: evidence for a postsynaptic locus of control.

Long-term potentiation (LTP) of the excitatory synapses of the perforant path onto the granule cells of the fascia dentata was prevented, or greatly reduced in amount, by stimulation of the contralateral hilus, a source of the commissural afferents and an indirect source of granule cell inhibition. The LTP was reduced only when the onset of contralateral stimulation fell within 50 ms before and 1 ms after the onset of the perforant path conditioning train. Over this time interval, the ability of the volley from the contralateral hilus to block granule cell discharge (population spike) caused by the perforant path conditioning train varied, but not with a time course corresponding to the reduction of LTP. Although trains of impulses applied at high frequency (3-8 pulses at 400 Hz) were often able to block the perforant path LTP completely, single shocks strong enough to block the perforant path population spike were not sufficient to reduce LTP. The results support Marr's proposal that local inhibitory networks may set the threshold for producing long-term synaptic modification. They do not support Hebb's nor Uttley's proposal since the long-term synaptic modification did not depend on either the occurrence or the absence of a postsynaptic action potential.U

Anesthesia, General↗

Immunisation with a polyvalent pneumococcal vaccine. Effect of respiratory mortality in children living in the New Guinea highlands.

In Tari, in the southern highlands of Papua New Guinea, each child experienced, on average, two acute lower respiratory tract infections (ALRTI) between birth and age 5 years. The yearly mortality rate from ALRTI was 30 per 1000 in infants, and 4 per 1000 in children aged between 1 and 4 years. A double-blind trial of a 14-valent pneumococcal polysaccharide vaccine was carried out on 871 children from this community who were aged between 6 months and 5 years. Morbidity from ALRTI was lower (by 37%) in children given the vaccine provided they were at least 17 months of age at the time of immunisation. There were 8 deaths from ALRTI in the placebo group, but only 1 death in the vaccine group.

Acute Disease↗