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Biomedical subjects

J A Bennett

Publications and source records attributed to J A Bennett.

At least 37 records · Page 2Linked to original sources
PubMed1999

Time dependence of anodal and cathodal refractory periods in cardiac tissue.

Mehra et al. (PACE 1980; 3:526) observed that immediately after implantation of a pacing electrode in a dog heart, the anodal refractory period (RP) is shorter than the cathodal RP, but after several weeks the anodal RP becomes longer than the cathodal RP. We examine this experiment using numerical simulations based on the bidomain model of cardiac tissue and a Beeler-Reuter membrane. Our hypothesis is that accumulation of inexcitable tissue around the electrode following implantation causes the effective size of the electrode to increase and that this increase is the mechanism underlying the change in RP. We calculate that the anodal RP is shorter than the cathodal RP for both large and small electrodes. However, for large electrodes the threshold for anode "break" stimulation is greater than 8 mA. Mehra et al. defined RP experimentally as the interval at which the threshold stimulus strength becomes greater than 8 mA. If we restrict the stimulus current in our calculations to less than 8 mA, we exclude anode break stimulation from our calculation of the RP. In that case, our results are consistent with Mehra et al. and suggest that their observation resulted from their definition of RP.

Animals↗
PubMed1999

The contribution of the swallowed fraction of an inhaled dose of salmeterol to it systemic effects.

Salmeterol is approximately eight times as potent as salbutamol for systemic effects. This may be because the drug is eight times more potent on receptors or there may be differences in systemic bioavailability. The systemic effects of salbutamol are limited by its fairly high first-pass metabolism, but the oral bioavailability of salmeterol is unknown. The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic effects were analysed in a randomized, double-blind, crossover study. Twelve healthy subjects were given inhaled salmeterol 400 microg, inhaled salmeterol 400 microg plus oral activated charcoal or inhaled placebo plus oral activated charcoal on three separate days. Cardiac frequency (fC), Q-T interval corrected for heart rate (QTc), plasma potassium and glucose concentrations were measured for 4 h following the inhaled drug. Salmeterol with and without oral charcoal produced significant changes for all measures compared to placebo. The magnitude of effect following salmeterol alone was significantly greater than that following salmeterol plus charcoal for fC and glucose (mean (95% confidence interval) differences 8 (2-13) beats x min(-1), 0.59 (0.04, 1.13) mmol x L(-1), respectively) and nonsignificantly greater for QTc interval and potassium concentration. The differences between salmeterol given with and without charcoal suggest that 28-36% of the systemic response to salmeterol administered from a metered-dose inhaler are due to drug absorbed from the gastrointestinal tract. Thus, most of the systemic effects are due to the inhaled fraction of the drug.

Administration, Inhalation↗
PubMed1999

Activities of daily living. Old-fashioned or still useful?

1 The Index of Activities of Daily Living (ADL) is used by many nurses to assess function in older adults, but there is debate regarding the scoring, wording of questions, and validity in diverse populations. 2 Older adults may give inaccurate answers to ADL questions because they misunderstand the questions, have personal reasons for underreporting or overreporting difficulty in ADL, or fail to recognize difficulty because they have adapted to changes in function. 3 Physical performance tests, especially of the lower extremities, may be an alternative method of assessing function, especially in high-functioning older adults who report no difficulty in ADL.

Activities of Daily Living↗
PubMed1998

Noise-induced threshold shift dynamics measured with distortion-product otoacoustic emissions and auditory evoked potentials in chinchillas with inner hair cell deficient cochleas.

Chinchillas (n = 6) were treated with carboplatin and, following a 30-day recovery period, were exposed to a 115 dB peak SPL impact noise presented at a rate of l/s for 6 h/day for 10 days. A second group (n = 6) received only the noise treatment. Cubic distortion product otoacoustic emissions (2f1-f2) and auditory evoked potential (AEP) detection thresholds in response to tone bursts were measured before and 30 days after drug treatment and following the first and 10th day of the noise exposure. Thirty days after the final exposure day, permanent changes in AEP detection thresholds and emissions were measured and cochleograms constructed. The drug treatment eliminated over 80% of the inner hair cells (IHC) in the cochlea, leaving the outer hair cell (OHC) population essentially intact prior to the interrupted noise exposure. The drug treatment alone had very little or no effect on AEP detection thresholds and emission metrics. Following the noise exposure, the IHC-deficient animals showed clear 'toughening' effects in the AEP and emission measures which were the same as measured in the group receiving only the noise. After a 30-day post-exposure recovery period. AEP thresholds were elevated about 10 dB at the low frequencies in the drug-noise group whereas emissions returned to near normal despite the massive IHC losses. These results are consistent with the idea that an intact OHC population is required for toughening. However, sound-evoked efferent pathways activated by the few remaining IHCs (approximately 20%) which, in this preparation, are distributed throughout the cochlea, may still contribute significantly to the toughening phenomena.

Animals↗
PubMed1998

The airway effects of stopping regular oral theophylline in patients with asthma.

AIMS: We investigated whether the deterioration in asthma control reported following cessation of theophylline was due to tolerance to theophylline. METHODS: Eighteen subjects with mild stable asthma were given oral theophylline 10 mg kg(-1) day(-1) or placebo for 2 weeks in a double-blind crossover study. FEV1 and PD20 histamine were measured before and 8 h after the first dose of treatment and 8, 32 and 56 h after the final dose. PD20 AMP was measured before treatment and 9 h after the final dose. RESULTS: Six patients did not tolerate theophylline. In the other 12 subjects there were no differences between treatments in daily PEF, symptom scores, rescue bronchodilator use, PD20 histamine or FEV1 up to 8 h post treatment. Following withdrawal of theophylline there were significantly lower values for mean FEV1 (mean difference 0.151, 95% CI 0.03, 026) and PD20 AMP compared to placebo but no difference in other end points. CONCLUSIONS: The small rebound deterioration in lung function following regular treatment with therapeutic doses of oral theophylline is consistent with the development of tolerance.

Administration, Oral↗
PubMed1998

A risk-benefit assessment of pharmacological treatments for panic disorder.

Panic disorder, a psychiatric disorder characterised by frequent panic attacks, is the most common anxiety disorder, affecting 2 to 6% of the general population. No one line of treatment has been found to be superior, making a risk-benefit assessment of the treatments available useful for treating patients. Choice of treatment depends on a number of issues, including the adverse effect profile, efficacy and the presence of concomitant syndromes. Tricyclic antidepressants (TCAs) are beneficial in the treatment of panic disorder. They have a proven efficacy, are affordable and are conveniently administered. Adverse effects, including jitteriness syndrome, bodyweight gain, anticholinergic effects and orthostatic hypotension are commonly associated with TCAs, but can be managed successfully. Selective serotonin (5-hydroxytryptamine; 5HT) reuptake inhibitors are also potential first line agents and are well tolerated and effective, with a favourable adverse effects profile. There is little risk in overdose or of anticholinergic effects. Adverse effects include sedation, dyspepsia and headache early in treatment, and sexual dysfunction and increased anxiety, but these can be effectively managed with proper dosage escalation and management. Benzodiazepines are an effective treatment, providing short-term relief of panic-related symptoms. Patients respond to treatment quickly, providing rapid relief of symptoms. Adverse effects include ataxia and drowsiness, and cognitive and psycho-motor impairment. There are reservations over their first-line use because of concerns regarding abuse and dependence. Monoamine oxidase inhibitors, because of their adverse effects profile, potential drug interactions, dietary restrictions, gradual onset of effect and overdose risk, are not considered to be first-line agents. They are effective however, and should be considered for patients with refractory disease. Valproic acid (valproate sodium), while not intensively studied, shows potential for use in panic disorder. More studies are needed in this area before the available data can be confirmed. As a supplement to drug therapy, cognitive behavioural therapy is effective. It is well tolerated, and may be beneficial in certain clinical situations. Its main drawback is the time commitment and effort needed to be made by the patient.

Antidepressive Agents, Tricyclic↗
PubMed1998

Alpha-fetoprotein derived from a human hepatoma prevents growth of estrogen-dependent human breast cancer xenografts.

Alpha-fetoprotein (AFP) is a transport protein that has growth-regulatory properties in many different tissues. It is known to interfere with responses stimulated by estrogen. The purpose of this study was to determine whether human AFP would inhibit the growth of human breast cancer. AFP was isolated from the culture supernatant of human hepatoma cells (HepG2) grown in serum-free medium and was purified by immunoaffinity chromatography. Human breast cancers were grown as xenografts under the kidney capsule of severe combined immunodeficient mice. The minimum inhibitory dose of AFP against estradiol (E2)-stimulated growth of human MCF-7 breast cancer xenografts was 10 microg/mouse/day, and maximum inhibition (no growth) was achieved with 100 microg/mouse/day. Daily treatment was required to sustain inhibition. This 100-microg dose of AFP also inhibited xenograft growth of E2-dependent T47 human breast carcinoma. Estrogen receptor-negative MDA MB 231 and BT20 human breast carcinoma xenografts were not inhibited by AFP (100 microg/mouse/day). Elevation in serum E2 occurred during AFP treatment. AFP did not compete with agonists for the estrogen receptor. These laboratory results are consistent with the findings of a literature search, which consistently showed an association between elevated pregnancy levels of AFP and subsequent reduced risk for breast cancer later in life. We conclude that AFP can inhibit growth of estrogen-dependent breast cancer and warrants further development as an agent for the treatment and perhaps even the prevention of human breast cancer.

Animals↗
PubMed1997

Similarity between natural and recombinant human alpha-fetoprotein as inhibitors of estrogen-dependent breast cancer growth.

Alpha-fetoprotein (AFP) isolated from rodent amniotic fluid or human cord sera, upon incubation with a molar excess of estradiol, is converted to a form which inhibits estrogen-stimulated tissue growth. The purpose of this study was to determine whether recombinant human AFP produced in an E. coli expression system retained this function. The recombinant protein was similar to the natural protein isolated from pooled human cord sera in all functional aspects evaluated. It was detected by monoclonal and polyclonal antibodies to the natural protein. Following exposure to estradiol, it was converted to an inhibitor of estrogen-stimulated growth of immature mouse uterus yielding a dose/response curve similar to that of the natural protein. It inhibited the growth of estrogen-dependent (MCF-7) but not estrogen-independent (MDA-MB-231) breast cancer xenografts with the same schedule dependency and resultant histological changes as the natural protein. Availability of large quantities of homogeneous, biologically active recombinant human AFP will facilitate further studies of structure/function, mechanism, and therapeutic potential of this agent as a regular of breast cancer growth.

Animals↗
PubMed1997

Difficult or impossible ventilation after sufentanil-induced anesthesia is caused primarily by vocal cord closure.

INTRODUCTION: Opioid-induced rigidity often makes bag-mask ventilation difficult or impossible during induction of anesthesia. Difficult ventilation may result from chest wall rigidity, upper airway closure, or both. This study further defines the contribution of vocal cord closure to this phenomenon. METHODS: With institutional review board approval, 30 patients undergoing elective cardiac surgery participated in the study. Morphine (0.1 mg/kg) and scopolamine (6 microg/kg) given intramuscularly provided sedation along with intravenous midazolam as needed. Lidocaine 10% spray provided topical anesthesia of the oropharynx. A fiberoptic bronchoscope positioned in the airway photographed the glottis before induction of anesthesia A second photograph was obtained after induction with 3 microg/kg sufentanil administered during a period of 2 min. A mechanical ventilator provided 10 ml/kg breaths at 10/min via mask and oral airway with jaw thrust. A side-stream spirometer captured objective pulmonary compliance data. Subjective airway compliance was scored. Pancuronium (0.1 mg/kg) provided muscle relaxation. One minute after the muscle relaxant was given, a third photograph was taken and compliance measurements and scores were repeated. Photographs were scored in a random, blinded manner by one investigator. Wilcoxon signed rank tests compared groups, with Bonferroni correction. Differences were considered significant at P < 0.05. RESULTS: Twenty-eight of 30 patients exhibited decreased pulmonary compliance and closed vocal cords after opioid induction. Two patients with neither objective nor subjective changes in pulmonary compliance had open vocal cords after opioid administration. Both subjective and objective compliances increased from severely compromised values after narcotic-induced anesthesia to normal values (P = 0.000002) after patients received a relaxant. Photo scores document open cords before induction, progressing to closed cords after the opioid (P = 0.00002), and opening again after a relaxant was administered (P = 0.00005). CONCLUSION: Closure of vocal cords is the major cause of difficult ventilation after opioid-induced anesthesia.

Humans↗
PubMed1997

Time course and relative dose potency of systemic effects from salmeterol and salbutamol in healthy subjects.

BACKGROUND: The main adverse effects of beta 1 agonists relate to their systemic activity. The time course and dose response relations of the systemic effects of salmeterol compared with salbutamol were investigated. METHODS: A double blind, randomised, crossover study was carried out in 14 healthy subjects who attended on seven days. Heart rate, QTc interval, blood pressure, plasma potassium and glucose concentrations were measured for four hours following inhaled placebo, salmeterol 100, 200 and 400 micrograms and salbutamol 600, 1200 and 2400 micrograms given by metered dose inhaler. Maximum changes from baseline and maximum absolute values following each dose of treatment were used to construct log dose response curves and calculate relative dose potency. RESULTS: Both salmeterol and salbutamol caused dose dependent changes in heart rate, QTc interval, and plasma potassium and glucose concentrations. The onset of cardiac effects was rapid following both drugs, whereas changes in glucose and potassium concentrations occurred more gradually with salmeterol. The increase in heart rate and fall in potassium level were sustained over the four hours whereas glucose levels gradually returned towards baseline. The relative dose potency of salmeterol compared with salbutamol for changes from baseline was 7.1 (95% CI 3.9 to 14.4) for the QTc interval and 8.2 (95% CI 5.7 to 12.6) for plasma potassium concentration. Salmeterol caused steeper dose response curves for heart rate and plasma glucose concentration than salbutamol so relative dose potency values could not be calculated. CONCLUSIONS: These findings support previous data that salmeterol 100 micrograms is broadly equivalent to salbutamol 800 micrograms for systemic effects. The greater systemic effects of salmeterol are most likely to be due to greater potency relative to dose, although it may also have greater systemic bioavailability. The steeper dose response curve for heart rate with salmeterol indicates that it has a narrower therapeutic window than salbutamol and thus should be prescribed at the lowest effective dose.

Adrenergic beta-Agonists↗
PubMed1997

A case for theory triangulation.

Although theory triangulation has not received much attention in the nursing literature, its deliberate, strategic use can be an invaluable guide to reviewing literature and designing research. It can enlarge the framing of questions for orderly data collection and analysis, and can lay out a route for rational, coherent study-clustering. An example is presented that triangulates two nursing theories to address a frequently studied problem--nurses' attitudes about AIDS care. The absence of firm theoretical footing in exploring this problem has limited the application of a large, continuously growing body of empirical data. Triangulation is suggested to organize these data, to clarify apparently inconsistent findings, and to guide research. The example demonstrates how the exploration of related questions not addressed by a single theory may be aided by searching for linkages among mid-range theories, including theories from other disciplines.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Expression of human lecithin:cholesterol acyltransferase in transgenic mice: effects on cholesterol efflux, esterification, and transport.

Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the plasma metabolism of cholesterol and is postulated to participate in a physiologic process called reverse cholesterol transport. We have used transgenic mice expressing the human LCAT transgene to study the effect of increased plasma levels of LCAT in each of the proposed steps involved in the reverse cholesterol transport pathway. High density lipoprotein (HDL) from LCAT transgenic mice was 44% more efficient than control mouse HDL in the efflux of cholesterol from human skin fibroblasts. Esterification of cell-derived cholesterol was also markedly increased in mice expressing the human LCAT transgene. The rate of plasma clearance of HDL cholesteryl ester was virtually the same in both types of animals whereas the HDL cholesteryl ester transport rate was significantly increased in mice expressing the human LCAT transgene (152.3 +/- 16.9 micrograms/h vs. 203.1 +/- 30.9 micrograms/h in control and transgenic mice, respectively). Liver cholesteryl ester uptake was significantly increased in mice expressing human LCAT (58.0 +/- 1.4 micrograms/h/g liver vs. 77.9 +/- 1.7 micrograms/h/g liver in control and transgenic mice, respectively). These studies indicate that LCAT modulates the rate by which cholesterol is effluxed from cell membranes onto HDL, esterified, and transported to the liver.

Animals↗