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J Atkinson

Publications and source records attributed to J Atkinson.

At least 145 records · Page 8Linked to original sources
PubMed1994

Modulation by the endothelium of sympathetic vasoconstriction in an in vitro preparation of the rat tail artery.

1. The influence of the endothelium on transmural electrical stimulation was investigated in isolated and perfused segments of the rat tail artery. Noradrenaline release (NA, quantified by h.p.l.c.-electrochemical detection) and changes in perfusion pressure (PP, measured at constant flow rate) were simultaneously recorded in unstimulated and stimulated arterial segments, in the absence and in the presence of drugs. The ratio PP/NA release (mmHg pg-1) was taken as an index of the noradrenergic effectiveness. 2. Removal of the endothelium produced an increase in NA release and PP, in unstimulated and stimulated arteries. This can be taken as evidence of an endothelium-derived inhibitory factor (EDIF) acting at the prejunctional level, inhibiting NA release. Furthermore, in unstimulated arteries, the ratio PP/NA release decreased suggesting the existence of an endothelium-derived contracting factor (EDCF). 3. Perfusion of arteries with N omega-nitro-L-arginine methyl ester (L-NAME, 10 microM) or methylene blue (MeB, 0.5 microM) had no effect on PP or NA release in unstimulated arteries. In stimulated arteries, both drugs potentiated the increase in PP without changing NA release and therefore, led to an increase in noradrenergic effectiveness. After removal of the endothelium, neither L-NAME nor MeB affected the increases in PP and NA release following electrical stimulation. 4. Carbachol (1 microM) attenuated both NA release and the increase in PP during electrical stimulation, and increased the ratio PP/NA release. L-NAME and MeB did not modify the inhibitory effect of carbachol on NA release, or the facilitatory effect of carbachol on the noradrenergic effectiveness. 5. Angiotensin II (All, 0.1 MicroM) potentiated the increase in PP, without modifying NA release following electrical stimulation, and facilitated the vasoconstriction induced by perfusion of NA. In the absence of endothelium, All potentiated both the increase in PP and NA release in arteries stimulated electrically but had no effect on the vasoconstriction induced by perfusion of NA. This suggests an endothelium dependent activity of All in this preparation.6. These findings suggest that, in the rat tail artery, sympathetic vasoconstriction is modulated by three endothelial factors: (1) nitric oxide (NO), the release ot which seems NA-dependent; (2) EDCF,predominant in the unstimulated state, the release of which; can be stimulated by All; and (3) EDIF,unmasked by removal of the endothelial layer, the release of which can be stimulated by All.

Angiotensin II↗
PubMed1994

Increased arterial distensibility induced by the angiotensin-converting enzyme inhibitor, lisinopril, in normotensive rats.

1. We investigated possible structural correlates of the beneficial effect of chronic angiotensin-converting enzyme inhibition (ACEI) with lisinopril on the aortic distensibility of normotensive rats. 2. Experiments were performed in young (4-month old), normotensive, Wistar rats which received lisinopril in their drinking water (0.9 or 9 mg kg-1 day-1) for 9 months. 3. Following ACEI treatment, rats were pithed and aortic pulse wave velocity was measured during the progressive rise in mean arterial blood pressure produced by i.v. infusion of the alpha 1-adrenoceptor agonist, phenylephrine. The slope of the regression line relating aortic pulse wave velocity to mean arterial blood pressure was taken as an index of aortic distensibility. Following this, the aorta was fixed in situ at a normotensive pressure level and histomorphometry was performed. We also measured the calcium content of the aortic wall by atomic absorption. 4. The lower dose of lisinopril failed to lower systolic arterial blood pressure (unanaesthetized rat) or mean arterial blood pressure (pithed rat). Chronic ACEI with the higher dose of lisinopril lowered both systolic arterial blood pressure (104 +/- 6 mmHg, controls 133 +/- 4 mmHg, unanaesthetized), and mean arterial blood pressure (27 +/- 1 mmHg, controls 34 +/- 2 mmHg, pithed). 5. Although the lower dose of lisinopril did not lower blood pressure, it did improve aortic distensibility as revealed by a fall in the slope relating aortic pulse wave velocity (Y) to mean arterial blood pressure (X). Values were 5.7 +/- 0.7, 3.8 +/- 0.6 and 2.7 +/- 0.3 in controls, and in low and high ACEI groups, respectively. 6. Lisinopril treatment did not modify the calcium content, the internal and external diameters or the medial thickness of the aorta. Chronic ACEI did, however, increase the thickness of the medial elastic fibres (controls 3.55 +/- 0.05 microm, low dose ACEI 4.05 +/- 0.15 gm (P<0.05), and high dose ACEI4.18 +/- 0.15 microm (P<0.05)).7. In conclusion, we would suggest that ACEI treatment with a low dose of lisinopril can decrease aortic stiffness via a pressure-independent mechanism which possibly involves an effect of ACEI on elastic fibres.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Reduction of endothelial function with age in the mesenteric arterial bed of the normotensive rat.

1. Age-related changes in endothelial vasodilator function were studied in an in vitro preparation of the mesenteric arterial bed removed from male, normotensive, Wistar rats. 2. Animals were killed at 2, 12 or 22 months of age, the superior mesenteric artery was cannulated and the gut removed. The mesenteric arterial bed was perfused at a constant flow rate of 4 ml min-1 and perfusion pressure was taken as an index of arteriolar tone. 3. The muscarinic agonist, carbachol, antagonized noradrenaline-induced vasoconstriction in the presence, but not in the absence, of endothelium. This cholinoceptor agonist-induced release of endothelial-derived relaxing factor (EDRF) was impaired in 22 month old rats. 4. Noradrenaline-induced vasoconstriction increased following removal of endothelium suggesting that agonist-induced release of EDRF attenuates vasoconstrictor responses to noradrenaline measured in the presence of endothelium. 5. Removal of endothelium had less effect on noradrenaline-induced vasoconstriction in old rats suggesting once again that agonist-induced release of EDRF is impaired in old rats. 6. The noradrenaline dose-response curve established in the presence of endothelium was shifted to the left in 22 month old rats. 7. In conclusion, aging in the rat appears to lead to a reduction in endothelial vasodilator function in a resistance vessel.

Aging↗
PubMed1994

Sympathetic neurotransmission in the tail artery of aging rats.

1. Age-related changes in noradrenergic neurotransmission in the tail arteries of three rat strains: outbred Wistar (WI/Ico), inbred Wistar (WAG/Rij) and inbred Fischer (F344) have been compared in the present study. 2. The arterial noradrenaline content varied from 5 to 10 ng mg-1 wet weight amongst young (3 to 6-month old) representatives of each strain, but did not change with age. As protein content increased in senescent rats (24-month old) by 30-40%, arterial tissue growth would not appear to receive a concomitant increase in sympathetic growth leading to relative, age-related, structural sympathectomy in all strains. 3. The vasoconstrictor response to transmural electrical stimulation was diminished in adult and senescent rats of all strains. 4. As far as could be judged from the increase in noradrenaline release following perfusion with the alpha-adrenoceptor antagonist, phentolamine (1 microM), the presynaptic alpha 2-adrenoceptor-mediated inhibition of noradrenaline release was intact in old representatives of all strains. 5. With blockade of the two main systems which control noradrenaline release in the rat tail artery, viz, neuronal reuptake with cocaine (4 microM) and presynaptic alpha 2-adrenoceptors with phentolamine (1 microM), stimulation-evoked release of noradrenaline was similar at all ages and in all strains. This suggests that in the rat tail artery the basic mechanism of neuronal release of noradrenaline is not functionally modified by aging. 6 We conclude that as sympathetic nerve terminals are apparently intact in all three strains of senescent rats used, the age-associated deficit of alpha-adrenergic control of vascular function is postsynaptic in nature.

Aging↗
PubMed1994

Asthma at the interface: bridging the gap between general practice and a district general hospital.

A clinic supervised by a nurse, using principles originally developed in general practice, was established in the paediatric department of a district general hospital. A randomised controlled study was conducted comparing children admitted with asthma or attending outpatients who were given a patient education programme and self management plan (intervention group) with a control group. The study comprised 91 patients aged 3-14 years admitted for asthma or attending a hospital outpatient department from November 1989 to November 1990. Seventy seven patients completed the study and kept diaries for a median of 283 days. Patients in the intervention group had significantly less restriction of activity (95% confidence interval (CI) -0.27 to -0.01) and fewer episodes of peak flow below 30% of best (95% CI 0.03 to 1.17). Patients in the intervention group were more likely to make the correct response to an acute exacerbation of their asthma than the control group (71% v 47%, 95% CI 9.51 to 39.1). The intervention group had fewer school absences and fewer home visits by a general practitioner. There was an increase in the readmission rate for the intervention group. A subgroup of patients who self managed by doubling their use of inhaled steroids during an exacerbation performed better than those patients who only increased their bronchodilator or were managed on salbutamol or sodium cromoglycate alone. Improvements in patient follow up and the structure of the self management plans used, particularly changing the peak flow level at which inhaled steroids are doubled, may further improve the outcome of patients attending the asthma clinic.

Absenteeism↗
PubMed1994

Vascular Ca overload produced by vitamin D3 plus nicotine diminishes arterial distensibility in rats.

In humans, aging produces many structural changes in blood vessels, one of the most pronounced being arterial calcium overload. Simultaneously arteries become increasingly rigid. The slow evolution of the two processes renders it difficult to evaluate the importance of vascular calcium overload in the development of decreased compliance. To gain insight into this relationship, rapid vascular calcium overload was produced by treating young rats with vitamin D3 and nicotine. When rats were allowed 16 days or longer to recover from such treatment, analysis of plasma parameters revealed no overt toxicity, and growth rate was similar to that of controls. Pronounced calcium overload was seen primarily in compliance arteries. Changes in systemic arterial compliance, characteristic impedance, pulse-wave velocity, and carotid compliance all reflected a substantial increase in arterial rigidity. Linear regression analysis revealed significant correlations between the various indicators of arterial distensibility and arterial calcium content. In conclusion, treatment of young rats with vitamin D3 and nicotine may provide a suitable model with which to investigate how calcium overload is involved in the induration of compliance arteries.

Aging↗
PubMed1994

Effect of chronic ANG I-converting enzyme inhibition on aging processes. III. Endothelial function of mesenteric arterial bed of rat.

Age-related changes in endothelial (E) function were studied in mesenteric arterial bed (MAB) preparations removed from male, normotensive, WAG/Rij rats. At the age of 6 mo, one-half of the animals was assigned to chronic treatment with a hypotensive dose of an angiotensin I (ANG I)-converting enzyme inhibitor (ACEI; perindopril, 1 mg.kg-1.day-1 po). Animals were killed at 6, 12, 24, or 30 mo of age; the MAB was perfused in vitro, perfusion pressure (PP) being taken as an index of arteriolar tone. Disruption of E function produced a fall in baseline PP in all groups except 30-mo-old rats, suggesting that 1) baseline tone is maintained by the release of E vasoconstrictor factor(s) and 2) this mechanism is impaired in 30-mo-old rats. The muscarinic agonist, carbachol, antagonized vasoconstriction produced by norepinephrine (NE) in the presence of E. This mechanism was impaired in 30-mo-old rats. NE vasoconstriction increased following disruption of E, suggesting that NE release of endothelium-derived relaxing factor attenuates vasoconstriction. This mechanism was impaired in 30-mo-old rats. Chronic ACEI postponed the age-related decrease in E function, possibly due to a direct effect, or an indirect effect via the prolonged hypotensive action of such treatment.

Aging↗
PubMed1994

Effect of chronic ANG I-converting enzyme inhibition on aging processes. IV. Cerebral blood flow regulation.

Age-related changes in systemic arterial blood pressure, basal cerebral blood flow (CBF), and CBF regulatory capacity were investigated in awake 6-, 12-, 24-, and 30-mo-old male Wistar (WAG/Rij) rats, one-half of which received the angiotensin I-converting enzyme inhibitor (ACEI) perindopril from 6 mo onward. There was no age-dependent change in mean arterial blood pressure, basal CBF, or cerebrovascular reactivity to hypercapnia, but the lower limit of CBF autoregulation rose from 70 mmHg at 6 and 12 mo to 90 mmHg in 24- and 30-mo-old animals. ACEI lowered mean arterial blood pressure but had no effect on basal CBF or on cerebrovascular reactivity to hypercapnia. ACEI shifted the lower limit of CBF autoregulation to a 20-mmHg-lower level in 12- and 24-mo animals but not in rats treated for 2 yr, i.e., from the ages of 6 to 30 mo. In conclusion, the main age-related change in CBF regulation was an increase in the lower limit of CBF autoregulation to a higher blood pressure level. Treatment with ACEI partially restored the lower limit of CBF autoregulation.

Aging↗
PubMed1993

Hemispheric asymmetries for an inspection time task: a general left hemisphere temporal advantage?

Two thematic versions of an inspection time task were administered to 18 normal, right-handed subjects. For both tasks, subjects were required to make a categorical discrimination related to the length of two lines. In one version of the task (time task), difficulty was manipulated by varying the exposure duration of the lines. In the other version (length task), difficulty was manipulated by varying the degree to which one line was shorter than the other. The time task was designed to measure the temporal acuity of the observer while the length task was used to gauge subjects' capacity for the same categorical discrimination; independent of temporal acuity. Thus, the two tasks were designed to dissociate the categorical and temporal aspects of the inspection time task. Divided visual field techniques revealed a significant left hemisphere (LH) advantage for the time task, but no asymmetry for the length task. These results could not be accounted for in terms of the categorical nature of the representation. A model, related to the LH's predisposition for the detection of fine temporal events provided a more satisfactory account of the results.

Adolescent↗
PubMed1993

Prevalence and longitudinal study of breast masses in adolescents.

This study examined the prevalence and outcome of breast masses in adolescent females and compared these teens to those without breast masses. A longitudinal study of adolescents with breast masses was conducted from October 1984 through January 1990. The prevalence of discrete breast masses in the 13-month study period was 13/400 (3.25%) among new female patients. The mean length and width of the masses were 2.8 and 1.9 cm; 86% had a solitary mass. Of 61 diagnosed with breast masses, 39 were followed for up to 40 months (mean, 7 months). Teens with a mass were older (16.8 versus 15.1 years, p < 0.001) and had a greater chance of a family history of breast disease (26% versus 10.5%, p < 0.05) than those without a breast mass. Of 39 teens returning for at least one follow-up visit, 10 had a clinical diagnosis of "fibrocystic changes." Of these, the lesions resolved in six. Of the 29 teens with a discrete mass on examination, 7 underwent surgery and were found to have fibroadenomas. Nine of the 29 teens had masses which resolved over 1-12 months, six teens had masses which remained unchanged over 3-40 months, while four had masses which became smaller, and two had masses which became larger. One teen with mastitis improved. Eighteen underwent ultrasonographic examination at the breast. Of the 12 teens found to have a solid mass on ultrasound, none had a mass that resolved on follow-up examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Intracellular free Ca2+ and vasoconstriction determined simultaneously in the perfused rat tail artery.

To measure, simultaneously, intracellular free Ca2+ ([Ca2+]i) and vasoconstriction in a perfused vessel, we used the fluorescent Ca2+ indicator fura 2 with a dual-wavelength excitation method. One-centimeter-long segments of the caudal artery were dissected from 12-mo-old male Wistar rats. The endothelium was removed by gentle rubbing. The artery was mounted in a specially constructed spectrofluorometer cuvette, perfused with oxygenated physiological saline solution at 37 degrees C, and loaded by perfusion with fura 2 acetoxymethyl ester (5 microM) over a 90-min period. This paper is a description of the technique and the experiments that validate it as a useful method for examining Ca(2+)-related vascular reactivity in an intact perfused vessel.

Animals↗
PubMed1993

In vivo cerebrovascular reactivity in Wistar and Fischer 344 rat strains during aging.

Basal cerebral blood flow (CBF) and CBF regulation after hypercapnia and hypotensive hemorrhage were investigated using H2 clearance in the frontal cortex of awake 2-, 14-, or 23-mo-old Wistar or Fischer 344 rats. Basal CBF decreased in old Wistar but not in mature Wistar (old 64.4 +/- 2.8, mature 87.6 +/- 2.6, young 79.6 +/- 2.2 ml.min-1 x 100 g-1) or in old Fischer 344 (old 71.9 +/- 2.9, young 73.3 +/- 1.6 ml.min-1 x 100 g-1) rats. Cerebrovascular reactivity to hypercapnia decreased in mature and old Wistar (old 2.1 +/- 0.3, mature 3.1 +/- 0.7, young 7.0 +/- 2.1 ml.min-1 x 100 g-1 x mmHg-1) but not in old Fischer 344 rats (old 4.6 +/- 1.4, young 4.9 +/- 0.9 ml.min-1 x 100 g-1 x mmHg-1). The lower limit of CBF autoregulation increased by 20 mmHg during maturation and/or aging in the two strains. Because blood gases and pH evolved similarly in both strains, we postulate that differences in cerebrovascular structure and/or function explain the differences in CBF regulation in the older representatives of the two strains.

Aging↗
PubMed1992

Ultradian variations in sensitivity of rat aorta rings to noradrenaline.

The in vitro sensitivity of the rat aorta to the vasoconstrictor effect of noradrenaline was found to vary according to the time the animals were killed, with a minimum at 10:00 h and a maximum at 16:00 h. This ultradian rhythm was not influenced by the presence of the endothelium but was modified by some, as yet unidentified, circulating factor(s). The results also strongly suggested an ultradian rhythm of in vitro sensitivity to the beta-adrenoceptor agonists, salbutamol and isoprenaline. This rhythm appears to be opposite to that for the sensitivity of aortic alpha-adrenoceptors to stimulation. In conclusion, our results demonstrate that the regulation of aortic tone follows an ultradian rhythm.

Animals↗
PubMed1992

Possible blindsight in infants lacking one cerebral hemisphere.

Patients with damage to the striate cortex have a subjectively blind region of the visual field, but may still be able to detect and localize targets within this region. But the relative roles in this 'blindsight' of subcortical neural systems, and of pathways to extra-striate visual areas, have been uncertain. Here we report results on two infants in whom one cerebral hemisphere, including both striate and extra-striate visual cortex, needed surgical removal in their first year. Single conspicuous targets in the half-field contralateral to the lesion could elicit fixations, implying detection and orienting by a subcortical system. In contrast, binocular optokinetic nystagmus (OKN), for which a subcortical pathway has often been thought adequate, showed a marked asymmetry. In normal neonates, fixation shifts and OKN have both been taken to reflect subcortical control; our results are consistent with subcortical control for fixation but not for OKN.

Brain↗
PubMed1992

Visual segmentation of oriented textures by infants.

The infant's visual system contains orientation-sensitive mechanisms from the first weeks of life. Differences in texture orientation can serve as a basis for rapid preattentive localization and segmentation in adults. We tested whether infants could use their orientation-sensitive mechanisms in the same way, by forced-choice preferential looking, using displays of line segments oriented at 45 degrees in a rectangular patch and 135 degrees in the surrounding region. Performance was compared with that for displays of similar elements with uniform orientation but with the patch defined by luminance contrast. Infants of 14-18 weeks old showed consistent preference for both orientation- and contrast-defined patches, indicating the ability to segment the field by orientation. Infants of 8-12 weeks performed comparably to the older infants on contrast-based segmentation but did not show a statistically significant preference with orientation-based segmentation. In a second experiment, preference was also tested for a region of mixed orientation versus a region of uniform orientation. The 14-18-week-olds did not show this preference, suggesting that their preference for the discrepant texture patch genuinely reflected texture segmentation and not simply the presence of two different orientations on one side of the display. The results are discussed in terms of the possible maturation of intracortical connections subserving texture grouping and segmentation.

Aging↗
PubMed1992

[Cerebral blood flow. Changes in regulation with aging].

In subjects without cardiovascular or neuronal diseases ageing does not seem to be accompanied by a significant fall in global cerebral blood flow at rest. Yet non-negligible changes in cerebral blood flow rate can be demonstrated by haemodynamic or metabolic stimuli. Several intra- and extracranial vascular mechanisms may be involved in these changes. During ageing, a decrease of carotid artery compliance due to parietal calcium deposition might be an important factor in the disturbance of cerebral blood flow regulatory mechanisms.

Aging↗
PubMed1992

Erythroleukemia: a review of 15 cases meeting 1985 FAB criteria and survey of the literature.

Erythroleukemia (EL) is a rare form of myelogenous leukemia the classification and definition of which has evolved over the course of its 80-year descriptive history. In 1976 the French American British (FAB) Cooperative Group included EL within the classification system of acute myelogenous leukemias as AML-M6, and agreed on a quantitative standard to be used in the diagnosis of this disorder. The standards were revised in 1985 to the form in use today. We selected a series of 15 cases from our records which specifically fit the FAB criteria for AML-M6. Extensive direct comparison between our series and the old literature is not practical because of the changes which have occurred in classification and definition of the disease. Overall we found a rough correlation between the clinical and laboratory data shown in the old literature on EL and data from our cases. These cases underscore characteristic laboratory features which correspond to what is now defined as AML-M6: these patients present with pancytopenia, frequent peripheral blood nRBCs and no, or few, peripheral blood blasts. In addition, we note the presence of a hybrid myeloid-erythroid blast in the bone marrow in this disease and suggest that this may be characteristic of this type of AML. Old literature on EL has generally shown it to be a disease of the elderly, yet we found a subset of younger patients whose clinical outcome was significantly better than that of the older patients. Finally, EL has historically been viewed as a disease in which patients progress from a prodrome through erythroleukemia to other acute myeloid leukemia (AML) subtypes. Consistent with this idea, half of our 15 patients had been previously diagnosed with myelodysplastic syndrome or received chemotherapy. On the other hand only one of the 15 patients converted to another type of AML during his course.

Adolescent↗