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Biomedical subjects

J L Taylor

Publications and source records attributed to J L Taylor.

At least 55 records · Page 3Linked to original sources
PubMed2000

Ethanol pharmacokinetics in white women: nonlinear model fitting versus zero-order elimination analyses.

BACKGROUND: Studies have shown repeatedly that ethanol pharmacokinetics are not linear, yet most researchers still determine ethanol elimination by linear, zero-order kinetics. The goals of the present work were to: (1) fit four nonlinear pharmacokinetic models to mean breath alcohol concentration (BrAC)-time data of 27 women and determine the best-fit model; (2) fit the determined best-fit model to individual BrAC data and estimate the pharmacokinetic parameters; and (3) compare the method of nonlinear model fitting with the classical zero-order elimination method and determine in which cases the classical approach is justified. METHODS: Twenty-seven healthy white women ingested four drinks (total of 0.67 g x kg(-1)) of ethanol on two test days. Approximately 24 breath ethanol samples (for pharmacokinetic analyses) and one blood sample (for hormonal markers) were taken per day. Pharmacokinetic model evaluation was based on the coefficient of variation, the weighted residual sum of squares, and the sequence of the weighted residuals. Because hormonal changes across the menstrual cycle did not significantly influence ethanol pharmacokinetics, data from the two test days were pooled. RESULTS: The best-fit model was a one-compartment open model with first-order absorption and sequential first-order elimination, followed by Michaelis-Menten elimination kinetics. Fitting this model to the individual BrAC data yielded mean ka = 0.062 hr(-1), Vd = 0.457 L x kg(-1), ke = 0.011 hr(-1), Vmax = 0.136 g x L(-1) x hr(-1), and Km = 0.096 g x L(-1). For the classical analyses, mean time to peak BrAC = 1.83 hr, disappearance rate = 0.179 g x L(-1) x hr(-1), and area under the blood ethanol-time curve (AUC) = 2.884 g x L(-1) x hr. Correlational analyses showed that more frequent drinkers eliminated ethanol significantly faster and reached significantly lower AUC than less frequent drinkers. CONCLUSIONS: After multiple dose ingestion in white women, classical zero-order elimination analyses can be applied only to a limited portion of the descending BrAC-time curve. They seem justified and practical from 0.5 hr after peak BrAC until BrAC reaches 0.2 g x L(-1). To describe ethanol pharmacokinetics across the entire BrAC-time curve, however, sophisticated nonlinear model fitting is required.

Adult↗
PubMed1999

Impaired response of human motoneurones to corticospinal stimulation after voluntary exercise.

1. Activation of descending corticospinal tracts with transmastoid electrical stimuli has been used to assess changes in the behaviour of motoneurones after voluntary contractions. Stimuli were delivered before and after maximal voluntary isometric contractions (MVCs) of the elbow flexor muscles. 2. Following a sustained MVC of the elbow flexors lasting 5-120 s there was an immediate reduction of the response to transmastoid stimulation to about half of the control value. The response recovered to control levels after about 2 min. This was evident even when the size of the responses was adjusted to accommodate changes in the maximal muscle action potential (assessed with supramaximal stimuli at the brachial plexus). 3. To determine whether the post-contraction depression required activity in descending motor paths, motoneurones were activated by supramaximal tetanic stimulation of the musculocutaneous nerve for 10 s. This did not depress the response to transmastoid stimulation. 4. Following a sustained MVC of 120 s duration, the response to transcranial magnetic stimulation of the motor cortex gradually declined to a minimal level by about 2 min and remained depressed for more than 10 min. 5. Additional studies were performed to check that the activation of descending tracts by transmastoid stimulation was likely to involve excitation of direct corticospinal paths. When magnetic cortical stimuli and transmastoid stimuli were timed appropriately, the response to magnetic cortical stimulation could be largely occluded. 6. This study describes a novel depression of effectiveness of corticospinal actions on human motoneurones. This depression may involve the corticomotoneuronal synapse.

Adult↗
PubMed1999

Effects of galvanic vestibular stimulation during human walking.

1. To identify vestibular influences on human walking, galvanic vestibular stimulation was applied to normal adult subjects as they walked to a previously seen target. A transmastoidal step stimulus commenced as subjects started walking. With the eyes shut, the galvanic stimulus caused large turns towards the side with the anodal current. 2. Ability to perceive the trajectory of gait without visual cues was measured by guiding blindfolded subjects from one arbitrary point to another, either walking or seated in a wheelchair. On reaching a destination position and removing the blindfold, subjects pointed to indicate the starting position. Subjects made considerable errors in estimating the trajectory, but were equally accurate whether in the wheelchair or walking. 3. To determine the effects of vestibular stimulation on the perception of trajectory, the galvanic stimulus was applied to blindfolded subjects as they were guided from one point to another in the wheelchair. The vestibular stimulus produced an illusory shift in the trajectory travelled. This shift was towards the side with the cathode, i.e. in the opposite direction to the turn produced by the stimulus during walking. 4. We conclude that galvanic vestibular stimulation during walking causes subjects to turn from their planned trajectory. In part, this altered course may compensate for an altered perception of trajectory produced by the stimulus. However, altered perception of the vertical or the base of support, or direct vestibulo-fugal influences on the leg muscles could contribute to the changes in gait.

Adult↗
PubMed1999

Altered responses of human elbow flexors to peripheral-nerve and cortical stimulation during a sustained maximal voluntary contraction.

The short-latency electromyographic response evoked by transcranial magnetic stimulation (MEP) increases in size during fatigue, but the mechanisms are unclear. Because large changes occur in the muscle action potential, we tested whether changes in the response to stimulation of the peripheral motor nerve could fully account for the increase in the MEP. Subjects (n=8) performed sustained maximal voluntary contractions (MVCs) of the right elbow flexors for 2 min. During the contraction, the MEP and the response to supramaximal stimulation of motor-nerve fibres in the brachial plexus were alternately recorded. During the contraction, responses to motor-nerve stimulation increased in area by 87+/-35% (mean+/-SD) in the biceps brachii and 74+/-30% in the brachioradialis, but the area of the MEPs increased by 153+/-86% and 175+/-122%, respectively. Thus, the increase in the MEP was greater than the increase in the peripheral M-wave. The onset latency of the MEP in the biceps brachii increased by 0.7+/-0.6 ms (range: -0.2 to 1.9 ms) during the sustained contraction. A smaller increase occurred in response to peripheral nerve stimulation (0.3+/-0.3 ms; from -0.3 to 0.9 ms). In the contralateral elbow flexors, neither responses to transcranial magnetic stimulation nor responses to motor-nerve stimulation changed in size or latency. During the sustained contraction, the short silent period after stimulation of the peripheral nerve (48+/-5 ms in biceps brachii and 48+/-4 ms in brachioradialis) increased in duration by about 12 ms (to 61+/-12 ms and 60+/-9 ms, respectively), whereas the silent period following transcranial magnetic stimulation increased from 238+/-39 ms in biceps brachii and 243+/-34 ms in brachioradialis to 325+/-41 ms and 343+/-42 ms, respectively. During a sustained MVC, while the motor responses to peripheral and to cortical stimulation grow concurrently, growth of the MEP cannot be entirely accounted for by changes in the muscle action potential. Hence, some of the increase in MEP size during fatigue must reflect changes in the central nervous system. Increased latency of the MEPs and lengthening of the peripherally evoked silent period are consistent with decreased excitability of the alpha motoneurone pool. Thus, an increased response from the motor cortex to the magnetic stimulus remains a likely contributor to the increase in the size of the MEP in fatigue.

Adult↗
PubMed1999

Synergistic anti-varicella-zoster virus activity of interferon-alpha 2a and acyclovir in corneal cells.

Human corneal stromal (HCS) cells in cultures established from donor corneas can serve as host cells for replication of varicella-zoster virus (VZV). Comparative infectious centers assays suggest that HCS cells are more restrictive hosts than MRC-5 cells, a line of human embryonic lung fibroblasts, commonly used for VZV isolation. VZV propagated in MRC-5 cells was infectious for both MRC-5 and HCS cells, but titers in HCS were one fifth of those in MRC-5 cells. Inhibition of VZV replication in HCS cells by acyclovir (ACV), recombinant human interferon-alpha 2a (IFN-alpha 2a), or the combination of these two antivirals was detected by both an infectious centers-plaque-reduction assay and an ELISA method using monoclonal anti-VZV antibody. In the infectious centers-plaque-reduction assay combinations of ACV with IFN-alpha 2a showed synergistic anti-VZV activity. VZV protein synthesis, as detected by the ELISA, was a less sensitive measure of the antiviral effects producing an ED50 value of 50 microM for ACV, five to ten times the ED50 determined in the plaque reduction assay. In the ELISA, high titers of IFN-alpha 2a (2000 IU/ml) decreased virus antigen expression only slightly, while combinations of ACV and IFN-alpha 2a were synergistic in their detected anti-VZV activity. These data document the replication of VZV in HCS cells and demonstrate that VZV is sensitive to the synergistic antiviral action of combinations of IFN-alpha 2a and ACV.

Acyclovir↗
PubMed1999

Assessing depressive symptoms in multiple sclerosis: is it necessary to omit items from the original Beck Depression Inventory?

Overlap between depression scale item content and medical symptoms may exaggerate depression estimates for patients with multiple sclerosis (MS). We reconsider Mohr and co-workers' (1997) recommendation to omit Beck Depression Inventory (BDI) items assessing work ability (item 15), fatigue (17), and health concerns (20) for MS patients. Subjects were medical patients with either MS (n = 105) or a medical disorder for which the BDI is empirically supported [diabetes mellitus (DM), n = 71; chronic pain (CP), n = 80], psychiatric patients with depressive disorder (MDD; n = 37), and healthy controls (HC; n = 80). Relative scores for the eight "somatic" BDI items were analyzed by multivariate analysis of variance with demographic variables and BDI total as covariates. The only significant difference was MS > HC (item 15). On raw scores, MS patients exceeded HCs on items 15 and 21 (sexual disinterest), but this was attributable to the low HC item endorsement. There were no other differences on somatic items or item-total correlations. Scale consistency was good across groups, regardless of item omission. Somatic items were unassociated with major MS parameters. We thus encourage continued application of the full BDI for assessing depressive symptoms in patients with MS.

Adult↗
PubMed1999

Relationship of age and simulated flight performance.

OBJECTIVE: To determine the relationship between age and aviator performance on a flight simulator. DESIGN: A cross-sectional observational study. PARTICIPANTS: The sample consisted of 100 aviators aged 50 to 69 (mean = 58). MAIN OUTCOME MEASURES: Pilots were tested on a Frasca 141 flight simulator (Urbana, IL), linked to a UNIX-based IRIS 4D computer (Silicon Graphics, Mountain View, CA), which both generated graphics of the environment in which the pilots flew and collected data concerning the aircraft's flight conditions. RESULTS: We found that increased age was significantly associated with decreased aviator performance on a flight simulator. CONCLUSIONS: Although there was a significant relationship between increased age and decreased aviator performance, age explained 22% or less of the variance of performance on different flight tasks; hence, other factors are also important in explaining the performance of older pilots.

Aerospace Medicine↗
PubMed1999

Effects of menstrual cycle and female sex steroids on ethanol pharmacokinetics.

This study investigated the influence of menstrual cycle and female sex steroid levels on ethanol pharmacokinetics. In a within-subjects design, 24 female volunteers each consumed 0.67 g x kg(-1) ethanol during the menstrual and luteal phases of their menstrual cycle. On each test day, we collected blood samples before ethanol administration to determine estradiol (E2) and progesterone (P) levels and to confirm ovulation. We took 20 or more postdrink breath ethanol concentration readings and examined pharmacokinetic differences between the two phases, using classical pharmacokinetic measures, as well as Michaelis-Menten measures. Despite highly significant differences in measured E2 as well as P levels on the 2 test days, and despite excluding subjects with anovulatory cycles from the analysis, there were no significant differences between menstrual and luteal phases for any of the pharmacokinetic variables. We found no correlation between E2 or P levels and any of the pharmacokinetic measures. In summary, we found no evidence that the tested menstrual cycle phases or varying E2 and progesterone levels significantly influence ethanol pharmacokinetics. Because previous studies about the topic have used few subjects and revealed controversial results, we consider our negative findings based on 24 subjects meaningful.

Adult↗
PubMed1999

Gender differences in moderate drinking effects.

Women appear to become more impaired than men after drinking equivalent amounts of alcohol, achieving higher blood alcohol concentrations even when doses are adjusted for body weight. This finding may be attributable in part to gender differences in total body water content. Men and women appear to eliminate approximately the same total amount of alcohol per unit body weight per hour. However, women seem to eliminate significantly more alcohol per unit of lean body mass per hour than men. Some studies report that women are more susceptible than men to alcohol-related impairment of cognitive performance, especially in tasks involving delayed memory or divided attention functions. Psychomotor performance impairment, however, does not appear to be affected by gender. This article provides an overview of alcohol metabolism (pharmacokinetics) and reviews recent studies on gender differences in alcohol absorption, distribution, elimination, and impairment. Speculation that gender differences in alcohol pharmacokinetics or alcohol-induced performance impairment may be caused by the menstrual cycle and variations in female sex hormones are discussed. It is concluded that the menstrual cycle is unlikely to influence alcohol pharmacokinetics.

Alcohol Drinking↗
PubMed1998

Movement detection at the human big toe.

1. To be detected, movements of the interphalangeal joint of the big toe must be greater than at other joints. This poor acuity may arise because the anatomy of the foot and ankle results in poor coupling between the toe and the muscles that operate it. To vary this coupling, the effect of ankle position on proprioceptive acuity at the toe was measured. 2. We measured proprioceptive acuity at the toe with the ankle in different positions and found that ankle plantarflexion did improve acuity. This implies that, with the ankle at mid-range or dorsiflexed, toe movement is inadequately transferred to muscle fascicles. 3. To determine actual changes in fascicle length of the toe extensor, movements of extensor hallucis longus near the toe and at the muscle-tendon junction were measured during surgical exposure in one subject. Ankle position greatly affected movement transfer from toe to muscle-tendon junction: no tendon movement was transferred with the ankle dorsiflexed, but all movement was transferred with the ankle plantarflexed. 4. When the relationship between joint rotation and muscle fascicle length measured in vivo was used to express the smallest detectable movements of the toe as proportional changes in muscle fascicle length, these detectable changes were similar to those at all other limb joints. This suggests that change in muscle fascicle length is of major interest to the nervous system.

Adult↗
PubMed1998

Absence of viscerosomatic inhibition with injections of lobeline designed to activate human pulmonary C fibres.

1. Activation of pulmonary C fibres (J receptors) in animals produces inhibition of spinal motoneurones. Intravenous bolus injections of lobeline are believed to activate pulmonary C fibres (J receptors) in human subjects and to produce characteristic sensations and cardiorespiratory responses. This study quantified the respiratory sensations evoked by such injections and then used a range of suprathreshold doses of lobeline and tested for the presence of reflex or descending inhibition of motoneuronal output. 2. Injections of lobeline produced dose-dependent sensations of respiratory discomfort referred to the throat and upper chest beginning within about 10 s and often associated with coughing. As the dose increased the latency for the sensations decreased while their duration and intensity increased. Reflex changes in blood pressure, heart rate and ventilation also occurred. 3. Injections of lobeline at doses sufficient to evoke respiratory discomfort lasting 25-32 s (37-73 microgram kg-1) increased the size of the H reflex in soleus with an onset latency of about 10 s and lasting about 20 s. 4. The size of EMG responses evoked in upper limb muscles by transcranial magnetic stimulation of the motor cortex increased shortly after injections and remained elevated for about 30-35 s. 5. Injections of lobeline during sustained voluntary contractions of the elbow flexors at submaximal or maximal levels did not impair the ability to produce force. 6. Walking was not disrupted by repeated suprathreshold doses of lobeline. 7. It is concluded that injections of lobeline sufficient to evoke cardiorespiratory reflexes and sensations of severe respiratory discomfort are not associated with functionally important inhibition of motor performance. The results cast doubt on the ability of the J reflex to limit exercise in humans.

Adult↗
PubMed1998

Inhibition of muscle sympathetic outflow following transcranial cortical stimulation.

The possible contribution of cerebral cortical activity to sympathetic outflow to the muscle vascular bed was assessed in normal human subjects. Muscle sympathetic activity was recorded from motor fascicles of the peroneal nerve in 8 subjects while transcranial magnetic stimulation was applied over the vertex, or unilaterally over the hand area of cortex. By triggering the cortical stimulus from the R-wave of the ECG and introducing delays of 0-600 ms between the trigger and the stimulus, we found that a single cortical stimulus delayed by 200-400 ms caused a pronounced inhibition of one pulse-synchronous sympathetic burst. Stimulation over the vertex was more effective than stimulation over the hand area of cortex. In addition to this inhibition of muscle sympathetic outflow, brain stimulation caused an increase in cutaneous sympathetic activity, both sudomotor (sweating) and vasoconstrictor (decrease in skin blood flow). We suggest that the cerebral cortex may normally suppress muscle sympathetic outflow and speculate that lesions that interrupt this source of inhibition (such as those caused by stroke) may result in an augmented muscle sympathetic outflow.

Adult↗
PubMed1998

Influence of nicotine on simulator flight performance in non-smokers.

In a placebo-controlled study, we investigated the influence of nicotine on late-day aviation performance in 15 non-smoking subjects. In a within-subjects design, subjects were tested on 2 days, each lasting 8 h and consisting of three 75-min simulator flights (late-afternoon practice, evening test, night test). Prior to each test, subjects received either nicotine polacrilex 2 mg or placebo gum. As expected, overall performance was significantly better after nicotine, compared to placebo (P < 0.01). Post-hoc analysis of individual flight tasks showed that nicotine improved scores on approach to landing, a task which appears to require sustained attention. We conclude that nicotine may improve late-day flight performance in non-smoking aviators.

Adult↗
PubMed1998

Combined effects of interferon-alpha and acyclovir on herpes simplex virus type 1 DNA polymerase and alkaline DNase.

Treatment of cells with combinations of human interferon-alpha (IFN-alpha) and the nucleoside analog, acyclovir (ACV), leads to the synergistic inhibition of herpes simplex virus type 1 (HSV-1) replication. We have examined the effect of these agents on the replication of HSV-1 DNA and the synthesis of early viral enzymes to understand the mechanism(s) responsible for this synergistic activity. Combination treatment with 100 IU/ml IFN-alpha and 5 microM ACV led to HSV-1 DNA levels more than 8-fold lower than in cells treated with ACV alone, while IFN-alpha treatment alone had no detectable effect on viral DNA synthesis. Steady state levels of DNA polymerase were reduced approximately 50% by IFN-alpha and 25% by ACV, but combination treatment did not decrease enzyme levels to an extent greater than the sum of these effects. In contrast, the activity of another early viral enzyme, alkaline DNase, was reduced less than 20% by IFN-alpha alone or combination treatment and was unaffected by ACV treatment. No decrease in the level of mRNA encoding either enzyme was detected in IFN-alpha-treated cells although ACV treatment reduced polymerase mRNA levels. These studies suggest that the synergistic anti-HSV activities of IFN-alpha with ACV could be mediated, in part, through some post-transcriptional mechanism induced by IFN-alpha treatment, leading to the reduction in production of viral early enzymes, especially DNA polymerase.

Acyclovir↗
PubMed1998

The effects of interferon-alpha and acyclovir on herpes simplex virus type-1 ribonucleotide reductase.

Herpes simplex virus-type 1 (HSV-1) encodes both the small (UL40) and large (UL39) subunits of the enzyme, ribonucleotide reductase. Treatment of HSV-1-infected cells with interferon-alpha (IFN-alpha) reduced the levels of both enzyme subunits. Reduced steady state levels of the large subunit were demonstrated by immunoblot using polyclonal antibody specific for the viral enzyme. Reduction in the amount of small subunit was shown by a reduction in the electron spin resonance signal derived from the iron-containing tyrosyl free-radical present in this subunit. Treatment of cells with 100 IU/ml of IFN-alpha decreased levels of both subunits resulting in a reduction in enzyme activity as measured by conversion of CDP to dCDP. The decrease in the amount of the large subunit was not due to a reduction in the level of its mRNA. The combination of IFN-alpha and ACV treatment of human cornea stromal cells did not result in a further reduction in amounts of ribonucleotide reductase relative to that detected with IFN-alpha alone. The IFN-alpha-induced reduction in ribonucleotide reductase activity is the likely cause of decreased levels of dGTP which we have previously demonstrated in IFN-alpha-treated, infected cells.

Acyclovir↗
PubMed1998

Reduced excitability of the cortico-spinal system during the warning period of a reaction time task.

Seven subjects made a wrist flexion movement as rapidly as possible in response to a cutaneous shock on the opposite hand. In some trials, an auditory warning signal was given 0.5 s beforehand. In random trials, transcranial magnetic stimulation (TMS) was used to elicit EMG responses (MEPs) in forearm flexor and extensor muscles 0-500 ms before the cutaneous shock. H-reflexes were elicited in flexor muscles at the same intervals. The warning stimulus reduced reaction time from about 400 ms to 200 ms. MEPs in the flexor muscles were significantly suppressed from 125 ms after the warning stimulus until the time of the cutaneous shock whilst MEPs in the extensors, and H-reflexes in the flexor were either unaffected, or reduced by a smaller amount at a later time. Responses in relaxed contralateral muscles were unchanged. If the task was changed to a choice reaction, in which the imperative stimulus (but not the warning signal) indicated whether to flex or extend the wrist, then there was no change in the MEPs or H-reflex in the warning period. A similar effect was seen if the duration of the warning period was extended from 0.5 to 2 s in a simple reaction (flexion) task. We conclude that increased excitability of the corticospinal output is not required to speed up reaction times. The time taken to discharge cortical output elements is relatively unimportant compared with the time needed to process the sensory input and link it to the motor output.

Adult↗