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Biomedical subjects

A Johnston

Publications and source records attributed to A Johnston.

At least 109 records · Page 6Linked to original sources
PubMed1997

Simple bioequivalence criteria: are they relevant to critical dose drugs? Experience gained from cyclosporine.

A critique of the current bioequivalence regulations is presented with reference to critical dose drugs. Using the development of a new cyclosporine formulation as an example, the deficiencies in current bioequivalence testing guidelines are examined and discussed. Based on the experience gained with cyclosporine, recommendations are made on how therapeutic equivalence, rather than just bioequivalence, should be established.

Area Under Curve↗
PubMed1996

Motion transparency arises from perceptual grouping: evidence from luminance and contrast modulation motion displays.

What circumstance lead to the perception of global motion transparency? it has been shown that, in paired random dot displays, motion transparency can be abolished if the separation of the dot pairs is sufficiently small. Motion transparency has also been shown to be influenced by high level cognitive cues. Here, we report that the combination of two moving dot stimuli, which separately invoke a percept of transparent motion, gives rise to a non-transparent percept of local rotation. These stimuli were constructed using various different pattern elements, including luminance defined elements and contrast modulations. The results extend and support the view that high-level grouping of local measures of the velocity field can determine whether a motion transparency is perceived or not.

Humans↗
PubMed1996

Predicting patients' exposure to cyclosporin.

The introduction of a new formulation of cyclosporin, Neoral, has reduced pharmacokinetic variability and it may be possible to simplify area-under-curve (AUC) measurements using a limited sampling strategy. We have examined the timing of blood samples necessary to obtain accurate AUC predictions for cyclosporin using limited data from stable renal transplant patients dosed twice daily with Neoral. Best subset regression of blood concentration profile data obtained from ten patients at steady state indicated that two samples, timed at 2 and 8 h post-dose, accounted for 97% of the variance in AUC. The accuracy of this prediction was tested using profile data collected in a further 36 patients on three occasions separated by 4 and 44 weeks. Using the regression, AUC = 1.96 x [2 h] + 11.5 x [8 h] + 355.2, the mean (95% CI) prediction errors of the three occasions were 1.7% (-2.1-5.4%), 3.3% (-2.6-9.2%) and 0.4% (-3.4-4.2%). Data are presented that suggest AUC monitoring with a single blood sample could be feasible in a clinical setting.

Cyclosporine↗
PubMed1996

A second-order pattern reveals separate strategies for encoding orientation in two-dimensional space and space-time.

We measured the perceived spatial orientation of the low contrast regions of contrast modulated sine gratings. Subjects make systematic errors which depend upon the carrier spatial frequency and the angle between the carrier grating and the modulation. The results for the spatial orientation task are compared with a motion domain analogue. The difference in the pattern of results for these two tasks suggests there exist separate strategies for encoding orientation in two-dimensional space and space-time.

Contrast Sensitivity↗
PubMed1996

The effect of illuminant position on perceived curvature.

In shaded scenes surface features can appear either concave or convex, depending upon the viewer's judgement about the direction of the prevailing illumination. If other curvature cues are added to the image this ambiguity can be removed. However, it is not clear to what extent, if any, illuminant position exerts an influence on the perceived magnitude of surface curvature. Subjects were presented with pairs of spherical surface patches in a curvature matching task. The patches were defined by shading and texture cues. The perceived curvature of a standard patch was measured as a function of light source position. We found a clear effect of light source position on apparent curvature. Perceived curvature decreased as light source tilt increased and as light source slant decreased. We also found that the strength of this effect is determined partly by a surface's reflectance function and partly by the relative weight of the texture cue. When a specular component was added to the stimuli, the effect of light source orientation was weakened. The weight of the texture cue was manipulated by disrupting the regular distribution of texture elements. We found an inverse relationship between the strength of the effect and the weight of the texture cue: lowering the texture cue weight resulted in an enhancement of the illuminant position effect.

Cues↗
PubMed1996

Investigating shape-from-shading illusions using solid objects.

Recent growth in the shape-from-shading psychophysics literature has been paralleled by an increasing availability of computer graphics hardware and software, to the extent that most psychophysical studies in this area now employ computer lighting algorithms. The most widely used of these algorithms in shape-from-shading psychophysics is the Phong lighting model. This model, and other shading models of its genre, produce readily interpretable images of three-dimensional scenes. However, such algorithms are only approximations of how light interacts with real objects in the natural environment. Nevertheless, the results from psychophysical experiments using these techniques have been used to infer the processes underlying the perception of shape-from-shading in natural environments. It is important to establish whether this substitution is ever valid. We report a series of experiments investigating whether two recently reported illusions seen in computer-generated, Phong shaded images occur for solid objects under real illuminants. The two illusions investigated are three-dimensional curvature contrast and the illuminant-position effect on perceived curvature. We show that both effects do occur for solid objects, and that the magnitude of these effects are equivalent regardless of whether subjects are presented with ray traced or solid objects.

Algorithms↗
PubMed1996

Three-dimensional curvature contrast--geometric or brightness illusion?

Simultaneous contrast effects have been found across a wide range of visual dimensions. We describe a simultaneous contrast effect--three-dimensional curvature contrast--in which the apparent curvature of a surface defined by shading and texture information is influenced by the curvature of a surrounding surface. The effect is strong and easily measurable. We asked whether the effect depends upon the presence of contrast at the level of the internal representation of surface curvature or whether it could be better explained in terms of local changes in the apparent brightness of regions within the test patches induced by luminance transitions at the borders. The experimental results suggest that, while these luminance-contrast-induced effects do contribute to the observed changes in perceived curvature, there are additional influences. In particular changes in perceived curvature induced by a pattern of curved patches were eliminated or considerably weakened when the inducing pattern was transformed into a photographic negative, a procedure which disrupts the apparent three-dimensional structure of the surface patches without changing their brightness contrast. This suggests a component of the illusion involves comparisons at the level of representation of surface curvature. The observation that three-dimensional curvature contrast persists when the inducing surfaces are spatially separate from the test surface suggests that shape perception involves global, as well as local, operations.

Depth Perception↗
PubMed1996

Aspartame pharmacokinetics - the effect of ageing.

Aspartame is an intense sweetener which is increasingly used in the UK. It is registered at an acceptable daily intake (ADI) of 40 mg/kg, although there are no previous data relating to the metabolism of aspartame in older people. Twelve young and 12 elderly volunteers each received a single dose of approximately 40 mg/kg of aspartame. Baseline concentrations of phenylalanine (the main metabolite of aspartame) rose after ingestion with a significantly higher maximum concentration (Cmax) (81.3 vs. 63.3 micromol/1, p<0.01) and area under the plasma concentration-time curve extrapolated to infinity AUC 9(0-infinity)(518.7 vs. 353.5 micromol . h/l, p<0.01) in the elderly group. The higher concentrations reflected a significant fall in volume of distribution (V) from 2.03 to 1.59 1/kg (p <0.05) and clearance (CL) from 7.3 to 4.9 ml/min/kg (p <0.005) in the elderly group. The greater effect on CL than on V resulted in a small but non-significant rise in elimination half life (3.5 to 3.9 hours). The sizes of the differences were modest implying that there is no need on pharmacokinetic grounds for a change in the ADI for older people.

Adult↗
PubMed1996

Mobility of people with retinitis pigmentosa as a function of vision and psychological variables.

We investigated the mobility performance of subjects with retinitis pigmentosa (RP) as a function of clinical measures of residual vision and psychological variables. We found a highly significant correlation between clinical measures of residual vision and mobility. Pelli-Robson contrast sensitivity and residual visual field together explained 64% of the variance in mobility performance in an indoor shopping mall. We suggest a simple new clinical method of scoring the visual field for predicting mobility performance, the RP Concentric Field Rating. The RP Concentric Field Rating alone explained 60% of the variance in mobility performance. In spite of expectations derived from reading the recent literature, we did not find a significant correlation between psychological variables and mobility performance in a group of subjects with RP.

Adolescent↗
PubMed1996

Quality assessment issues of new immunosuppressive drugs and experimental experience.

There are established quality assessment schemes for the two immunosuppressive drugs that have entered routine clinical use: cyclosporine and tacrolimus. These two drugs, together with sirolimus and mycophenolic acid, have been the subject of recent consensus panel reports that have reached broad agreement on several issues relating to therapeutic monitoring of these agents. While the current quality assessment schemes are not based on validated reference methods, the data they yield on comparative assay performance are of value as a guide to patient management and for clinical studies of drug efficacy.

Cyclosporine↗
PubMed1996

Foreign body in the hypopharynx--an unusual presentation.

A case is described of a foreign body (a metallic paper clip) in the hypopharynx of an 18 month old child presenting with recurrent respiratory tract infections. The child was treated with antibiotics at two accident and emergency departments without any benefit. A high degree of suspicion is necessary in young children, as a history of ingestion of a foreign body may not be forthcoming. It is important to be aware of the possibility of a foreign body in young children, particularly when the clinical presentation is atypical.

Emergencies↗
PubMed1996

Estrogens--pharmacokinetics and pharmacodynamics with special reference to vaginal administration and the new estradiol formulation--Estring.

The consequences of diminished plasma estrogens in post-menopausal women are reviewed. The various options for estrogen replacement therapy are discussed with reference to the risks and benefits of estrogen therapy. The changes in estrogen plasma concentrations and the resulting systemic actions that occur following vaginal administration of different formulations of estrogens are reviewed with reference to Estring, a new intra-vaginal formulation designed to give sustained delivery of estradiol to the vaginal mucosa. The possibility of Estring causing local, adverse, actions on the endometrium and the reasons why this is unlikely are described.

Administration, Topical↗