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Biomedical subjects

E M Taylor

Publications and source records attributed to E M Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1991

Amiloride sensitivity of chorda tympani response to NaCl in Fischer 344 and Wistar rats.

Fischer 344 (F-344) rats fail to prefer NaCl solutions to water at any concentration and avoid NaCl solutions preferred by other strains, including Wistar rats. Behavioral and electrophysiological responses of the mammalian gustatory system to NaCl have been shown to depend on a sodium transport system that is specifically blocked by lingual application of the sodium-transport blocker amiloride. The present study examined whether strain differences exist between F-344 and Wistar rats in the amiloride sensitivity of the chorda tympani (CT) electrophysiological response to NaCl. Whole nerve CT recordings were obtained from adult F-344 and Wistar rats during chemical stimulation of the anterior tongue. Responses to NaCl solutions ranging from 0.01 to 1.0 M were examined both before and after pretreatment with amiloride hydrochloride. Integrated whole nerve responses to NaCl solutions were expressed relative to the response to 0.5 M NH4Cl. Strain differences in the response to NaCl solutions emerged, with F-344 animals showing a significantly larger amplitude of the tonic response to NaCl, relative to NH4Cl, than Wistars. F-344 rats were also more sensitive to the sodium-channel blocker amiloride. These results suggest that strain differences in amiloride sensitive signals mediated by the CT nerve may contribute to the NaCl aversion displayed by F-344 rats.

Amiloride↗
PubMed1990

Developmental changes in transferrin and iron uptake by the brain in the rat.

The uptake of transferrin and iron by the brain, liver and femurs was investigated in rats using 125I-59Fe-transferrin (Tf), and 131I-albumin in order to measure the plasma content of the organs. Measurements in rats ranging in age from birth to 70 days revealed that the rate of iron uptake by the brain increased rapidly over the first 15 days of life, peaking at 15 days and thereafter declining. A similar pattern occurred in the uptake of 125I-Tf. These changes were accompanied by rapid growth of the brain up to 15 days and a decrease in the concentration of non-haem iron. The turnover of 59Fe and 125I-Tf in the brain was also determined by measuring radioactivity in the brain of 15-day rats at various times after injection from 15 min to 13 days. The amount of 59Fe in the brain increased over the first 4 h and thereafter remained constant. By contrast, the 125I-Tf values increased rapidly during the first 15 min to reach a relatively constant level which was maintained for at least 6 h after which it declined. The patterns of uptake by the brain were different from those found in the liver and femurs, indicating that the changes in the brain were specific for that organ.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Decline in breast feeding.

Information on whether mothers intended to breast feed and whether they actually did so one month after delivery has been recorded for all mothers in Sheffield during the last 15 years, and changes in the last 10 years have been reported. There was a steady increase in the percentage of mothers intending to breast feed and in those who did so in the 1970s. From 1984-8, however, there has been a rapid and progressive decline, despite an increase in mean maternal age and a reduction in the number of non-white births. The decline in the percentage of mothers who intend to breast feed has been greatest among those whose education did not extend beyond the age of 18, and among Asian mothers.

Adult↗
PubMed1990

Categories of preventable unexpected infant deaths.

The conclusions of confidential inquiries into 115 registered unexpected infant deaths over a period of nine years were reviewed. Deaths were classified based on the total information available into group A: poor prognosis (n = 7), group B: treatable disease (n = 45), group C: minor disease (n = 32), group D: no disease (n = 19), group E: probably accidental (n = 4), and group F: probably filicide (n = 8). Less than 20% of deaths corresponded to the classic definition of sudden infant death syndrome (SIDS). Babies who died during the course of potentially treatable disease had more adverse family and social factors: the parents were less likely to be owner occupiers, or own a car or telephone, their mothers were more likely to be young, to smoke, and to present late in pregnancy. Babies who died of minor disease tended to come from similar backgrounds, their families had greater levels of stress and the deaths appeared to be due to more than one factor. Babies who died with no terminal disease were younger, and more likely to be boys. Their families appeared to be demographically similar to those of a control group and to the general population.

England↗
PubMed1989

Adrenergic and purinergic neurotransmission in arterial resistance vessels of the cat intestinal circulation.

The contribution of adrenoceptors and purine receptors in mediating neurogenic vasoconstriction was investigated in the autoperfused intestinal circulation of anaesthetised cats treated with atropine and propranolol. Prazosin (0.5 mg/kg) and yohimbine (1.5 mg/kg) reduced but did not abolish the vasoconstrictor responses to stimulation of the efferent sympathetic nerves. The inhibitory actions of the two antagonists were additive but even after alpha 1- and alpha 2-adrenoceptor blockade nerve stimulation still elicited a residual, frequency-related vasoconstriction. The initial, rapid, phase of this response was completely abolished after desensitisation of P2x-purinoceptors with a high dose (1.5 mg i.a.) of alpha,beta-methylene ATP. In the absence of alpha-adrenoceptor antagonists, alpha,beta-methylene ATP reduced neurogenic vasoconstriction particularly at low frequency (1 Hz) nerve stimulation, but also caused a short-lasting decrease in noradrenaline and methoxamine responses which indicates that the drug may have some non-specific effects on arterial smooth muscle. The results suggest that neurotransmission in arterial resistance vessels of the cat intestinal circulation is predominantly under adrenergic control mediated by postsynaptic alpha 1- and alpha 2-adrenoceptors, with a possible purine involvement in the initial rapid response of the blood vessels, particularly to low frequency nerve stimulation.

Adenosine Triphosphate↗
PubMed1989

The effects of adenosine triphosphate and related purines on arterial resistance vessels in vitro and in vivo.

The distribution of P2-purinoceptors in pre-capillary resistance vessels was studied in vitro, using Krebs perfused rabbit ears and in vivo, in autoperfused hindquarters, intestinal and renal vasculatures of pentobarbitone anaesthetised cats. ATP (10(-10)-10(-6) mol i.a.) caused dose-dependent vasodilatation which, in the rabbit ear, was antagonised by reactive blue 2 (10(-5)-10(-4) M). At the highest concentration of reactive blue 2, ATP responses were reversed and a dose-dependent vasoconstriction was seen. Reactive blue 2, also reduced the vasodilator responses to carbachol and to a lesser extent papaverine which suggests that the antagonist has limited selectivity. The rank order of potency of ATP analogues as vasodilators, 2-methylthio ATP greater than ADP greater than ATP greater than alpha,beta-methylene and beta,gamma-methylene ATP, suggests P2y purinoceptors are involved. The selective P2x-purinoceptor agonist, alpha,beta-methylene ATP, caused pronounced vasoconstriction in the rabbit ear and cat intestinal vasculature which was not antagonised by phenoxybenzamine. In contrast, alpha,beta-methylene ATP had little effect in the autoperfused hindquarters and renal vasculatures suggesting a very heterogeneous distribution of P2x-purinoceptors in the cat. The results are consistent with the proposal that two distinct types of P2-purinoceptors are present on blood vessels.

Adenosine Triphosphate↗
PubMed1988

Trends in unexpected infant deaths in Sheffield.

A study of 250 post-perinatal deaths in Sheffield during the past 8 years has shown an increased rate of unexpected infant death. This increase appears to be mainly caused by deaths in children with minor disease in families where the father is either absent or unemployed. The number of children who die during the course of more serious disease continues to fall. The number of infant deaths from other causes is unchanged.

Cause of Death↗
PubMed1988

Radiation, methotrexate, and white matter necrosis: laboratory evidence for neural radioprotection with preirradiation methotrexate.

To investigate the interactions between methotrexate (MTX) and irradiation of the central nervous system, adult rats were infused with MTX via the lateral cerebral ventricle either before, during, or following single fraction irradiation to the cervical spine. Single doses ranging from 1600 cGy to 3200 cGy were administered and the dose-response curve for forelimb paralysis was compared with that seen in irradiated animals which did not receive MTX. There was no effect on the dose-response curve when MTX was administered simultaneously with or following irradiation compared to radiation alone. When MTX was given prior to irradiation, however, the entire dose-response curve shifted in the direction of radioprotection by approximately 225 cGy. Histopathologic examinations were consistent with this observation, with animals pretreated with methotrexate demonstrating significantly less white matter necrosis than observed in untreated controls. Protection of normal CNS tissue from radionecrosis, and from the associated paralysis, may be achieved with preradiation methotrexate.

Animals↗
PubMed1988

Design and synthesis of a series of combined vasodilator/beta-adrenoceptor antagonists based on 6-arylpyridazinones.

A series of new 6-[4-[[(aryloxy)acyl]amino]phenyl]-4,5-dihydropyridazinones have been synthesized and evaluated as combined vasodilator/beta-adrenoceptor antagonists and potential antihypertensive agents. Many of the early compounds displayed an unacceptably high level of intrinsic sympathomimetic activity (ISA) and a relatively short duration of action. Disubstitution in the 2,3-positions or in the 4-position of the aryloxy ring gave compounds with low ISA levels and, in some instances, improved duration of action. All of the compounds were vasodilators, but the 5-methylpyridazinone derivatives showed consistently greater antihypertensive activity than their 5-H lower homologues. Further detailed pharmacological investigations led to the selection of 6-[4-[3-[[2-hydroxy-3-[4-[2- (cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]propionamido] phenyl]- 5-methyl-4,5-dihydro-3(2H)-pyridazinone (4t) (SK&F 95018) as a development candidate.

Adrenergic beta-Antagonists↗
PubMed1988

In vivo pharmacological studies with SK&F 94836, a potent inotrope/vasodilator with a sustained duration of action.

1. SK&F 94836 (racemate) was studied in vivo for its cardiovascular properties in cats and dogs. 2. In anaesthetized cats and dogs SK&F 94836 administered intravenously caused increases in left ventricular contractility and decreases in peripheral vascular resistance at similar doses, thus demonstrating the compound to be a mixed acting positive inotropic/vasodilator agent. 3. In conscious instrumented dogs SK&F 94836 was active via the oral as well as intravenous route. 4. The inodilator activity of SK&F 94836 in conscious and anaesthetized animals occurred in association with minimal changes in either blood pressure or heart rate. 5. Detailed studies carried out on anaesthetized cats indicated that SK&F 94836 caused a balanced dilatation of both resistance and capacitance blood vessels. 6. Haemodynamic studies in anaesthetized cats indicated that as a consequence of the inotropic/vasodilator actions, SK&F 94836 caused significant increases in cardiac output and stroke volume. 7. Detailed studies in anaesthetized dogs indicated that significant inodilator activity occurred in the absence of an increase in myocardial oxygen consumption. 8. The duration of action of SK&F 94836 was sustained following both i.v. and oral administration. 9. We conclude that SK&F 94836, as an orally active inotropic/vasodilator agent with a sustained duration in vivo, has potential utility in the treatment of congestive heart failure.

Anesthesia↗
PubMed1988

Prevention of unexpected infant death. A review of risk-related intervention in six centers.

Over seventy percent of unexpected infant deaths are registered as SIDS. Over 85,000 infants have been screened at birth and one month of age for risk of unexpected death using the Sheffield Score system. Scores range from below 400 to over 800 points. Infants with scores over 800 are at more than 16 times greater risk than infants with scores below 400. Family doctors and health visitors were alerted to high-risk infants, who were examined at home and weighed naked at home five times in the first six months. Mortality in the high-risk group was reduced by more than 50% (p less than 0.02 in one area and p less than 0.05 in another). It is concluded that with few extra resources unexpected infant mortality can be reduced by 25% by this approach.

Child Health Services↗
PubMed1988

Rodent model of chemoradiotherapy-induced white matter necrosis.

This report describes a laboratory model that permits study of the radiochemotherapy interactions in the CNS. Rats are stereotaxically implanted with a cerebroventricular cannula attached to an osmotic minipump, which slowly infuses a chemotherapeutic agent into CSF for up to 14 days. The cervical cord is irradiated, and forelimb paralysis develops 4-6 months later at an effective dose for paresis in 50% of the animals; the doses with radiotherapy alone are 2,125 cGy for a single fraction and 2,950 cGy for split fractions. Investigations with the model indicate that mature CNS tissue is not sensitized to either single-fraction or split-dose irradiation with either simultaneous or post-radiation exposure to high concentrations of methotrexate.

Animals↗
PubMed1987

SK & F 95018, a vasodilator/beta-adrenoceptor antagonist.

The pharmacological properties of a novel vasodilator/beta-adrenoceptor antagonist, SK & F 95018 6-[4-[3-(3-[4-(2-Cyclopropylmethoxyethyl)phenoxy]-2- hydroxypropylamino)propionamido]phenyl]-4,5-dihydro-5-met hylpyridazin- 3(2H)-one methanesulphonate] are described. SK & F 95018 lowered blood pressure and increased hindquarters blood flow in anaesthetised rats over the same dose range 1-5 mumol kg-1. Over a similar dose range SK & F 95018 inhibited isoprenaline-induced tachycardia in ganglion-blocked, anaesthetized cats. SK & F 95018 had minimal effect on bronchial beta 2-adrenoceptors, while simultaneously antagonizing cardiac beta 1-adrenoceptors in anaesthetized guinea-pigs. SK & F 95018 was demonstrated to be a potent antihypertensive agent in conscious spontaneously hypertensive rats over the dose range of 1.6-13 mumol kg-1 i.v. and 13-103 mumol kg-1 p.o. A marked and persistent hypotension was observed in conscious cats at a dose of 7.5 mumol kg-1 i.v. and 19 mumol kg-1 p.o., without reflex tachycardia. In anaesthetized cats, the hypotensive response to the compound was found to be via a reduction in total peripheral resistance with a maintained cardiac output. Vasodilatation and beta-adrenoceptor antagonism have been demonstrated in the same molecule (SK & F 95018) in a combination which would be suitable for effective treatment of hypertension.

Adrenergic beta-Antagonists↗
PubMed1986

Microwave sterilization of hydrophilic contact lenses.

We used standard 2,450-MHz microwave irradiation to achieve sterilization of hydrophilic contact lenses contaminated with a variety of bacterial, fungal, and viral corneal pathogens. A three-dimensional rotisserie was used to overcome the problem of "cold spots" within the microwave oven. The contact lenses became dehydrated in approximately two minutes. Rehydration with normal saline restored their shape and appearance. The time necessary to prohibit all growth of the bacterial and fungal organisms studied ranged from 45 seconds to eight minutes. All viral contaminants were completely inactivated after four minutes of microwave exposure. Refractive properties were unaffected after 101 exposures to microwaves for ten minutes. Slit-lamp examination and scanning electron microscopy disclosed minute particles on the surface of these contact lenses but no damage to the lens matrix from irradiation.

Bacteria↗
PubMed1986

Pharmacological studies with SK&F 94120, a novel positive inotropic agent with vasodilator activity.

The pharmacological properties of SK&F 94120 on the cardiovascular system have been studied in laboratory animal species. The compound was shown to have positive inotropic activity on hearts from guinea-pig, cat, dog and marmoset in-vitro and in cat and dog in-vivo. These responses in-vivo occurred in association with minimal changes in heart rate. Positive inotropic activity was not caused by SK&F 94120 in rat or hamster hearts in-vitro, thereby indicating a species dependence in myocardial response. SK&F 94120 was shown to have vasodilator activity in cats in-vivo. Detailed studies carried out on anaesthetized cats indicated that the compound caused a balanced dilatation of both resistance and capacitance blood vessels. Haemodynamic studies in anaesthetized cats indicated that, as a consequence of the positive inotropic and vasodilator actions, SK&F 94120 causes significant increases in cardiac output and stroke volume. Studies in conscious dogs showed the compound to be active as a positive inotrope after oral administration. The above properties suggest that this compound possesses useful haemodynamic properties for the treatment of congestive heart failure.

Animals↗