Effect of grapefruit juice on blood cyclosporin concentration.
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Antioxidants↗
Biomedical subjects
A Johnston
Publications and source records attributed to A Johnston.
Effect of ageing and propranolol administration on myocardial beta-adrenoceptor receptor function in mature rats.
Ageing is accompanied by diminishing myocardial tissue beta-adrenoceptor responses. The relative contribution of maturation and senescence to reported age-related changes in cell-surface beta-adrenoceptor dysfunction has not been established, since previous investigation has incorporated young rats lacking full maturity. We have examined myocardial ventricle membrane beta-adrenoceptor function in mature young (6 month) and old (26 month) male Wistar rats and the effect of propranolol infusion for seven days on beta-adrenoceptor function in these groups. beta 1-adrenoceptors comprised 63-72% of total beta-adrenoceptor density in both groups. beta 1-adrenoceptor densities were similar in young and old rats (young, 20.4 +/- 2.3; old, 24.7 +/- 1.4 fmol/mg protein +/- S.E.). beta 2-adrenoceptor densities were higher in older rats (young, 8.2 +/- 0.5, n = 9; old, 13.6 +/- 1.8, n = 9 fmol/mg protein +/- S.E., P < 0.025). Subcutaneous infusion of propranolol for seven days with miniosmotic pumps was accompanied by an increase in beta 1- and beta 2-adrenoceptor densities in young rats only (beta 1-, 38%, P < 0.05; beta 2- 52%, P < 0.025). beta 1-adrenoceptor agonist affinity and adenylate cyclase response to isoprenaline, GTP, Gpp(NH)p, Mn2+ and forskolin were not affected by age or propranolol infusion in either age-group. These findings demonstrate that male Wistar rats do not exhibit changes in myocardial ventricle beta-adrenoceptor-G-protein coupling capacity or adenylate cyclade activation with ageing beyond maturity.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Pharmacokinetics of orally administered cyclosporine in patients with Crohn's disease.
Cyclosporine pharmacokinetics were reported to be influenced in patients with Crohn's disease. To explore the relationship between Crohn's disease and cyclosporine pharmacokinetics, this investigation was performed in 20 patients with varying Crohn's Disease Activity Index (CDAI). A single oral dose of 300 mg of cyclosporine was given and serial blood samples were obtained over 52 hours. Cyclosporine whole blood concentrations were determined by a specific monoclonal radioimmunoassay. Pharmacokinetic parameters were comparable with those of healthy volunteers. No statistically significant difference between the pharmacokinetic parameters of the patients with CDAI values less than 150 and those with CDAI values 150 or greater could be shown. Although several factors associated with the pathology of Crohn's disease theoretically could influence the pharmacokinetics of orally administered cyclosporine, this investigation did not identify statistically significant differences in cyclosporine pharmacokinetics in Crohn's disease patients with different disease activities or different localization of inflammation as compared with healthy volunteers. However, if large parts of the small bowel were removed, a decrease of absorption of cyclosporine could be observed. In any case, it is important to be aware of the clinical variability of Crohn's disease and its potential implications in cyclosporine absorption.
Administration, Oral↗
PrP gene dosage and long term potentiation.
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Animals↗
Repair of congenital diaphragmatic hernia after weaning from extracorporeal membrane oxygenation.
Stabilization and delayed operation for patients with congenital diaphragmatic hernia (CDH) is now widely accepted. When preoperative extracorporeal membrane oxygenation (ECMO) is needed, most centers have CDH repaired on ECMO to minimize the risk of postoperative deterioration. The authors adopted a policy of weaning from ECMO before repair in an effort to avoid hemorrhagic risks. They reviewed their experience with CDH patients who required ECMO for stabilization before repair but for whom post-ECMO repair was planned. The records of all high-risk CDH patients with a gestational age of at least 34 weeks were reviewed. Eighteen patients were identified. None of the eight who were stabilized and operated on without ECMO required bypass postoperatively; all survived. Ten were placed on bypass, nine for stabilization before repair. Of the nine, seven (78%) were weaned from ECMO to conventional ventilation. Repair of the diaphragmatic defect was performed an average of 3.8 days later; none of these patients had severe pulmonary hypertension postoperatively, and all survived. Two could not be weaned before repair, one of whom had a complex congenital heart defect. This patient died. The other patient had repair on ECMO because of intrathoracic gastric volvulus. Severe blood loss prompted decannulation, and the patient died. One patient who was placed on bypass was transferred 10 days after having had repair elsewhere (at 4 hours of age). Pulmonary hypertension did not resolve, and the postmortem examination showed alveolar capillary dysplasia, with focal misalignment of the pulmonary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Extracorporeal Membrane Oxygenation↗
A unified account of three apparent motion illusions.
We discuss three motion illusions, the fluted square wave illusion, the reverse phi illusion and the Pantle illusion. In these illusions reversed apparent motion is either induced or eliminated by the introduction of a blank inter-frame-interval between the frames of the apparent motion sequence. In order to simulate these effects with the multi-channel gradient model we had to introduce low-pass spatial filters and second-order temporal differentiating filters. These illusions have been used as evidence of multiple motion mechanisms. Here we demonstrate that they can be considered as emergent properties of a single computational strategy.
Humans↗
Perceived motion of contrast-modulated gratings: predictions of the multi-channel gradient model and the role of full-wave rectification.
The paper examines the perception of motion in contrast-modulated sine-wave grating patterns. These non-rigid motion patterns give rise to a spatially-structured motion percept in which perceived speed varies with spatial position. We measured the perceived motion of the low contrast regions of amplitude-modulated gratings as a function of the carrier frequency, the carrier speed, the shape of the modulation signal and the modulation depth. We found that for static carriers perceived speed was greatest in the low contrast regions of the display. The speed of the low contrast regions was underestimated and perceived speed decreased as the spatial frequency of the carrier increased. When the direction of the motion of the carrier was opposite to that of the contrast modulation, the low contrast regions could appear to be stationary. The perceived speed of the contrast modulation increased with modulation depth. The brightness contrast of the carrier grating had little effect on perceived speed of contrast-modulated patterns for average contrasts of over 10%. A motion model which had full-wave rectification as an explicit pre-processing stage followed by low-pass filtering or some other selection criterion, would predict that the motion of contrast-modulated gratings should appear rigid and that the motion of the envelope should be judged correctly. The Multi-channel Gradient Model however predicts both the structured motion field experienced when viewing these second-order motion patterns and the reductions in perceived speed as a function of carrier spatial frequency and carrier speed.
Contrast Sensitivity↗
Cyclosporin A: analytical methodology and factors affecting therapeutic drug monitoring.
The majority of centres measuring cyclosporine have followed the advice of previous consensus meetings. Although most measurements are made using assays with a high specificity for the parent compound, there are still some between-method differences that can be attributed to methodological variables, such as antibody specificity and assay calibration. With experience of cyclosporine therapeutic drug monitoring (TDM) now spanning 15 years, it would be reasonable to infer that the subject is incapable of growth. However, continued interest in the pharmacokinetics of cyclosporine, the introduction of a new formulation of the drug, and the development of new immunosuppressive agents all combine to emphasise the still incomplete extent of our knowledge in this field.
Cyclosporine↗
Human discrimination of surface slant in fractal and related textured images.
Slant-discrimination thresholds were measured for textures with the property that their power spectra, when log transformed, are inversely proportional to log spatial frequency: P(f) alpha f-beta. As the exponent beta changes from high values to low values, the slope of the power spectrum of the image decreases. As the parameter passes through values in the fractal range the resulting texture changes from having the appearance of a cloud-like surface through to a granite-like surface. Exponents below the fractal range produce textures that converge towards the appearance of a random grey-level noise pattern. Since fractal patterns are self-similar at a range of scales, one might think it would be difficult to recover changes in depth in fractal images; however, slant-discrimination thresholds did not differ substantially as a function of the slope of the power spectrum. Reducing the size of the viewing aperture increased thresholds significantly, suggesting that slant discrimination benefits from a global analysis. The effect of texture regularity on perceived slant was investigated using bandpassed fractal textures. As the bandwidth of a bandpass filter is reduced, the bandpassed texture was perceived to be increasingly more slanted than its fractal counterpart.
Form Perception↗
Concentration-controlled trials. What does the future hold?
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Antineoplastic Agents↗
Hemodynamic and humoral effects at rest and after head-up tilt tests during 24-hour infusion of a new nitrate ester, ITF 296, compared with ISDN and placebo in healthy volunteers: a double-blind, randomized, within-subject study.
A double-blind, randomized, three-way complete crossover study was carried out to compare pharmacodynamic effects and tolerability during a 24-h intravenous infusion of ITF 296, isosorbide dinitrate (ISDN), and placebo, in the supine position and during 70 degrees head-up tilt. Ten healthy men aged 21-34 years participated in the study to obtain complete data in nine. Dosing started at 1 microgram/kg/min and was titrated up during the first 30 min of infusion, to produce a 10% reduction in diastolic blood pressure (DBP). At least 6 days elapsed between consecutive treatments. Heart rate (HR) and blood pressure were measured at least half hourly throughout the infusion period and up to 2 h afterwards. Systolic time intervals were measured before and at 0.5, 1, 2, 3, and 24 h of infusion in the fasting state. Tilt tests (70 degrees head-up for 2 min) were performed at 1, 6, 12, and 24 h of infusion. From 60 min before tilt, during tilt, and up to 15 min after end of tilt, ECG was monitored and BP, HR, and b/a ratio were recorded by means of fingertip plethysmography. Plasma-renin activity and concentrations of epinephrine and norepinephrine were measured preinfusion, and before and after tilt tests. Subjects were questioned frequently about adverse events. General tolerability of ISDN in the nine subjects who completed the study was poor, with eight suffering from headache and four from symptoms suggesting postural hypotension during tilt tests. Tolerability of ITF 296 was better, with 5 of 10 subjects reporting headache and 2 of 10 symptoms of postural hypotension during the first tilt only. Both active treatments successfully reduced DBP by at least 10% in all subjects at similar dose levels (final infusion rates 2.8 and 2.3 micrograms/kg/min for ITF 296 and ISDN, respectively). Systolic blood pressure (SBP) was reduced by about 6-7 mm Hg by both treatments. HR was increased by about 5 beats/min by ISDN but not by ITF 296. Those changes in BP and HR persisted throughout the 24-h infusion and reversed when it was discontinued. Fingertip plethysmography showed a profound reduction of b/a ratio, which persisted throughout the 24-h infusion. ISDN had consistently greater effects than ITF 296, suggesting that ISDN has the greater effects on small arterial vessels. Both active treatments reduced QS2 index throughout the 24-h period. Both treatments also reduced left-ventricular ejection time (LVET) index up to 3 h of infusion, with ISDN having the greater effects on LVET index and ITF 296 being intermediate between ISDN and placebo. ISDN prolonged pre-ejection period (PEP) at 1 h, had no effect at 2 h, and shortened PEP at 3 and 24 h. ITF 296 decreased PEP consistently during the 24-h infusion. Plasma-renin activity, epinephrine, and norepinephrine were increased by ISDN substantially more than by ITF 296. These results show that both ITF 296 and ISDN had comparable effects on diastolic blood pressure at similar dose-levels. ISDN increased HR, whereas ITF 296 did not. b/a Ratio was reduced more by ISDN, suggesting a greater activity on small arterial vessels. Arterial effects were maintained throughout the 24-h infusion. ISDN had a greater effect on venous return than ITF 296. ITF 296 seemed to show more balanced effects on preload and afterload than ISDN. ISDN caused significantly greater neurohumoral counter-regulation than ITF 296. Hemodynamic response to tilt was attenuated, as judged by the fact that hypotension occurred only during the early hours of the infusion, but the variability in the response of BP to tilt does not allow any firm conclusions to be drawn about possible development of tolerance. Tolerability of ISDN was poor and that of ITF 296 was better.
Adult↗
Commentary on the publication of the study by Plavsić et al., "Bioequivalence of two oral cyclosporine preparations" in Arzneim.-Forsch./Drug Res. 45 (II), No.8, p. 914-917 (1995).
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Administration, Oral↗
Cyclosporin pharmacokinetics in heart-lung transplant recipients with cystic fibrosis. Effects of pancreatic enzymes and ranitidine.
Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg.kg-1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg.kg-1). The mean maximum blood concentration of CsA for the oral dose was 776 ng.ml-1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng.ml-1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.
Administration, Oral↗
Independent encoding of surface orientation and surface curvature.
Marr [(1982) Vision, San Francisco, Calif.: Freeman] proposed that we represent surface geometry in terms of a viewer-centred description of surface orientation and distance. This description is computed by a range of independent processing systems which take as input particular kinds of information present in images, like surface texture, shading, retinal disparity and motion parallax. The outputs of these modules are integrated in order to provide a unitary representation of the layout of visible surfaces. Higher order properties of surface geometry, like surface curvature, might be computed from this symbolic representation or might be encoded independently from the visual information available at the retinae. We measured surface slant and surface curvature discrimination thresholds for surface patches defined by shading, texture and retinal disparity as a function of the elevation of the illumination. We found that observers judgements about the curvature of local surface patches were too precise to be based on a symbolic representation of surface orientation and we conclude that surface curvature is computed directly from depth cues present in the retinal images.
Depth Perception↗
Integration of shading and texture cues: testing the linear model.
One of the first attempts to develop a formal model of depth cue integration is to be found in Maloney and Landy's [(1989) Proceedings of the SPIE: Visual communications and image processing, Part 2 (pp. 1154-1163)] "human depth combination rule". They advocate that the combination of depth cues by the visual system is best described by a weighted linear model. The present experiments tested whether the linear combination rule applies to the integration of texture and shading. As would be predicted by a linear combination rule, the weight assigned to the shading cue did not vary as a function of its curvature value. However, the weight assigned to the texture cue varied systematically as a function of the curvature values of both cues. Here we describe a non-linear model which provides a better fit to the data. Redescribing the stimuli in terms of depth rather than curvature reduced the goodness of fit for all models tested. These results support the hypothesis that the locus of cue integration is a curvature map, rather than a depth map. We conclude that the linear combination rule does not generalize to the integration of shading and texture, and that for these cues it is likely that integration occurs after the recovery of surface curvature.
Cues↗
Lack of effect of interferon alpha 2a upon fluorouracil pharmacokinetics.
The disposition of 5-fluorouracil (FUra) was studied in 19 colorectal cancer patients during treatment with FUra and high-dose leucovorin (LV) with or without interferon alpha 2a (IFN-alpha). All received LV 200 mg m-2 over 2 h, then FUra 400 mg m-2 over 5 min then FUra 400 mg m-2 over 22 h, repeated on day 2, on a 14 day cycle. Nine patients also received IFN-alpha 6 MU every 48 h, starting at least 2 weeks before the study. Series of 14 blood samples were assayed for FUra by reversed-phase high-performance liquid chromatography (HPLC). Minimum Akaike information criterion estimation was used to determine the simplest effective pharmacokinetic model. This consisted of a single compartment with first-order (linear) and Michaelis-Menten (non-linear) components to drug elimination. This model gave r2 > 0.98 in 19/20 data sets. With the Michaelis constant (KM) set at 15 microM, values were derived for the volume of distribution (Vd), the maximum rate of non-linear elimination (Vmax) and the first-order elimination rate constant (K1.e). Mean (+/- s.d.) values in control (no IFN-alpha) patients were: Vd 10.4 (+/- 1.9) l m-2, Vmax 182 (+/- 59) mumol l-1 h-1 and k1.e 4.35 (+/- 0.58) h-1. No significant differences were detected in patients receiving IFN-alpha, in whom the equivalent mean values were Vd 10.0 (+/- 0.9) l m-2, Vmax 141 (+/- 27) mumol l-1 h-1 and k1.e 3.96 (+/- 0.5) h-1. Mean trapezoidal AUC0-22 h was similar in the two groups (control patients 116 microM h, IFN-alpha patients 125 microM h). No significant correlations with renal or hepatic function were detected. These results, while not inconsistent with previous reports of a reduced rate of FUra elimination at higher IFN-alpha doses, suggest that any clinical effect of this moderate dose of IFN-alpha on FUra toxicity or activity is due to modulation at target cells, not to pharmacokinetic interaction.
Adult↗
Shape from shading. I: Surface curvature and orientation.
The human visual system makes effective use of shading alone in recovering the shape of objects. Pictures of sculptures are readily interpreted--a situation where shading provides virtually the sole cue to shape. However, shading has been considered a poor cue to depth in comparison with retinal disparity and kinetic cues. Curvature discrimination thresholds were measured with the use of a surface-alignment task for a range of surface curvatures from 0.16 cm-1 to 1.06 cm-1. Weber fractions were around 0.1, demonstrating considerable precision in this task. Weber fractions did not vary substantially as a function of surface curvature. Rotation of the light source around the line of sight had no effect on curvature discrimination but rotation towards the viewer increased discrimination thresholds. In contrast, slant discrimination declined with rotation of the light-source vector towards the viewpoint. When a band-limited random grey-level texture was mapped onto the sphere, curvature discrimination thresholds increased gradually as a function of texture contrast, even though texture and shading provided consistent cues to depth. Adding texture also increased slant discrimination thresholds, demonstrating that texture can act as a source of noise in shape-from-shading tasks. The psychophysical findings have been used to evaluate whether current algorithms for shape from shading in computer vision could serve as models of human three-dimensional shape analysis and to highlight low-level intramodular interactions between depth cues. It is demonstrated that, in the case of surfaces defined by shading, curvature descriptions are primary and do not depend upon the prior encoding of surface orientation, and Koenderink's local-shape index is suggested as an alternative intermediate representation of surface shape in the human visual system.
Attention↗
Shape from shading. II. Geodesic bisection and alignment.
Pattern-acuity tasks have provided valuable information about the precision with which the visual system can make judgments about relative spatial position in two-dimensional images. However, outside the laboratory the visual system is habitually faced with the more difficult task of making positional judgments within a three-dimensional spatial environment. Thus our perceptual systems for representing surface shape also need to support the recovery of the location and disposition of features in a three-dimensional space. An investigation of the precision of three-dimensional position judgments in two spatial-judgment tasks, arc length bisection along geodesics and geodesic alignment, is reported. The spatial-judgment tasks were defined with reference to a sphere rendered by means of ray-casting techniques. The presence of shading and texture cues had no effect on discrimination thresholds in either task. Observers' constant errors were generally less than the just noticeable distance, demonstrating that the observers can perform these positional judgment tasks without substantial bias. It is argued that there is no explicit computation of arc length on the basis of shading and texture information and that surface-orientation information cannot be used as a reference in geodesic-alignment tasks. The results raise questions about the utility of a representation of surface orientation in the human visual system.
Attention↗