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C Nicholson

Publications and source records attributed to C Nicholson.

At least 19 recordsLinked to original sources
PubMed1992

Quantitative analysis of extracellular space using the method of TMA+ iontophoresis and the issue of TMA+ uptake.

The tetramethylammonium (TMA+) method for measuring the volume fraction and tortuosity of brain extracellular space is presented in detail. The temporal and spatial distribution of TMA+ in the extracellular space following iontophoresis or pressure microinjection is described by suitable equations and illustrated with graphs. By fitting the equations to the concentration versus time data obtained from measurements with ion-selective micropipettes, the volume fraction and tortuosity can be measured. In addition, the concentration-dependent uptake of TMA+ can be estimated from the given equations. The final section of the paper derives simple numerical estimates of TMA+ loss from the extracellular space by this mechanism.

Animals↗
PubMed1992

Fat distribution and blood lipids in a sample of healthy elderly people.

The cross-sectional sample consisted of data for 41 white men and 63 white women, 67-92 years of age who were healthy volunteer participants in the Aging Process Study at the University of New Mexico School of Medicine in Albuquerque, New Mexico. The variables consisted of anthropometric measures of body fatness, blood lipids and blood pressures. Correlations were computed between principal component scores, ratios of body circumferences, W/S2, blood lipid values and blood pressures for each sex. In the men, the significant correlations were of the abdomen/hip and abdomen/thigh ratios with W/S2, and the principal component scores with HDL cholesterol, triglyceride and systolic blood pressure. In the women, the abdomen/hip ratio had a low negative correlation with HDL cholesterol but a low positive correlation with triglyceride levels. The principal component scores also had low correlations with blood pressure and triglycerides. Multiple regressions were used to determine further associations between risk factors and fat distribution indices. In the men, the relationships of age and levels of body fatness with HDL cholesterol were much stronger and more complex than those with triglyceride or systolic blood pressure. In the women, only HDL cholesterol and triglyceride were associated with abdomen/hip ratio after removing the effects of overall fatness. The present findings indicate that a large abdominal circumference, implying a correspondingly large internal adipose tissue deposit, produces negative health alterations in blood lipid levels in this sample of elderly individuals. In younger adults, these changes are considered to increase the risk for cardiovascular disease.

Adipose Tissue↗
PubMed1991

Threshold extracellular concentration distribution of penicillin for generation of epileptic focus measured by diffusion analysis.

The tissue volume required to produce a penicillin-induced interictal discharge in the local EEG was estimated. A pair of microelectrodes were lowered into the motor cortex of anaesthetised and artificially ventilated rats. One double-barrelled electrode was used to release tetramethylammonium (TMA+) by iontophoresis or to pressure eject a solution containing penicillin (PEN-) and TMA+ concentration. The extracellular distribution of PEN- was defined using diffusion analysis of the TMA+. From these data the spatial distribution of PEN- was estimated at the times of first interictal spikes in the EEG. The critical mass of active nerve cells was calculated from the threshold concentration of PEN- needed to elicit paroxysmal depolarisation shifts in neocortical slices and found to lie within a tissue sphere with a radius of ca. 150 microns.

Animals↗
PubMed1991

Mothers' reports of childhood vaccinations and infections and their concordance with general practitioner records.

Mothers of 294 children aged 3-9 years were interviewed about their child's previous history of vaccinations and infections. The study group comprised healthy children selected at GP surgeries (n = 136) and those hospitalized for both minor and serious conditions (n = 168). The results evaluate the entire study group for the pattern of reporting vaccinations and infectious episodes under three years of age, comparing two different data sources-mothers' reports and GP records. Maternal recall accuracy is formally tested (Kappa statistic) for agreement with GP records. For vaccination history the results indicate that mothers and GPs are inadequate data sources, and suggest use of computerized health district records to improve data accuracy. Major differences on infectious history were evident for two types of questions-closed for specific infections and open-ended for 'other infections'. Specific infections (e.g. measles) were systematically over-reported by mothers compared with GP records, but mothers failed to 'time' the event. Concordance for 'other infections' was also poor, but, by contrast, GPs systematically over-recorded this range of infections, indicating substantial inaccuracy in mothers' recall. The authors suggest that GP records should be the preferred source of data for these 'other' infectious episodes, especially under one year of age. Improved questionnaire design would elicit more accurate maternal reports on specified infections for which a GP may well not be consulted and corroboration would be impossible.

Case-Control Studies↗
PubMed1991

Iris colour and the influence of local anaesthetics on pre-corneal tear film stability.

Using non-invasive methods we report here that the stability of the pre-corneal tear film is lower in the brown eye than in the blue eye. The average stability in the blue eye is 15.8 sec (SD +/- 5.8) and in the brown eye it is 12.3 sec (SD +/- 2.9). On average, instillation of topical anaesthetics, benoxinate hydrochloride (0.4%) or amethacaine hydrochloride (0.5%), depress the stability of the pre-corneal tear film in blue eyes but not in brown eyes.

Administration, Topical↗
PubMed1991

Extracellular volume decreases while cell volume is maintained by ion uptake in rat brain during acute hypernatremia.

1. Regulation of brain extracellular and intracellular water content, regarded as volume, and electrolytes in response to 90 min of hypernatremia has been studied in the cerebral cortex of rats under urethane anaesthetic. 2. Total tissue electrolytes and water were partitioned between extracellular and intracellular compartments based on measurements made in two series of experiments. In one, tissue samples were collected and analysed for total water, Na+, K+ and Cl-. In the other, tissue extracellular volume fraction, [Na+] and [K+] were measured in situ using ion-selective microelectrodes. 3. Osmotically induced water loss from cerebral cortex was less than that predicted for ideal osmotic behaviour, revealing a degree of volume regulation, and this regulation was associated with net tissue uptake of Na+, Cl- and K+. 4. Total water content was 3.77 g H2O (g dry weight)-1 in control cortex and this decreased by 7% after 30 min of hypernatremia and then remained relatively stable at this value. Control extracellular water content, based on an extracellular volume fraction of 0.18, was 0.88 g H2O (g dry weight)-1. Control intracellular water content, estimated as the difference between total and extracellular water contents, was 2.89 g H2O (g dry weight)-1. After 30 min of hypernatremia, extracellular water content decreased by an average of 27% but intracellular water did not change. This indicates selective regulation of cell volume. By 90 min the extracellular water content had decreased by 47% and the loss in extracellular water content appeared to be accompanied by a roughly equivalent increase in intracellular water content. The intracellular volume increase, however, was not statistically significant. The tortuosity of the extracellular space averaged 1.57 and increased to 1.65 during the hypernatremia. 5. Brain extracellular fluid and plasma [Na+] were roughly equal in control tissue. Both increased by 30 mu equiv (g H2O)-1 as a result of the hypernatremia, although extracellular [Na+] lagged behind the plasma value during much of the first 60 min of hypernatremia. Extracellular [K+] was homeostatically regulated at 3 mu equiv (g H2O)-1 independent of changes in plasma electrolytes. 6. Estimates of extracellular and intracellular ion content (mu equiv (g dry weight)-1) indicate that extracellular Na+, Cl- and K+ content decreased during hypernatremia, by 32, 21 and 42% respectively, whereas intracellular ion content increased by 100, 169 and 5% respectively. 7. It is concluded that during acute hypernatremia the extracellular space decreases in volume through the loss of water and electrolytes while the intracellular compartment maintains its water content and gains electrolytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Diffusion characteristics and extracellular volume fraction during normoxia and hypoxia in slices of rat neostriatum.

1. Diffusion properties of submerged, superfused slices from the rat neostriatum were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA+) introduced by iontophoresis. TMA+ was sensed at an ion-selective microelectrode (ISM) positioned 100-150 microns from the source pipette. Slice viability was assessed from the extracellular field potentials evoked by intrastriatal electrical stimulation. 2. Under normoxic conditions the extracellular volume fraction (alpha) was 0.21 (range 0.18-0.24), and the tortuosity (lambda) was 1.54, in slices with good field potentials. In slices with poor field potentials, alpha was 0.09-0.16. Extraction of correct alpha and lambda in the slice required evaluation of nonspecific uptake, k', which was 1 x 10(-2) s-1. 3. Slices were made hypoxic by superfusing physiological saline equilibrated with 95% N2-5% CO2 for 10-30 min. Synaptic components of field potentials were inhibited after 3-4 min in hypoxic media. In some experiments extracellular K+ concentration [( K+]o) was monitored with ISMs. During hypoxia, [K+]o rose from an average baseline of 5.1 mM to 7-10 mM. After reoxygenation, [K+]o transiently fell below the original level. 4. The average value for alpha during hypoxia was 0.13 (a 38% decrease), which was significantly different from control (P less than 0.001) and increased progressively during hypoxic exposure. In contrast, tortuosity and k' were unchanged by this treatment. 5. These data represent the first characterization of the diffusion properties of the rat striatal slice and of changes in extracellular volume fraction during hypoxia in a brain slice preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

Multimodal characterization of population responses evoked by applied electric field in vitro: extracellular potential, magnetic evoked field, transmembrane potential, and current-source density analysis.

An external electric field applied parallel to longitudinal axis of neurons selectively depolarizes either end and thereby activates voltage-sensitive conductance changes in a large population of neurons. Here, we characterized such population responses in the in vitro turtle cerebellum. The responses were recorded and analyzed using a multimodal approach: the magnetic evoked field was measured using a Superconducting Quantum Interference Device (SQUID) magnetometer, and concurrently the electric field potentials were recorded. Laminar profile and current-source density analysis were used to uncover the pattern of activation due to the applied electric field. Intracellular recording provided further information for identifying the elements producing the observed responses. Finally, pharmacological manipulations confirmed the nature of the conductance changes. Our results show that it is possible to activate a defined cell population of the cerebellum by an applied field and obtain a magnetic response of the order of 0.5-2 pT. A field applied from the dorsal to the ventral side of cerebellum produced tetrodotoxin-sensitive population spikes. This component was followed by a kynurenic acid (KYNA)-sensitive postsynaptic response, most likely comprised of Ca(2+)-mediated action potentials occurring at the proximal pole of the Purkinje cell dendrites and evoked by climbing fiber inputs. The applied electric field directed from the ventral to the dorsal side of cerebellum gave rise to a complex of responses that was made up of a KYNA-sensitive component (presumably synaptically activated) and an Mn(2+)-sensitive but KYNA-insensitive component (probably due to a directly activated calcium conductance change). This study provides insights into the effects of electric and magnetic fields applied to the nervous tissue of experimental animal and human studies.

Animals↗
PubMed1990

Glutamate- and aspartate-induced extracellular potassium and calcium shifts and their relation to those of kainate, quisqualate and N-methyl-D-aspartate in the isolated turtle cerebellum.

Ion-selective microelectrodes can be used to evaluate the characteristics and laminar distribution of excitatory amino acid agonist-induced K+ and Ca2+ shifts in the extracellular environment of brain cells. This report describes the pattern of K+ increases and Ca2+ decreases elicited by glutamate and aspartate at 100 microns intervals in the isolated turtle cerebellum. These responses were compared to ion shifts evoked by kainate, quisqualate and N-methyl-D-aspartate. Glutamate and aspartate produced indistinguishable laminar patterns of ion shifts, with the greatest [K+]o and [Ca2+]o shifts in the granular layer. The average maximum granular and molecular layer increases in [K+]o were, respectively, 130% and 24% larger than the increase in the Purkinje cell layer. Kainate-induced increases in [K+]o also followed this granular greater than molecular greater than Purkinje cell layer pattern; however, the corresponding [Ca2+]o decreases were smaller and more variable. Quisqualate-evoked ion shifts in the molecular layer closely mimicked the shape of glutamate- and aspartate-induced responses. In the granular layer, however, quisqualate caused little ion change during iontophoresis followed by large [K+]o and [Ca+]o shifts after the end of the pulse. The minimal ion shifts induced during quisqualate application in the granular layer gave this agonist the distinction of being the only agent tested to have its greatest direct effect in the molecular layer. N-Methyl-D-aspartate caused large, two-phase [K+]o and [Ca2+]o shifts in the granular layer, only small [K+]o rises in the Purkinje cell and ventral molecular layers, and no response in the dorsal molecular layer. The lack of similarity between glutamate- and aspartate-induced ion shifts in the granular layer and those of any one agonist demonstrate the mixed agonist action of glutamate and aspartate in the cerebellum. These studies provide new information about the dynamics of excitatory amino acid receptor activation that is complementary to autoradiographic receptor mapping data and to single cell electrophysiological studies.

Amino Acids↗
PubMed1990

Distortion of magnetic evoked fields and surface potentials by conductivity differences at boundaries in brain tissue.

We investigated the conditions under which inhomogeneity in electrical conductivity may significantly modify the magnetic evoked field (MEF) due to primary currents (i.e., neuronal currents) in the brain. In the case of an isolated turtle cerebellum immersed in a large bath of physiological saline, our theoretical analysis showed the cerebellar surface to significantly enhance the MEF due to a primary current, by a factor of as much as two, for experimentally determined values of the conductivities of the cerebellar tissue and saline. A further parametric investigation of the conductivity effect revealed that conductivity boundaries may significantly modify the MEF due to neuronal currents located within 1 mm of a conductivity boundary, as would be the case for active neurons near an edema, an anoxic fringe such as might occur during stroke, or a ventricle in the human head. For a stationary neural source, conductivity boundaries may modify the magnitude of its MEF without affecting its temporal waveform. However, this boundary effect was found to be small for a model geometry locally approximating cortical sources in a sulcus or a fissure, where the boundary effects from adjacent sulcal walls tend to cancel each other.

Animals↗
PubMed1989

Measurement of nanomolar dopamine diffusion using low-noise perfluorinated ionomer coated carbon fiber microelectrodes and high-speed cyclic voltammetry.

Several improvements in the fabrication and use of carbon fiber voltammetric microelectrodes (CFVMs) are described. These procedures did not involve oxidative treatment, but resulted in sensitivities and selectivities approaching those of treated CFVMs, without the inherent slow response times associated with the latter electrodes. To accomplish this we reduced CFVM noise by (1) improving the adhesive seal between the 8 microns o.d. carbon fiber and the glass insulation using vacuum, (2) snapping rather than cutting or beveling the fiber to be flush with the glass, and (3) using a concentrated electrolyte solution to make electrical contact with the fiber. System noise was reduced by digital smoothing and signal averaging. Selectivity of the CFVMs for dopamine over ascorbate was enhanced to better than 2000:1 by coating with Naflon, a perfluorinated cation exchange polymer, using a low (+0.5 V vs Ag/AgCl) electroplating potential. This low voltage also prevented electrode surface oxidation. To demonstrate the performance of our CFVMs, we used them in conjunction with high-speed cyclic voltammetry to accurately measure the diffusion coefficient of iontophoretically released dopamine at concentrations as low as 35 nM over distances of less than 200 microns in agarose gel.

Diffusion↗
PubMed1989

Changes in dietary patterns over a 6-year period in an elderly population.

We have not employed a rigid statistical interpretation of the data in this report because, as Botwinick and Arenberg pointed out, the time span of a study (if short enough) and the number of independent observations (if small enough) can affect statistical significance. In the present study, the time span was only 6 years, and the males, as well as the females, were grouped into a single age cohort. These limitations do not allow us to assess true time effects. Nevertheless, we attributed the differences noted between the cross-sectional and longitudinal slopes to a time effect, that is, to a secular trend, over the span of the study. This conclusion was based on the following line of reasoning: First, we assumed that there were no significant cohort effects in the population considered in the present study. This assumption was supported by results from the Baltimore Longitudinal Study of Aging, where no cohort effects were found. (In the Baltimore study, 180 males were followed over a period of 15 years, and the age range covered 40 years.) Second, we documented evidence that the participants in the present study actively limited their cholesterol and fat intake because of their keen awareness of an association between cholesterol intake and coronary heart disease as reported in the lay press over the past 10 years. In the healthy male population considered in the present study, we determined that there was a decrease in daily energy intake of approximately 12 kcal/year. We based this determination on the average of the cross-sectional analysis as we attributed much of the negative effect noted in the longitudinal analysis, as stated above, to a secular trend. Aging had a much lower negative effect on energy intake in the female population, being approximately 4 kcal/year. The decrease in protein intake with age was higher in males (1.1 g/day/year) than in females (0.6 g/day/year). This finding parallels the large negative effect of aging in energy intake noted for males compared with females. The same sex difference was noted for carbohydrate intake between males and females (-0.4 and -0.2 g/day/year, respectively). The cross-sectional findings for fat intake are unremarkable for the males (no change) as well as for the females (only -0.1 g/day/year).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Avoiding the pitfalls of epidural anesthesia in obstetrics.

The benefits of epidural anesthesia for the relief of pain associated with childbirth has long been recognized. Although epidurals are widely used for pain relief during the labor process, side effects and complications associated with epidurals do occur. The purpose of this review is to summarize the benefits, as well as the disadvantages of epidurals, in an effort to minimize those complications.

Anesthesia, Epidural↗
PubMed1988

Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum.

This study evaluated the role of excitatory amino acid (EAA) receptor activation in spreading depression (SD), using the in vitro turtle cerebellum as a model system. SD was triggered by electrical stimulation or by elevated K+ after the cerebellum had been conditioned for at least 30 min with physiological saline in which most of the chloride had been replaced by propionate. SD was recognized as a transient (1-3 min) negative shift of extracellular potential accompanied by depression of evoked potentials (15-30 min) and an increase of extracellular K+ up to 60 mM, which spread across the cerebellum at rates of 1-7 mm/min. SD usually commenced in the granular layer, which apparently contains the 3 major EAA receptor subtypes, quisqualate, kainate and N-methyl-D-aspartate (NMDA), then subsequently spread to the molecular layer, which is largely free of NMDA receptors. Glutamate, aspartate, NMDA, kainate and quisqualate all triggered SD. Kynurenic acid and 2-aminophosphonovaleric acid (APV) inhibited SD under certain conditions further suggesting involvement of EAA receptors. The initiation of SD was blocked by high Mg2+ and facilitated in low extracellular Mg2+, which also eliminated the delay in molecular layer SD onset. Our data suggest that no one EAA receptor subtype is singly responsible for SD.

2-Amino-5-phosphonovalerate↗
PubMed1985

Organization of the filum terminale in the frog.

The histological organization of the filum terminale of the spinal cord in Rana catesbeiana and Rana pipiens was characterized to determine if this region possessed an organized neuropil or whether it was merely a glial remnant that persisted after absorption of the larval tail. The excised filum was maintained in vitro. Intracellular electrophysiological recording was performed with horseradish peroxidase injection. Tyrosine hydroxylase and serotonin distribution were revealed by immunocytochemical methods. Astroglia were the dominant cell type and displayed an elaborate variety of forms. The mean membrane potential was logarithmically related to the extracellular potassium concentration but displayed a sub-Nernstian slope. Oligodendroglia were also seen, as well as ependyma that extended from the central canal to the pial surface. Neuronal activity was revealed by occasional intracellular penetration of elements that displayed spontaneous excitatory postsynaptic or action potentials. The major evidence for the presence of neurons was the demonstration of tyrosine hydroxylase (TH) immunoreactivity in a large population of cerebrospinal fluid-contacting neurons that abutted the ventral half of the central canal. The axons of these cells entered a ventral bundle and ascended the cord; some fibers left this tract and apparently terminated on large arcuate neurons within the filum. Serotoninergic fibers were primarily confined to a subpial location at the dorsal midline. We conclude that the filum terminale of the frog has a sparse but functional neuropil that is organized around the central canal and supported by a profusion of elaborate glial forms.

Animals↗