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N MacLeod

Publications and source records attributed to N MacLeod.

17 recordsLinked to original sources
PubMed2002

Sea level and acute responses to hypoxia: do they predict physiological responses and acute mountain sickness at altitude?

OBJECTIVES: To compare a range of physiological responses to acute sea level hypoxia at simulated altitudes with the same physiological responses and acute mountain sickness (AMS) scores measured at altitude (similar to the simulated altitudes) during a 17 day trek in the Himalayas. METHODS: Twenty men and women aged 18-54 years took part in the study. End tidal CO(2) tension (PETCO(2)) and saturated oxygen (SaO(2)) were measured using a capnograph. Observations made at sea level and some simulated altitudes were compared with those in the Himalayas. Pairwise correlations were used to examine the correlation between variables and regression, with 95% prediction intervals providing information on how well one variable could be predicted from another for a given subject. RESULTS: There was only a significant correlation for a few comparisons. The 95% prediction intervals for individual SaO(2) values at a range of simulated altitudes were fairly wide going from +/- 4% to +/- 5%. All of the correlations between laboratory and Himalayan PETCO(2) values were not statistically significant. There was a significant correlation for the relation between SaO(2)and PETCO(2) at sea level for the laboratory data (r=-0.51; p=0.05). For the Himalayan data, there were significant correlations at Namche Bazaar (3450 m; day 3) (r=-0.56; p=0.01) and Dingboche (4300 m; day 6) (r=-0.48; p=0.03). The correlation between SaO(2) and PETCO(2) and AMS was generally poor. CONCLUSIONS: The results indicate that limited information can be gained on a subject's response to altitude by assessing physiological variables at sea level and a range of simulated altitudes before the subject carries out a trek at altitude.

Adolescent↗
PubMed1998

Electrophysiological properties of dorsal lateral geniculate neurons in brain slices from ME7 scrapie-infected mice.

Electrophysiological recordings using conventional intracellular techniques were obtained from dorsal lateral geniculate nucleus (dLGN) neurons in brain slices from ME7 scrapie-infected mice at specific time points throughout the incubation period of the disease. Comparisons were made with age-matched control mice. A number of dLGN neurons from control and scrapie-infected mice were injected with biocytin in order to examine their cellular morphology. Mice were infected with ME7 scrapie by an intraocular route and the mean (+/- SEM) incubation period of the disease was 276 +/- 3.5 days. Our results indicate that there were no differences in the electrophysiological or morphological parameters of neurons recorded in ME7 scrapie-infected and age-matched control mice at any stage of the disease up to 240 days postinoculation. After this time, however, no detectable electrical activity was recorded in the dLGN. This study demonstrates that in the ME7 scrapie-infected dLGN, relay neurons with normal physiological and morphological properties are present even at an advanced stage of the disease at a time when the dLGN is known to be subject to marked pathological changes and a profound neuronal loss.

Action Potentials↗
PubMed1998

Alterations in potassium currents may trigger neurodegeneration in murine scrapie.

Conventional electrophysiological intracellular recording techniques were used to test the hypothesis that enhanced calcium entry via voltage-gated calcium channels or the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor-channel complex may be a primary pathological mechanism triggering neurodegeneration in scrapie and related diseases. This study was carried out at a time when cell loss is known to occur and when hippocampal pyramidal cells in area CA1 are rendered hyperexcitable following scrapie infection. There was no change to the NMDA receptor-mediated component of the Schäffer collateral evoked excitatory postsynaptic potential (EPSP) or the level of spontaneous firing activity of CA1 cells following addition of the specific NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV, 20 microM), to the perfusate in scrapie-infected mice, indicating that the NMDA receptor-channel complex is not compromised by scrapie. There was also no change seen in the non-NMDA mediated component of the EPSP. The calcium spike of CA1 pyramidal cells was not significantly altered by scrapie infection, indicating that high threshold voltage-gated Ca2+ channel function is not compromised by scrapie. By contrast, cells from scrapie-infected mice fired calcium spikes repetitively and the long, slow AHP, which in control cells inhibited repetitive firing, was absent. Cells from scrapie-infected mice showed more depolarized membrane potentials than controls but this difference in potential was no longer observed after exposure to TEA. These data indicate a loss of TEA-insensitive and TEA-sensitive potassium conductances. We suggest that altered potassium currents rather than increased calcium entry via voltage-sensitive calcium channels or the NMDA receptor complex may be the primary pathological mechanism triggering neurodegeneration in scrapie and related diseases.

2-Amino-5-phosphonovalerate↗
PubMed1998

Synaptic plasticity in the CA1 area of the hippocampus of scrapie-infected mice.

Using conventional in vitro extracellular field potential recordings we have investigated both short- and long-term synaptic plasticity in the hippocampal CA1 area of mice infected with ME7 scrapie. In agreement with earlier studies, no changes were seen in the properties of the Schäffer collateralevoked field excitatory postsynaptic potential during the early stages of the disease (up to 160 days, post inoculation, d.p.i) after which time the recorded potentials were seen to attenuate. Also, up to this time no changes were seen in either paired-pulse facilitation or post-tetanic potentiation, which are short-term phenomena associated with brief elevations in presynaptic calcium levels. However, there was a significant shift from the ability of slices to maintain long-term potentiation (LTP) from 100 d.p.i. onwards. In all of these experiments short-term potentiation (STP) was preserved, suggesting that from the time that abnormal PrP becomes detectable, or perhaps even earlier, the mechanisms responsible for stabilizing the maintenance phase of LTP are impaired. This result is discussed in terms of the relationship between STP and LTP and how this might be compromised by the conversion of cellular prion protein (PrPC) to the scrapie, protease resistant form of PrP (PrPSc).

Animals↗
PubMed1997

Scrapie infection alters the membrane and synaptic properties of mouse hippocampal CA1 pyramidal neurones.

1. Electrophysiological recordings using conventional intracellular and extracellular techniques were made from the CA1 region of the hippocampus of ME7 scrapie-infected mice in a brain slice preparation at specific stages during the incubation period of the disease and compared with data obtained from age-matched control animals. 2. Extracellular field EPSP recordings in the stratum radiatum showed a gradual increase in the effective stimulus threshold and a reduction in amplitude of the response 5 months after inoculation with scrapie. Terminal animals showed a complete loss of the field EPSP. 3. Intracellular recordings from CA1 pyramidal cells of scrapie-infected animals after 5 months showed that the Schaffer collateral-evoked EPSP was attenuated, the effective stimulus threshold was increased and the rise time was slower in slices from scrapie-infected mice than in age-matched control mice. Inhibitory potentials evoked by the same stimulus also appeared weaker in scrapie-infected mice at this time. 4. To determine if the mechanisms of transmitter release during low-frequency stimulation of the Schaffer collaterals were altered in scrapie-infected mice, paired-pulse experiments were performed, but failed to show any differences between cells from scrapie-infected and control animals. 5. Pyramidal cells from scrapie-infected mice showed depolarized resting potentials and an increased membrane resistance compared with age-matched control cells. 6. The majority of scrapie-infected cells were spontaneously active, showing both single spike and bursting activity. The observed bursting activity was abolished and the spontaneous discharge rate of infected cells was markedly reduced by removing the CA3 area from the slice. 7. The action potential of cells from scrapie-infected mice showed a faster falling phase and larger amplitude fast and medium after-hyperpolarizations (AHPs) than age-matched control cells. In response to depolarizing current pulses cells from infected tissue showed a loss of early spike frequency adaptation. 8. Morphological observations of biocytin-labelled neurones confirmed our recordings were from pyramidal cells and showed that CA1 cells from scrapie-infected mice after 5 months showed a marked loss of dendritic spines and an abnormal dendritic morphology that included the appearance of vacuolar swellings. 9. The data show that membrane and synaptic abnormalities of the CA1 pyramidal neurones develop around 5 months after intracerebral infection of the mouse hippocampus with ME7 scrapie.

Action Potentials↗
PubMed1997

Properties of developing lateral geniculate neurones in the mouse.

This study describes the properties of neurones recorded in vitro from the dorsal lateral geniculate nucleus (dLGN) of the mouse between developmental stages E16 and P36 and represents the first systematic study of the development of rodent thalamic neurones. The results demonstrate that thalamo-cortical neurones in the mouse dLGN undergo a series of important changes as they mature. Prenatally recorded cells had low resting potentials and could not generate action potentials but as they mature, mouse dLGN neurones become more polarised and show an increase in membrane time constant and spike threshold, while action potentials increase in amplitude and decrease in width. The low-threshold spike (LTS) complex appears at the time of birth, but does not show properties typical of adult cells until at least the third postnatal week. Immature action potentials are primarily sodium-dependent but gain a significant calcium component in the second postnatal week, which is associated with a supra-threshold oscillation of the membrane potential. The electrical activity during this critical period is strongly influenced by the interaction of powerful inward and outward rectification with calcium conductances which determines the appearance of voltage responses to intracellular current injection. The membrane potential in recordings from neurones during the first postnatal week was dominated by intense TTX-sensitive depolarising synaptic-like events which attained amplitudes of 60 mV in several neurones at stages P5-P8. These changes are discussed in relationship to the formation of appropriate connections in the developing visual system.

Aging↗
PubMed1996

Increased use of cardiovascular medications in seniors prescribed non-ASA non-steroidal anti-inflammatory drugs.

The objective of this study was to determine the relationship between the prescribing of non-ASA non-steroidal anti-inflammatory drugs (NANSAID) and the prescribing of select cardiovascular (CV) medications. We performed a retrospective, cross-sectional analysis of the prescribed use of these medications between December 1, 1990 and June 30, 1991 by Albertans 65 years of age and older utilizing data from the publically-funded drug benefit plan. Variables examined were: the number of individuals prescribed NANSAID and CV medications; mean daily dose for these medications; calculated relative dose; the proportion of NANSAID users prescribed CV medications compared to non-users; and the relative proportions of users of specific NANSAID prescribed CV medication. We found that 33.4% and 19.6% of Albertan seniors were prescribed CV medications and NANSAID, respectively. NANSAID users were twice as likely to be prescribed CV medications as compared to non-users. Intermediate/high dose NANSAID users were more likely to be prescribed a CV medication as compared to low-dose users. The risk of being prescribed a CV medication was highest for indomethacin and users of multiple NANSAID, while ibuprofen users had the lowest risk. We conclude that NANSAID users are more likely to be also prescribed CV medications. Subjects who consume a lower dose of NANSAID are less likely to be prescribed CV medications. For different NANSAID, there is a spectrum of risk.

Age Factors↗
PubMed1994

Prescription of nonsteroidal anti-inflammatory drugs for elderly people in Alberta.

OBJECTIVE: To examine the extent prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) are used by elderly people in Alberta as well as the degree of concurrent use of multiple NSAIDs, of peptic ulcer medications and of certain medications known to have clinically significant adverse interactions with NSAIDs. DESIGN: Retrospective analysis of the Alberta Blue Cross database. SETTING: Alberta. PATIENTS: All people 65 years of age and older using the subsidized drug benefit plan for whom prescription claims were submitted for reimbursement between Jan. 1 and June 30, 1991. OUTCOME MEASURES: Number of people who received one or more prescriptions for NSAIDs, rates of prescribing peptic ulcer medications and drugs with the potential for clinically significant interactions with NSAIDs among NSAID users and non-NSAID users, and rate of prescribing more than one NSAID concurrently. RESULTS: Of the Albertan population 65 years of age and over 61,601 (26.7%) received at least one prescription for an NSAID during the study period. In decreasing order, the five most commonly prescribed NSAIDs were acetylsalicylic acid, diclofenac, naproxen, indomethacin and ibuprofen. The total cost of NSAID therapy was $5,415,974. Of the people prescribed an NSAID 25.8% were also prescribed a peptic ulcer medication, as compared with 10.5% of the non-NSAID users. There was a significant relation between the increasing number of NSAID prescriptions and the likelihood of receiving a peptic ulcer medication. Those who received a prescription for an NSAID were more likely than non-NSAID users to have been prescribed coumarin anticoagulants, diuretics, angiotensin-converting-enzyme inhibitors, beta-blockers, oral corticosteroids, methotrexate and lithium, all of which are known to have possible adverse interactions with NSAIDs. A total of 2,631 people had two or more prescriptions for NSAIDs filled on the same day. CONCLUSIONS: NSAIDs are prescribed frequently for elderly people and are associated with an increased likelihood of concurrent prescription of peptic ulcer medication and medications that could have adverse drug interactions with NSAIDs. Additional study is required to evaluate the appropriateness of NSAID use in elderly patients, to determine the degree of actual patient consumption of these medications, to document the true prevalence of clinically significant drug interactions and to formulate educational strategies to reach physicians with this information.

Aged↗
PubMed1989

The influence of the estrous cycle on the activity of striatal neurons recorded from freely moving rats.

Recordings from striatal neurons in conscious rats at various stages of the estrous cycle revealed differences in the activity of the neurons. Average firing rate was higher in diestrus than in animals in estrus or proestrus. The increase did not seem to depend on the motor activity of the animals nor was it present in ovariectomized rats. Since application of estrogen to ovariectomized rats did not change the firing rate of the neurons, we conclude that differences during the cycle in conscious rats are not mediated by an action of estrogen unlike those seen in anesthetized rats. Differing electrode sampling bias in the two situations, or an action of anesthetic in revealing the estrogen effect may explain the differences.

Action Potentials↗
PubMed1989

Triazolam.

Explore the source record for details and available documents.

Humans↗
PubMed1985

Electrophysiological properties of single units in dopamine-rich mesencephalic transplants in rat brain.

Electrophysiological recordings were made from grafts of embryonic ventral mesencephalon transplanted into the neocortex, overlying the host neostriatum of rats in which the intrinsic striatal dopamine (DA) innervation had been removed by a unilateral 6-hydroxydopamine (6-OHDA) lesion. Whereas all rats had surviving grafts, half of the rats showed recovery from amphetamine-induced rotational asymmetry induced by the 6-OHDA lesions ('compensation'), indicating a functional dopaminergic reinnervation of the host striatum by the graft. The electrophysiological recordings revealed: neurons within all grafts which could be antidromically activated from host striatum, and which had faster conduction velocities and narrower action potentials than is characteristic of DA neurons in the intact substantia nigra, neurons only within the grafts of compensated rats which had properties characteristic of normal nigral DA neurons, and neurons within the grafts which responded to stimulation of the frontal cortex and lower brainstem of the host. The data support the view that the grafts can establish physiologically functional afferent and efferent connections with the host brain.

Animals↗
PubMed1981

Electrophysiology of olfacto-limbic-hypothalamic connections in the pig.

To analyse fibre connections between the olfactory bulb (OB) and limbic-hypothalamic structures, the lateral olfactory tract (LOT) was stimulated electrically and extracellular action potentials were recorded from single units in the OB, the cortico-medial portion of the amygdala (AMY) and the mediobasal hypothalamus (MBH). More than 29% of the antidromically identified mitral cells in the OB showed a spontaneous episodic firing pattern consisting of alternating periods of activity and inactivity. Nearly 14% of the orthodromically excited non-mitral cells showed the same phasic firing pattern. 2.9% of AMY neurons were antidromically activated by LOT stimulation, whereas more than 52% showed orthodromic responses. In contrast to the AMY no neuron in the MBH could be antidromically invaded by electrical stimulation. The incidence of orthodromic responses was much less in the MBH when compared to the AMY (13.5%). It is concluded that the firing pattern of OB cells in the pig is complex, often phasic and unrelated to respiration or sniffing. The main OB is more closely related to the AMY than to the MBH. It is suggested that olfactory information is probably transmitted to the MBH via the AMY. The AMY may play a role in the regulation of OB activity.

Amygdala↗