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Biomedical subjects

J Atkinson

Publications and source records attributed to J Atkinson.

At least 91 records · Page 5Linked to original sources
PubMed1986

Oxitropium bromide. Dose-response and time-response study of a new anticholinergic bronchodilator drug.

The efficacy and side effects of oxitropium bromide, a new anticholinergic bronchodilator drug, were tested in a double-blind placebo-control study. Twenty-four men, aged 58 to 72 years, with chronic partially reversible obstruction of the airways were used as subjects. Three doses of oxitropium were tested (100 micrograms, 200 micrograms, and 300 micrograms) to determine the optimum dose by metered-dose inhaler. A comparison was also made between oxitropium, fenoterol (400 micrograms), and a combination of oxitropium (200 micrograms) and fenoterol (400 micrograms). Fenoterol produced a greater degree of maximal bronchodilatation than each of the three doses of oxitropium, and its effect was more rapid in onset (30 vs 120 minutes to peak effect); however, the duration of action of oxitropium was greater than that of fenoterol (ie, the forced expiratory volume in one second [FEV1] remained within 5 percent of peak FEV1 for three hours, compared to one hour). Oxitropium in the 100 micrograms dose was inferior to 200 micrograms and 300 micrograms in subjective efficacy scores, peak percent change in FEV1, forced vital capacity, (FVC), mean forced expiratory flow over the middle half of the FVC, and duration of action; there was no difference between 200 micrograms and 300 micrograms. The oxitropium-fenoterol combination had a rapid onset of action, and a greater peak effect was achieved than for oxitropium alone. The main unwanted effect was a mildly unpleasant taste. Anticholinergic effects were not seen in this group of elderly men. Oxitropium bromide therefore is an effective bronchodilator with slow onset but prolonged activity and few side effects when used in patients with moderately severe obstruction of the airways. An appropriate dose appears to be 200 micrograms. Addition of oxitropium to fenoterol appears to offer even greater efficacy.

Aged↗
PubMed1986

[Reduced sensitivity to noradrenaline and electric stimulation of the caudal artery of the aged rat].

UNLABELLED: Whilst arterial noradrenaline (NOR) content decreases with age (Waterson, et al. 1974; Neubauer and Christensen, 1978; Embree, et al., 1981), changes in vasoconstriction induced by NOR are equivocal (Tuttle, 1966; Cohen and Berkowitz, 1976; Scott and Reid, 1982; Duckles, et al., 1985). We have investigated changes in responsiveness to NOR in the NOR-rich rat tail artery. Two cm segments of the proximal tail artery from male Ivanos rats of 6/7, 16/17 or 30/31 months were perfused/superfused with Krebs bicarbonate (4 ml/min). Changes in perfusion pressure (mmHg) were determined after (1) electrical stimulation (1 to 30 Hz, 0.3 msec, 15 sec at supramaximal voltage, ES) followed by (2) perfusion with exogenous NOR (1 nM to 10 microM for 2 min at each concentration). Responses to ES were abolished by pretreatment with reserpine (2.5 mg/kg, i.p. at - 18 h) or perfusion with phentolamine (4 microM). They were produced therefore, by liberation of endogenous NOR. Arterial NOR content was determined by HPLC-EC following perchloric acid digestion (0.1 N). RESULTS: (Table: see text). Asterisks refer to t-test with 6/7 months age group (p less than 0.05, p less than 0.01 and p less than 0.001]. There were no differences in basal perfusion pressure before stimulation or in plateaux responses to maximal concentrations of NOR. In conclusion our results show a decrease in arterial NOR and in sensitivity to both endogenous and exogenous NOR with age.

Aging↗
PubMed1985

Attenuation of the baroreceptor reflex by general anesthetic agents in the normotensive rat.

We have investigated the effects of urethane, a urethane + allobarbital mixture, alpha-chloralose and sodium pentobarbital on baroreceptor reflex function in the normotensive rat. Results were compared to those obtained in the conscious rat. Baroreceptor reflex function was evaluated from the fall in heart rate which accompanied the rise in diastolic arterial pressure following intravenous administration of phenylephrine. All four anesthetic agents attenuated reflex function as shown by a decrease in the bradycardiac response. There was a four to five-fold attenuation with urethane and urethane + allobarbital and a two- to three-fold attenuation with alpha-chloralose and sodium pentobarbital.

Anesthetics↗
PubMed1985

The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: evidence for spare myocardial beta receptors.

We have compared and contrasted the actions of (-)isoproterenol and (+/-) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5'-(beta, gamma imino) triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC15) were 2.0 X 10(-7) M and 5.5 X 10(-8) M for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]p EC30 values were 2.0 X 10(-7) and 3.5 X 10(-8) M for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5 X 10(-7) M and 1.7 X 10(-8) M for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1985

Involvement of the renin-angiotensin system in the dipsogenic effect of morphine.

This paper examined whether drinking elicited by morphine is dependent upon an intact renin-angiotensin system. Bilateral nephrectomy, carried out one day prior to administration of morphine, completely abolished morphine-induced water intake, pointing to involvement of the kidneys in the dipsogenic effect of morphine. Plasma and renal renin depletion were induced by the clipping of one renal artery followed, one month later, by removal of the clipped kidney. In such renin-depleted rats with subnormal plasma renin levels, morphine and isoprenaline-induced water intakes were linearly related to pre-injection basal plasma renin level. Such a relationship was not found in rats with normal renin levels. These results pointed to the existence of a permissive interaction between morphine and the renin-angiotensin system. Captopril, an inhibitor of the angiotensin converting enzyme, increased morphine-induced water intake. We interpreted this drinking response as being the sum of morphine-induced drinking (following a permissive interaction between morphine and circulating angiotensin I or renin) and captopril-induced drinking (following a captopril-induced increase in circulating renin and angiotensin I levels). The competitive antagonist of angiotensin II, saralasin, had no effect on morphine-induced drinking. This result pointed once again to a permissive interaction between morphine and circulating angiotensin I or renin.

Animals↗
PubMed1984

Changes in central monoaminergic function during chronic treatment with clonidine in the spontaneously hypertensive rat.

Clonidine was administered intravenously via osmotic minipumps at doses of 0.1 and 0.5 mg X kg-1 X 24 h-1. Both doses lowered blood pressure to the same degree by the third day of treatment. Only the higher dose significantly lowered heart rate. There was no tolerance to these cardiovascular effects which were maintained up to the seventh day of clonidine infusion. The only clonidine-induced change in central monoaminergic function was an increase in the adrenaline levels in the hindbrain. No other changes in central monoaminergic function in either cortex or hindbrain were detected at the level of the enzymes (tyrosine hydroxylase) of the neurotransmitters (noradrenaline, dopamine) or of the adrenoceptors [( 3H]clonidine binding). Our results suggest that clonidine lowers blood pressure via inhibition of release of hindbrain adrenaline.

Animals↗
PubMed1984

Receptor blockade as a mechanism of deactivation of human neutrophils by pepstatin and formyl-Met-Leu-Phe.

The pentapeptide pepstatin was shown to be chemotactic for human neutrophils by two techniques: ED50 for chemotaxis was found to be 3 microM by the agarose method and 0.2 microM by the Boyden chamber technique. Pepstatin also induced superoxide radical generation, release of lysosomal enzymes, and a transient increase in intercellular adenosine-3',5'-cyclic monophosphate (cAMP) levels in a dose-dependent manner. Carbobenzoxy-phenylalanyl-methionine (CBZ-PM), which competitively inhibits formyl-methionyl-leucyl-phenylalanine (FMLP) -induced neutrophil functions, also inhibited pepstatin-induced neutrophil function of superoxide generation in a dose-dependent fashion. Likewise, pepstatin inhibited the binding of [3H]FMLP to the cells. Furthermore, preincubation of neutrophils with suboptimal concentrations of FMLP or pepstatin diminished the cellular response toward either factor when tested for their chemotactic activity and for their ability to induce superoxide generation, to release granule enzymes, and to induce a transient increase in intracellular cAMP levels. The concentrations of pepstatin or FMLP tested had no effect on superoxide generation, granule enzyme release, or intracellular levels of cAMP on subsequent challenge with C5a; both of these factors, however, cross-deactivated the chemotactic response of the cells towards C5a. Similar results were observed when cells were preincubated with C5a and subsequently challenged with pepstatin or FMLP. These results suggest that FMLP and pepstatin interact with the same receptor molecules to activate human neutrophil functions. Furthermore, our data indicate that the deactivation of the neutrophil functions of superoxide production and granule enzyme release are receptor specific, but the heterologous deactivation of chemotaxis involves a postreceptor mechanism(s).

Binding, Competitive↗
PubMed1984

Screening for refractive errors in 6-9 month old infants by photorefraction.

The method of isotropic photorefraction has been used in a trial of refractive screening of 6-9 month old infants. Data are presented on the calibration of the method against retinoscopic measurements and its reliability. In photorefractive screening of 1096 infants under cyclopentolate cycloplegia 5% were found to be hypermetropic (over +3.5 D), 4.5% myopic, and 1.3% anisometropic (over 1 D). These refractive errors were confirmed on retinoscopic follow-up (with the exception of a few anisometropes). Follow-up of controls shows that one small refractive error was missed in 52 infants. We conclude that photorefraction is a valid and practical screening technique. Longitudinal study of infants with refractive errors will assess the value of early detection, in particular for prediction and prevention of strabismus.

Adult↗
PubMed1984

Human visual development over the first 6 months of life. A review and a hypothesis.

The behavioural changes that occur in visual development in the first 6 months of human life are discussed in relation to the possible underlying changes in neurophysiological mechanisms, with inter-species comparisons being made when appropriate. Recent data on the developing infant's changing capacity to discriminate various stimulus attributes is considered. It appears that orientation discrimination and cortically related visual evoked potentials are present at, or soon after, birth. However, data on colour discrimination, field differences in detection tasks and control of visual attention suggest a subcortical site for control of behaviour for the first month of life. The improvements in spatial and temporal resolution depend on maturation of both peripheral and central structures in the visual pathway and so do not provide a clear distinction between cortical and subcortical function. There is clear evidence that binocular function in the cortex does not emerge until three months postnatally. A hypothesis is proposed that maturation of a number of pathways between cortex and subcortical structures underlies the observed behavioural changes starting at around 2 months of age. The initial immaturity of connections between cortex and pretectum may give rise to asymmetrical monocular OKN. Maturation of pathways from cortex to colliculus could account for improvements in convergence, allowing development of cortical binocularity, and for the developing ability to control shifts of visual attention.

Accommodation, Ocular↗
PubMed1983

The effects of screen size and eccentricity on acuity estimates in infants using preferential looking.

The study examined whether screen size (10 degrees vs 19 degrees dia.) and separation (3 degrees vs 10 degrees eccentricity of inner edges) affect the estimates of acuity obtained with 1-3 month infants tested by forced-choice preferential looking. One and 2-month infants (but not 3-month olds) showed higher acuity estimates with the larger screens. Screen separation did not significantly affect acuity estimates for any of the age groups. Possible factors underlying these results are discussed.

Fixation, Ocular↗
PubMed1983

Adrenalectomy potentiates drinking induced by renal artery constriction.

We have tested the hypothesis that the dipsogenic response to an increase in the circulating angiotensin level in the rat is mediated via release of catecholamines from the adrenal medulla. Increases in circulating angiotensin levels were induced by unilateral renal artery constriction in animals which were uninephrectomized and/or adrenalectomized, twenty four hours previously. The dipsogenic response to renal artery constriction was not attenuated by prior adrenalectomy--there was, in fact, a slight potentiation. Adrenalectomy also potentiated the dipsogenic response to injection of hypersomotic saline. We conclude that drinking following renal artery constriction is not mediated by release of catecholamines from the adrenal medulla.

Adrenal Medulla↗
PubMed1983

Vision screening and photorefraction - the relation of refractive errors to strabismus and amblyopia.

Isotropic photorefraction is a technique well suited for screening infants and young children for refractive errors. The photorefractive measurements have been empirically calibrated against retinoscopic refractions, so errors exceeding selected criteria can be identified in screening and followed up. Such a screening programme is in progress for the population of 6-9 month infants in the City of Cambridge. In 1096 infants screened 5% have been found to have large hypermetropic errors, 1.3% to show a refractive difference between the eyes (anisometropia) and less than 1% to have significant myopia or manifest strabismus. These findings were generally confirmed on retinoscopic examinations. In subsequent follow up of the large hypermetropic errors, most decline with age but a few show little or no change up to age 2 years and some show more change in one eye than the other leading to anisometropia. A trial is underway to examine whether early correction with spectacles can reduce the later incidence of strabismus and amblyopia in hypermetropic infants. Significant astigmatism is found in a large fraction of the infant population; the predominant axis of this astigmatism shows marked and unexplained variations between different locations in England.

Amblyopia↗
PubMed1983

Some recent findings on the development of human binocularity: a review.

Evidence on the development of binocular function in infancy is reviewed. (1) Visual evoked potentials (VEP) may be recorded from infants in response to dynamic random dot stimuli which alternate between positive and negative binocular correlation. Such responses can only arise in neurones receiving binocular input. (2) Infants' looking behaviour may be shown to depend on the presence of binocular disparity in the stimulus (either random-dot or line stereograms). Results of these techniques agree that binocular function normally develops initially between 2 and 4 months of age. Our own data using VEP show a median age of first binocular response of 13 weeks but with marked individual variations. Binocular development involves the interplay of sensory interaction and oculomotor coordination, but it is unlikely that alignment of the two eyes is the dominant constraint determining the onset of binocular vision. It is possible, but not yet established, that the detection of binocular correlation may precede the ability to discriminate stereoscopic disparities. Infants in the first 3 months of life show an asymmetry of monocular optokinetic nystagmus (MOKN). The response to temporalwards field motion which they lack is driven in cat by a pathway via binocular cortex: thus the development of this response in human infants might depend on development of binocularity. However, the correlation across individual infants between the age of onset of binocularity and the age at which symmetrical MOKN is attained is relatively weak. It is possible that the neuroanatomical basis of MOKN control differs between cat and human.

Child Development↗
PubMed1983

Reaching for rattles: a preliminary study of contrast sensitivity in 7-10 month old infants.

Contrast sensitivity for a 3 cycles deg-1 sinusoidal grating in 7-10 month old infants was tested by presenting gratings and uniform fields on cylinders, with the former providing auditory reinforcement when the infant picked them up. The method shows that a contrast as low as 7.5% can commonly be detected at this age, compared with 1-2% for adults under comparable conditions. However, as the development of hand preferences with the task as an indicator of visual sensitivity, it is concluded that this method is not in its present form suitable for vision testing on a wide scale or in a clinical setting.

Discrimination Learning↗
PubMed1983

Assessment of visual acuity in infancy and early childhood.

The forced-choice preferential looking method (FPL) shows the development of acuity during the first year of life, and is applicable to clinical assessment. A tracking test using a narrow strip of grating yields a more sensitive measure for the later part of this age range, however. The development of acuity is dominated by neural rather than optical or accommodative factors. By age 3 years resolution acuity is very close to adult performance, but at 5 years 'crowding' effects may still impair performance on practical acuity tasks more than for the adult.

Adult↗
PubMed1983

The development of binocular function in infancy.

Binocular function in infancy can be assessed by means of the visual evoked potential (VEP) induced by a dynamic random dot pattern which alternates between a binocularly correlated and an anticorrelated state. A VEP time-locked to the alternation can only be produced by binocular interaction in the cortex. This interaction becomes detectable at around three months of age. Optokinetic nystagmus (OKN) in monocular viewing becomes symmetrical in nasal and temporal directions around the same age. Animal analogues and clinical cases suggest that this may also be an indicator of cortical binocularity. These techniques may be applicable to clinical assessment of binocular function in young infants.

Animals↗
PubMed1983

The use of isotropic photorefraction for vision screening in infants.

Isotropic photorefraction is a technique which makes possible the rapid, economic, large scale screening of infants and young children for refractive errors. The relative size of blur circles reflected from the fundus in 3 flash photographs with different camera settings allows the size and direction of refractive errors to be estimated. The method has been validated against retinoscopic measures on a large group of infants. Findings of a high incidence of astigmatism in the first year are confirmed. Detection of hypermetropia in early infancy by this screening procedure may allow preventive treatment for accommodative strabismus.

Astigmatism↗