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Biomedical subjects

E M Taylor

Publications and source records attributed to E M Taylor.

At least 19 recordsLinked to original sources

Height velocity screening: the real world.

To assess the value of the Middlesex-Height Velocity Screening Chart (based on the 50th velocity percentile +/- 1 SD) as a means of screening for abnormal growth in children, the heights of children at seven infant schools were measured on two separate occasions at least 12 months apart. A total of 229 children of mid-age (age of the child between the two measurements) ranging from 4.5 to 6.8 years were measured. Height velocity standard deviation score was calculated for each child by comparison with current Tanner-Whitehouse standards. The subjects were children who had a height recorded during the school entrant medical at least 12 months before the date of the second height measurement. The height velocity standard deviation score calculated for each child was related to the limits set by the Middlesex Screening Chart, and these criteria were used to determine whether or not the child had a 'normal' growth rate. It has been recommended that those falling outside these limits are referred for further assessment. It was found that 95 (41 percent) children fell outside the 'normal' range on the Middlesex chart (66 growing faster and 29 slower), which, if the guidelines were used uncritically, would result in the possible referral of 2500 5-6-year-olds in Sheffield alone. Taking into consideration the additional problems inherent in making two accurate height measurements from which a height velocity could be calculated, and the high number of referrals that would be generated as demonstrated by this study, height velocity screening for growth disorders using current methods is not feasible.

Anthropometry

Potentiation of responses to sympathetic nerve stimulation and vasoconstrictor agents by SK&F 103829 in the feline mesenteric circulation.

1. The amplification of vasoconstrictor effects of several agonists and sympathetic nerve stimulation, caused by 5-HT2 receptor activation, was studied in the autoperfused mesenteric circulation of anaesthetized cats. To produce long lasting and selective 5-HT2 receptor stimulation we used SK&F 103829 (2,3,4,5 tetrahydro-8[methyl-sulphonyl]-1H3-benzazepin-7-ol methensulphonate). We assessed that SK&F 103829 was a strong contractile partial agonist in isolated preparations of rat tail artery and calf pulmonary artery. 2. The intrinsic activity of SK&F 103829 with respect to 5-hydroxytryptamine (5-HT) was 0.8 in rat tail artery and 0.6 in calf pulmonary artery. SK&F 103829-induced contractile responses were surmountably antagonized by ketanserin with a potency expected from its affinity for 5-HT2 receptors. SK&F 103829 surmountably antagonized the effects of 5-HT in rat tail artery with a pKp of 5.8. 3. Concentrations of SK&F 103829 causing greater than threshold constrictions enhanced vasoconstrictor responses of sympathetic nerve stimulation, noradrenaline, angiotensin II, methoxamine and alpha, beta-methylene ATP in the mesenteric arterial bed. Increases in mesenteric arterial pressure by noradrenaline, observed in the presence of prazosin, were also potentiated by SK&F 103829. 4. Ketanserin prevented both the constrictor effect of SK&F 103829 and the SK&F 103829-evoked potentiation of the responses to noradrenaline and angiotensin II in the mesenteric arterial bed. Ketanserin, however, failed to abolish (once established) the SK&F 103829-evoked potentiation of the constrictor effects caused by both noradrenaline and angiotensin II. 5. Short lasting constrictor effects of 5-HT were reversed to dilator effects by SK&F 103829 in both the mesenteric arterial and venous bed, thereby revealing the existence of vasodilator 5-HT receptors.6. The main finding is consistent with a sensitization of the mesenteric arterial bed to vasoconstrictor responses mediated through alpha 1- and alpha2-adrenoceptors, angiotensin II receptors and purinoceptors by SK&F 103829-evoked activation of 5-HT2 receptors. This property, together with the direct constrictor effect of the mesenteric arterial bed suggest that SK&F 103829 can reduce portal venous flow thereby being a useful therapeutic principle for the treatment of portal hypertension.

Animals

Area postrema mediation of physiological and behavioral effects of lithium chloride in the rat.

The area postrema (AP), a chemoreceptor trigger zone for nausea and vomiting, has been implicated in taste aversion conditioning with LiCl. In addition to taste aversion acquisition, the present studies indicate that a number of other responses to LiCl administration are eliminated by lesions of the AP. These include a behavioral response, 'lying-on-belly' as well as two physiological responses, delayed stomach emptying and hypothermia. These findings suggest that the area postrema is critically involved in the detection of LiCl and in a wide range of responses to this toxin. They also provide strong evidence that the failure to acquire conditioned taste aversions to LiCl-paired flavors after AP lesions can be attributed to the absence of a significant 'illness' response in lesioned animals.

Animals

Amiloride sensitivity of the chorda tympani response to sodium chloride in sodium-depleted Wistar rats.

Peripheral gustatory mechanisms that may contribute to the expression of sodium (Na) appetite have been a focus of interest for many years. Because amiloride-sensitive Na transport is involved in the generation of neural signals in response to NaCl stimulation, the present study assessed whether changes in amiloride sensitivity of the neural response to NaCl accompany the induction of a Na appetite in the rat. Na deprivation was achieved by acute depletion with the diuretic furosemide. The magnitude of the whole-nerve chorda tympani response to 0.5 M NaCl was reduced in Na-depleted, compared with Na-replete, rats, which provides qualified support for previous reports that the induction of a Na appetite is associated with reduced neural responses to NaCl. However, changes in sensitivity to the specific Na channel blocker amiloride hydrochloride as a result of Na depletion were not evident. These findings suggest that the behavioral and neural changes that occur after Na depletion are not based on changes in amiloride sensitivity in the taste bud.

Amiloride

Effects of alpha,beta-methylene ATP on resistance and capacitance blood vessels of the cat intestinal circulation; a comparison with other vasoconstrictor agents and sympathetic nerve stimulation.

The autoperfused intestinal circulation of pentobarbitone anaesthetized cats was used to study the effects of alpha,beta-methylene ATP (1-100 micrograms i.a.) on pre-capillary resistance vessels and post-capillary capacitance (venous) blood vessels in comparison with other vasoconstrictor agents (also given i.a.) and the effects of sympathetic nerve stimulation (0.25-16 Hz). All cats were treated with atropine and propranolol. alpha,beta-Methylene ATP, noradrenaline and sympathetic nerve stimulation all caused dose- or frequency-dependent constriction of both resistance and capacitance vessels. alpha,beta-Methylene ATP was particularly active on capacitance vessels causing a greater constriction than either noradrenaline or sympathetic nerve stimulation. In comparison, angiotensin II and vasopressin caused a selective constriction of resistance vessels and prostaglandin F2 alpha a selective constriction of capacitance vessels. The results demonstrate that functional P2x purinoceptors are present on both arterial and venous blood vessels of the cat intestinal circulation.

Adenosine Triphosphate

The effect of age on the latency of radiation myelopathy.

The latent period to forelimb paresis following photon irradiation of the cervical spinal cord was evaluated in Sprague-Dawley rats ranging in age from 9 days to adulthood. The radiation was administered dorsally in single fractions, and in 15-day-old animals, to different lengths of the rostral cord and in doses ranging from 16 to 38 Gy. The duration of the latent period was found to be directly proportional to the age of the animal at the time of irradiation, and independent of radiation dose or the volume of the cervical cord which was irradiated. In the majority of paretic animals, the irradiated segment of the spinal cord demonstrated white matter necrosis. The results indicate that in the developing rat, the manifestations of radiation myelopathy are delayed by an interval determined in part by the age of the animal at the time of irradiation.

Age Factors

Role of transferrin in iron uptake by the brain: a comparative study.

The role of specific transferrin (Tf) and Tf receptor interaction on brain capillary endothelial cells in iron transport from the plasma to the brain was investigated by using Tf from several species of animals labeled with 59Fe and 125I, and 15-day and adult rats. The rate of iron transfer was much greater in the 15-day rats. It was greatest with Tf from the mammals, rat, rabbit and human, but much lower with chicken ovotransferrin and quokka (a marsupial), toad, lizard, crocodile, and fish Tf. The uptake of Tf by the brain showed a similar pattern, except for a very high uptake of ovotransferrin (ovoTf). Iron uptake by the femurs (a source of bone marrow) was also high with Tf from the mammalian species and low with the other types of Tf, but showed little change with aging of the animals. It is concluded that iron transport into the brain is dependent on the function of Tf receptors, probably on capillary endothelial cells, and that these receptors show the same type of species specificity as the receptors on immature erythroid cells. Also, the decrease in iron uptake by the brain as rats age from 15 days to adulthood is specific for the brain and is not a general effect of the aging process.

Alligators and Crocodiles

Transferrin and iron uptake by the brain: effects of altered iron status.

Transferrin (Tf) and iron uptake by the brain were measured in rats using 59Fe-125I-Tf and 131I-albumin (to correct for the plasma content of 59Fe and 125I-Tf in the organs). The rats were aged from 15 to 63 days and were fed (a) a low-iron diet (iron-deficient) or, as control, the same diet supplemented with iron, or (b) a chow diet with added carbonyl iron (iron overload), the chow diet alone acting as its control. Iron deficiency was associated with a significant decrease and iron overload with a significant increase in brain nonheme iron concentration relative to the controls. In each dietary treatment group, the uptake of Tf and iron by the brain decreased as the rats aged from 15 to 63 days. Both Tf and iron uptake were significantly greater in the iron-deficient rats than in their controls and lower in the iron-loaded rats than in the corresponding controls. Overall, iron deficiency produced about a doubling and iron overload a halving of the uptake values compared with the controls. In contrast to that in the brain, iron uptake by the femurs did not decrease with age and there was relatively little difference between the different dietary groups. 125I-Tf uptake by the brains of the iron-deficient rats increased very rapidly after injection of the labelled proteins, within 15 min reaching a plateau level which was maintained for at least 6 h. The uptake of 59Fe, however, increased rapidly for 1 h and then more slowly, and in terms of percentage of injected dose reached much higher values than did 125I-Tf uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

TNF-induced anorexia and learned food aversions are attenuated by area postrema lesions.

Tumor necrosis factor (TNF) or cachectin has been proposed as an important mediator of cancer anorexia and cachexia. The present studies examined the extent to which TNF administration generates symptoms similar to those produced by tumor growth. Like the growth of certain tumors, TNF administration was found to be associated with the development of strong aversions to a novel diet. Area postrema lesions were found to significantly attenuate the effects of TNF on intake of a novel diet, a finding previously reported for tumor anorexia. In addition, the anorexic effects of TNF differed considerably as a function of the novelty of the diet. When the available diet was novel, effects of TNF in lowering food intake were substantial, whereas more modest effects were seen when the diet was familiar. These findings provide evidence for parallels between TNF- and tumor-induced anorexias. Nonetheless, these studies also confirm previous observations of the rapid development of tolerance to the anorexic effects of TNF, a finding that is not consistent with a role for TNF as a critical mediator of tumor anorexia.

Animals

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

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

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

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

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

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

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