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Biomedical subjects

J Duffin

Publications and source records attributed to J Duffin.

At least 73 records · Page 4Linked to original sources
PubMed1995

Activity of respiratory neurons during hypoxia in the chemodenervated cat.

Exposure of anesthetized paralyzed vagotomized peripherally chemodenervated cats to hypoxia results in initial depression and subsequent loss of the phrenic neurogram. To determine whether hypoxic respiratory depression results from the inhibition of respiratory premotor neurons by bulbospinal neurons of the Bötzinger complex (Böt-E neurons), extracellular recordings were made of dorsal and ventral respiratory group bulbospinal inspiratory neurons and Böt-E neurons during acute hypoxic hypoxia. All neurons recorded decreased firing rate during hypoxia. Böt-E neurons became silent before the loss of phasic phrenic activity during hypoxia and commenced firing before or coincident with the return of the phrenic neurogram during reoxygenation. Inspiratory neurons ceased firing coincident with phrenic silence. Dorsal respiratory group and ventral respiratory group neurons that had a late onset of firing with respect to the phrenic neurogram during normoxia fired progressively earlier in inspiration during hypoxia, an effect that was reversed during reoxygenation. These data are consistent with inhibition and/or disfacilitation as the mechanism of hypoxic respiratory depression but suggest that Böt-E neurons are not the source of this inhibition.

Animals↗
PubMed1994

Excitation of upper cervical inspiratory neurones by vagal stimulation in the cat.

The responses of 57 upper cervical inspiratory neurones to single shock stimuli applied to the ipsilateral cervical vagus nerve were recorded using peri-stimulus histograms in 19 cats. Many (47%) of the histograms showed a late latency (17.9 +/- 3.4 ms; mean +/- S.D.) broad peak following the stimulation preceding a similar peak in the histogram for the phrenic activity. Nine (16%) showed a short latency (5.2 +/- 1.2 ms) peak preceding that for the phrenic activity. These peaks were of narrow half-amplitude width (1.0 +/- 0.4 ms), indicative of a paucisynaptic pathway between the cervical vagus and the ipsilateral upper cervical inspiratory neurones. Such results suggest that the upper cervical inspiratory neurones are either monosynaptically excited via vagal fibres, or disynaptically excited via dorsal group inspiratory neurones.

Animals↗
PubMed1994

Ventilatory responses to exercise performed below and above the first ventilatory threshold.

These experiments examined the changes in ventilation at the start and end of exercise. Six subjects walked on a treadmill at two work rates above and two below that corresponding to their first ventilatory thresholds, for three durations. The subjects also exercised at the lowest and highest work rates while inspiring oxygen-enriched air. The group mean results showed that the abrupt increases in ventilation at the start of exercises at work rates above that of the first ventilatory threshold were greater than those below, but did not vary with duration or work rate either above or below. The abrupt falls in ventilation at the end of the exercises were less than the increases at the start. At work rates above that of the first ventilatory threshold, increases in work rate and duration were found to reduce the abrupt falls. The time constants of exponential curves fitted to the post-exercise declines in ventilation increased with work rate, and also with duration for work rates above that of the first ventilatory threshold. Finally, breathing oxygen enriched air did not alter any of these variables. These findings were interpreted as showing that the fast neural exercise drive is enhanced at work rates above that of the first ventilatory threshold, and becomes progressively less as exercise continues, a process exaggerated at higher work rates. In addition, the time course of the decline in ventilation following exercise, although altered by work rate and duration, was independent of the level of oxygenation.

Adult↗
PubMed1994

Coincidental changes in ventilation and electromyographic activity during consecutive incremental exercise tests.

These experiments examined the effect of metabolic acidosis, induced as a result of dynamic exercise, on ventilation, lactate concentration and electromyographic activity. Seven subjects performed two consecutive incremental exercise tests until volitional exhaustion was achieved. The two tests were identical and were separated by a 7-min period of light exercise. During the tests, ventilation, mixed expired oxygen and carbon dioxide, arterialized venous blood and electromyographic activity from the vastus lateralis was sampled. The results showed that the ventilation and electromyographic measurements followed a similar time course during both tests, although ventilation during the initial 6 min of the second test was significantly greater than the values recorded during the first test. In addition, throughout the first test lactate concentration increased with time, and pH, bicarbonate concentration and partial pressure of carbon dioxide decreased. In contrast, during the second test, lactate concentration decreased, and pH and bicarbonate concentration increased; during a period of time when ventilation and electromyographic activity were increasing. These findings have led us to conclude that changes in ventilation and electromyographic activity observed during incremental exercise are not related to changes in blood lactate concentration. It is suggested that such a conclusion supports the hypothesis that the changes in ventilation are mediated by an increase in neural activity originating from the subthalamic motor region or exercising limbs, induced in response to the need to progressively recruit fast twitch muscle fibres as exercise work rate is increased and as individual muscle fibres begin to fatigue.

Adult↗
PubMed1994

The ventilation, lactate and electromyographic thresholds during incremental exercise tests in normoxia, hypoxia and hyperoxia.

These experiments examined the effect of hypoxia and hyperoxia on ventilation, lactate concentration and electromyographic activity during an incremental exercise test in order to determine if coincident chances in ventilation and electromyographic activity occur during an incremental exercise test, despite an enhancement or reduction of peripheral chemoreceptor activity. In addition, these experiments were completed to determine if electromyographic activity and ventilation are enhanced or reduced in response to the inspiration of oxygen-depleted and oxygen-enriched air, respectively. Seven subjects performed three incremental exercise tests, until volitional exhaustion was achieved, while inspiring air with a fractional concentration of oxygen of either 66%, 21% or 17%. In addition, another single subject completed two tests while inspiring air with a fractional concentration of either 17% or 21%. During the tests, ventilation, mixed expired oxygen and carbon dioxide, arterialized venous blood and the electromyographic activity from the vastus lateralis were sampled. From these values ventilation, electromyographic and lactate thresholds were detected during normoxia, hypoxia and hyperoxia. The results showed that although ventilation and lactate concentration were significantly less during hyperoxia as compared to normoxia or hypoxia, the carbon dioxide production values were not significantly different between the normoxic, hypoxic and hyperoxic conditions. For a particular condition, the time, carbon dioxide production and oxygen consumption values that corresponded to the ventilation and electromyographic thresholds were not significantly different, but the values corresponding to the lactate threshold were significantly less than those for the electromyographic and ventilation thresholds. Comparisons between the three conditions showed that the time, carbon dioxide production and oxygen consumption values corresponding to each of these thresholds were not significantly difficult.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

AIDS, memory and the history of medicine: musings on the Canadian response.

This paper presents the history of AIDS in Canada with special attention to epidemiology, public policy, and social commentary. The interest in medical history sparked by the epidemic is studied in relation to its impact on public health measures. Conversely, the impact of the disease itself on the history of medicine is examined. AIDS seems to have had a greater impact on history in Canada than history has had on the Canadian response to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Neural drives to breathing during exercise.

This article presents the author's views about the neural drives to breathing during exercise. Two hypotheses are developed, the first being that the rapid changes in ventilation at the start and end of exercise are due to a fast neural drive whose magnitude is related to the frequency of limb movement. Experimental data are presented that this drive persists throughout exercise but declines as exercise continues. Second, the excessive increase in ventilation that occurs above the first ventilatory threshold during an incremental exercise test is due to a heavy exercise neural drive whose magnitude is related to the motor commands to the exercising muscles. Using the electromyographical activity of the working muscles as an index of the strength of the motor commands, experimental evidence is presented showing the coincidence of the first ventilatory threshold and that for the electromyographic activity of the working muscles during incremental exercise tests.

Animals↗
PubMed1994

Entrained breathing and oxygen consumption during treadmill walking.

Entrainment of the breathing rhythm to that of the rhythm of limb movement during exercise has been shown to decrease oxygen consumption for cycling at a moderate workload. This study examined the effect of entrainment on oxygen consumption during treadmill walking at two workloads. For each workload, 8 subjects performed two exercise protocols consisting of walking on a treadmill for 8 min. For the first protocol they received no instructions, but for the second protocol they were instructed to coordinate one breath per auditory cue which was provided during the last 4 min of exercise. The auditory cue was transmitted as a click via headphones. It was derived from a foot switch and was designed to synchronize breathing to the walking pace at a respiratory frequency close to that observed in the first protocol. Entrainment and oxygen consumption were compared between the protocols for the last 4-min segments for each workload. These comparisons showed that the presence of the auditory cue significantly increased entrainment from 29 to 74%, but oxygen consumption was not significantly changed.

Acoustic Stimulation↗
PubMed1993

Bötzinger expiratory neurones inhibit propriobulbar decrementing inspiratory neurones.

Although bulbospinal, expiratory neurones of the Bötzinger complex (BOT E-AUG) are known to have monosynaptic inhibitory connections to many bulbospinal respiratory neurones, their connections to propriobulbar respiratory neurones have not been so well characterized. We stimulated BOT E-AUG neurones with trains of pulses, and found an inhibition of medullary and phrenic respiratory activity with phase resetting. We also examined the response of propriobulbar, decrementing, inspiratory neurones (I-DEC) to the antidromic activation of BOT E-AUG neurones from the C3 segment of the spinal cord with single shocks and found evidence for a monosynaptic inhibition of the I-DEC neurones in the post-stimulus histograms of the extracellular firing. These results were obtained in 11 pentobarbital anaesthetized cats, and provide experimental support for a recent model of respiratory rhythmogenesis.

Animals↗
PubMed1993

Upper cervical inspiratory neurons in the rat: an electrophysiological and morphological study.

Upper cervical inspiratory neurons from a distinct neuronal column located near the lateral edge of the intermediate grey matter in the rostral spinal segments. Previous studies conducted in cats have demonstrated synaptic inputs to these neurons from several respiratory-related regions of the medulla, and long descending axonal projections mainly towards the motoneurons supplying the intercostal muscles. The aim of this study was to examine the electrophysiological and morphological properties of this propriospinal system in the rat. Extracellular recordings were made from 127 cervical inspiratory units, mainly in the C1 and C2 segments. Eighty-two percent could be antidromically activated from the C7/C8 border. No evidence of monosynaptic connection was obtained by cross-correlating the activity of some of these units with the discharge of the phrenic nerve. Intracellular recordings were made from seven neurons, three of which were labelled with biotinamide (neurobiotin). Long "survival times" after intracellular injections (up to 23 h) resulted in staining of axons for long distances, at least to the C5 segment. Each of the three labelled axons issued only one short collateral which arborized in the region of the phrenic nucleus. These results demonstrate that upper cervical inspiratory neurons in the rat have features similar to those previously described in the cat, including only a limited projection to the phrenic nucleus. In addition, this study provides the first morphological identification of these neurons.

Animals↗
PubMed1993

Axonal projections and synaptic connections of C5 segment expiratory interneurones in the cat.

1. Respiratory interneurones in the C4-C6 segments of the spinal cord have only recently been described; until now their projections and connections were not known. We investigated expiratory interneurones in the C5 spinal segment, using antidromic mapping to trace their projections and spike-triggered averaging to test their synaptic connections with phrenic motoneurones. 2. A total of seventy expiratory interneurones were recorded in nineteen cats anaesthetized with pentobarbitone, paralysed and ventilated. The interneurones were found scattered dorsomedial to the phrenic motor nucleus, with discharge patterns of a constant (66%), augmenting (24%) or decrementing (10%) type. 3. Interneurone axons were found in the ipsilateral ventrolateral funiculus using antidromic activation at thresholds < 20 microA. The axons of eighteen of thirty-three interneurones tested (55%) were found to extend to the rostral part of the C6 segment, seventeen of thirty-three (52%) to the caudal part of the C6 segment and ten of nineteen (53%) to the rostral part of the C7 segment. 4. Axon collaterals for thirteen of thirty-three interneurones (39%) were found in the ipsilateral half of the C6 segment, with their endings near the phrenic motor nucleus. In three cases two collaterals were found. None of the interneurones had projections in the contralateral halves of the C5 or C6 segments. 5. In a separate group of thirty-four expiratory interneurones, antidromic mapping was used to find an axon collateral in the C6 segment prior to spike-triggered averaging. Eleven of these interneurones had collaterals (32%) and were subsequently tested for synaptic connections to thirty-two phrenic motoneurones. In three separate instances (9%), inhibitory postsynaptic potentials were observed. Amplitudes, fall times and half-amplitude widths of the inhibitory postsynaptic potentials were 6.7, 10.4 and 10.6 microV; 0.3, 0.5 and 0.7 ms and 0.6, 1.6 and 3.3 ms respectively. 6. We conclude: (i) there is a population of expiratory interneurones in the C5 segment, located predominantly dorsomedial to the phrenic motor nucleus; (ii) at least one-half of these interneurones have ipsilateral intersegmental projections to the C6 segment and (iii) although synaptic connections from expiratory interneurones in the C5 segment to phrenic motoneurones in the C6 segment may be rare, the observed inhibitory postsynaptic potentials had fall times and latencies commensurate with monosynaptic connections.

Animals↗
PubMed1992

The death of Sarah Lovell and the constrained feminism of Emily Stowe.

In 1879 a coroner's inquest was held on the body of Sarah Lovell, a young, unmarried woman who was thought to have died of an attempt at procuring an abortion. Suspicion fell on Emily Stowe, Toronto's first woman doctor. Stowe had graduated 12 years earlier from a US medical college but had not yet been granted a licence to practise in Ontario. She admitted to having seen and spoken to Lovell but denied any involvement in an abortion. Less than a year later she obtained the long-desired licence. The author has used newspapers, journals and other archival sources to explore the nature of Stowe's testimony and its relation to her acceptance by the profession.

Abortion, Legal↗
PubMed1992

Characterization of the original Christmas disease mutation (cysteine 206----serine): from clinical recognition to molecular pathogenesis.

Christmas disease was first reported as a distinct clinical entity in two manuscripts published in 1952. The eponym associated with this disorder, is the surname of the first patient examined in detail and reported by Biggs and colleagues in a paper describing the clinical and laboratory features of seven affected individuals. This patient has severe factor IX coagulant deficiency (less than 0.01 units/ml) and no detectable circulating factor IX antigen (less than 0.01 units/ml). Coding sequence and splice junctions of the factor IX gene from this patient have been amplified in vitro through the polymerase chain reaction (PCR). One nucleotide substitution was identified at nucleotide 30,070 where a guanine was replaced by a cytosine. This mutation alters the amino acid encoded at position 206 in the factor IX protein from cysteine to serine. The non conservative nature of this substitution, the absence of this change in more than 200 previously sequenced factor IX genes and the fact that the remainder of the coding region of this gene was normal, all provide strong circumstantial evidence in favour of this change being the causative mutation in this patient. The molecular characterization of this novel mutation in the index case of Christmas disease, contributes to the rapidly expanding body of knowledge pertaining to Christmas disease pathogenesis.

Amino Acid Sequence↗
PubMed1992

Role of upper cervical inspiratory neurons studied by cross-correlation in the cat.

Axonal projections and synaptic connectivity of upper cervical inspiratory neurons (UCINs) were investigated in anaesthetised cats to clarify their role as propriospinal respiratory interneurons. Antidromic mapping showed axonal collaterals near phrenic and intercostal motonuclei. Of the UCINs tested, 37% had collaterals at T3-4; 55% had ipsilateral projections and 45% had contralateral projections. Ipsilateral or contralateral cross-correlations of the activity of pairs of UCINs (one on each side of the spinal cord) with the discharge of internal intercostal, external intercostal (T3-4) or phrenic nerves revealed similar features. Those with the internal intercostal and phrenic nerves were interpreted as evidence for shared or oligosynaptic excitation, those with the external intercostal nerve as shared excitation and inhibition. No evidence for monosynaptic connections was found. Monosynaptic connections could also not be demonstrated between inspiratory intercostal neurons located near (less than 0.5 mm) the UCINs collateral arborizations in T3-4, examined by cross-correlation. Afferent feedback from internal intercostal nerves (T3-4) was investigated by cross-correlating nerve stimulation with UCINs activity. Ipsilateral and contralateral cross-correlograms had similar features, providing evidence for excitation in some cases and inhibition in others. Finally, cross-correlations between ipsilateral UCINs and cervical sympathetic nerves were featureless. The results suggest that the role of UCINs as part of a respiratory propriospinal control system analogous to forelimb motor control is untenable, although they may be part of an intercostal afferent feedback loop.

Action Potentials↗
PubMed1992

Changes in ventilation in response to ramp changes in treadmill exercise load.

These experiments examined the changes in ventilation during a 40-s ramp increase in exercise load, produced by increasing either the speed of the treadmill or the grade, to equivalent end-points of oxygen uptake. Six subjects underwent five trials each for grade and speed, while ventilation was monitored breath-by-breath. For each subject, ventilation versus time for all five of the speed trials was plotted on a single graph and fitted by linear regression. The data for the grade trials were similarly treated. For all subjects, the slope of the regression line for the speed plots was found to be significantly (P < 0.05) greater than that for the grade plots. We concluded that these experimental results support the hypothesis that the neural drive to ventilation persists as exercise continues and is proportionately related to the frequency of limb movement.

Adult↗
PubMed1992

Changes in ventilation at the start and end of moderate and heavy exercise of short and long duration.

These experiments examined the effect of exercise intensity and duration on the magnitude of the abrupt change in ventilation at the start (VE,start) and end (VE,end) of exercise. Five subjects performed constant load treadmill exercise at 50% and 80% of their maximum oxygen consumption (VO2max) for 6 and 10 min while inspiring atmospheric air. The subjects also completed additional exercise tests at 80% VO2max for 10 min while inspiring an oxygen-enriched gas mixture. During each exercise trial ventilation was measured breath-by-breath. The VE,start and VE,end were determined by using non-linear curve-fitting techniques. The results showed that VE,start was greater at the start of the 80-% exercise tests compared to the 50-% tests and that VE,start at each level of exercise was greater than VE,end. The results also demonstrated that VE,end was inversely related to the intensity and duration of exercise. Furthermore, the VE,end was not altered subsequent to the inspiration of oxygen-enriched air. These findings have led us to postulate that the stimulus responsible for VE,start is reduced during exercise and that the degree of reduction is related to the intensity and duration of exercise. In addition, it was concluded that these changes might occur independently of peripheral chemoreceptor activity.

Adult↗