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Biomedical subjects

W N Charman

Publications and source records attributed to W N Charman.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of the mass balance assumption with respect to the two-resistance model of intestinal absorption by using in situ single-pass intestinal perfusion of theophylline in rats.

Methods of analyzing drug absorption data from rat intestinal-perfusion experiments are discussed in terms of mass-transfer resistances, or reciprocal permeabilities, and mass balances. Typically, a two-resistance model is used to determine the dimensionless effective permeability (P*eff) by measuring the disappearance of drug from the perfusing solution. Unstated assumptions in two-resistance models are (1) the portal blood is under sink conditions and (2) complete transfer of drug occurs from the intestinal perfusate to the portal vein. The assumption of sink conditions is generally acceptable, because the drug concentration in portal blood is approximately two orders of magnitude less than in the perfusate. Single-pass intestinal-perfusion experiments were performed on rats with theophylline as a model compound. The drug mass leaving the intestinal perfusate was substantially less than the drug mass appearing in the portal plasma; that is, the assumption of complete transfer did not hold for theophylline in this experimental system. These data indicate that models based on the two-resistance theory can lead to overestimation of P*eff by the ratio of the drug mass leaving the perfusate to the drug mass appearing in the plasma. For compounds for which the assumption of complete transfer does not hold, a more accurate estimate of P*eff may be determined by dividing the value derived from perfusate data by the mass balance ratio (i.e., the drug mass leaving the perfusate divided by the drug mass appearing in the plasma).

Animals↗
PubMed1992

Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compound.

Self-emulsifying drug delivery systems (SEDDSs) represent a possible alternative to traditional oral formulations of lipophilic compounds. In the present study, a lipophilic compound, WIN 54954, was formulated in a medium chain triglyceride oil/nonionic surfactant mixture which exhibited self-emulsification under conditions of gentle agitation in an aqueous medium. The efficiency of emulsification was studied using a laser diffraction sizer to determine particle size distributions of the resultant emulsions. An optimized formulation which consisted of 25% (w/w) surfactant, 40% (w/w) oil, and 35% (w/w) WIN 54954 emulsified rapidly with gentle agitation in 0.1 N HCl (37 degrees C), producing dispersions with mean droplet diameters of less than 3 microns. The self-emulsifying preparation was compared to a polyethylene glycol 600 (PEG 600) solution formulation by administering each as prefilled soft gelatin capsules to fasted beagle dogs in a parallel crossover study. Pharmacokinetic parameters were determined and the absolute bioavailability of the drug was calculated by comparison to an i.v. injection. The SEDDS improved the reproducibility of the plasma profile in terms of the maximum plasma concentration (Cmax) and the time to reach the maximum concentration (tmax). There was no significant difference in the absolute bioavailability of WIN 54954 from either the SEDDS or the PEG formulations.

Administration, Oral↗
PubMed1992

Time-averaged accommodation response to flickering stimuli.

Experiments are described in which the steady-state accommodation response versus stimulus curve was measured with an infrared autorefractor for high-contrast stimuli having a 100% square-wave temporal modulation of luminance in the frequency band 1-200 Hz. Slightly more accurate responses were found at frequencies approximately 50-100 Hz, i.e. above flicker fusion. The relevance of the results to practical situations in which flicker may be experienced is discussed.

Accommodation, Ocular↗
PubMed1992

Effects of monochromatic and chromatic oblique aberrations on visual performance during spectacle lens wear.

An optical system is described which allows overall visual performance to be studied when the wearer of a spectacle lens views objects through the lens periphery. Performance with lenses of any refractive power can be explored without any need for subjects to have the appropriate complementary refractive errors. In comparison with the effects of dioptric defocus, transverse chromatic aberration (TCA) is found to cause a relatively greater degradation in contrast sensitivity at high spatial frequencies when tangentially-oriented gratings are observed. The relative importance of TCA appears to have been underestimated in some previous studies. As vision is found to be affected by both TCA and defocus, a careful compromise between chromatic and monochromatic aberrations is required.

Adult↗
PubMed1992

Variation in ocular modulation and phase transfer functions with grating orientation.

For circular pupils of diameters < or = 2 mm the optical performance of the eye in monochromatic light is effectively diffraction-limited, so that its modulation transfer function (MTF) is essentially independent of grating orientation and its phase transfer function (PTF) is close to zero. For larger pupils, however, the wave aberration of the eye usually exceeds the Rayleigh quarter-wavelength limit. It is shown that the monochromatic MTF may then display marked variation with orientation and the associated PTFs can be non-zero. The exact effects vary markedly with the individual subject. In white light additional asymmetries may occur due to transverse chromatic aberration.

Contrast Sensitivity↗
PubMed1992

Dynamic retinoscopy and accommodation.

The added positive lens power required for low and high neutrals at a distance of 1/3 m is determined as a function of age for a sample of 221 clinically normal subjects, aged between 10 and 80 years. These dynamic retinoscopy results are compared with corresponding laser optometer measurements of the levels of accommodation under each condition. Dark focus (tonic accommodation) measurements are carried out on a further sample of 58 subjects. Although the mean results of dynamic retinoscopy agree with those found by earlier authors, on the basis of our sample it is concluded that the considerable scatter in neutral values found in normal subjects at any age limits the usefulness of the technique as an indication of abnormality in near responses. Much of this scatter in pre-presbyopic subjects appears to be related to individual variation in the level of tonic accommodation, although near phoria may also play some role.

Accommodation, Ocular↗
PubMed1991

Self-association of nicotinamide in aqueous solution: mass transport, freezing-point depression, and partition coefficient studies.

The steady-state flux (SSF) of nicotinamide from an aqueous donor phase across a model Silastic membrane did not increase proportionally with increasing donor phase concentration. The suspected self-association of the drug in aqueous solution was evaluated by studying the concentration-dependent changes in (i) the molal osmotic coefficient of nicotinamide (freezing-point depression studies) and (ii) the partition coefficient between water and n-octanol. The freezing points of aqueous solutions of nicotinamide were measured and a plot of osmolality vs molality was nonlinear. The partition coefficient of nicotinamide, studied at 15, 25, and 32 degrees C, also decreased with increasing concentration of drug. Mathematical models describing dimerization and higher orders of association were applied to the data. The results indicated the involvement of higher orders of association and it was found that an isodesmic (step-association) model was an adequate description of the freezing-point depression and partition coefficient data. The association constant, K, ranged between 1.59 +/- 0.02 M-1 at the freezing point and 0.48 +/- 0.01 M-1 as estimated from the partition coefficient data at 32 degrees C. These models for the self-association of nicotinamide allowed estimation of the apparent concentration of "monomeric" nicotinamide in the donor phase solutions studied in the SSF experiments. When the SSF data were analyzed with regard to the concentration of monomeric nicotinamide in the donor phase, a relationship close to linearity was observed.

Administration, Cutaneous↗
PubMed1991

Wavefront aberration of the eye: a review.

The concept of monochromatic wavefront aberration is discussed in relation to ray aberration, and methods for its measurement in the case of the eye are described. Examples are given of the measured aberration in individual eyes: in general the aberration falls within the Rayleigh quarter-wavelength criterion for pupil diameters less than 2 to 3 mm but significantly degrades image quality for larger pupils. The use of wavefront data to explore both the modulation and phase transfer functions of the eye as a function of pupil diameter and focus is described, together with typical results. Potential applications to clinical problems such as the effects of contact lenses, intraocular implants, refractive surgery, and pathology on the optical quality of the eye are outlined.

Eye↗
PubMed1991

Presystemic acetylation of platelets by aspirin: reduction in rate of drug delivery to improve biochemical selectivity for thromboxane A2.

The utility of aspirin in the treatment of vascular occlusive disease has been ascribed to its blockade of platelet thromboxane A2 (TxA2), a potent inhibitor of vascular smooth muscle contraction and platelet aggregation. Coincident with the inhibition of TxA2 by aspirin at currently used dose regimens is a decrease in formation of prostacyclin (PGI2), an eicosanoid with opposing effects to TxA2 in vivo. The coincident inhibition of PGI2 could potentially limit the therapeutic efficacy of aspirin. This study addressed the issue as to whether a reduction in the rate of drug delivery could enhance the biochemical selectivity of aspirin toward inhibition of TxA2. Intubation studies were performed in parallel groups of healthy volunteers in which a 50-mg aspirin dose was administered as either a bolus or a 5 or 10 mg/hr infusion via a nasogastric tube. A control group received buffer solution. Systemic plasma levels of aspirin, major urinary metabolites of TxA2 and PGI2 and serum thromboxane B2 levels ex vivo were evaluated. Relative to the group receiving bolus aspirin, the slower rates of aspirin delivery increased the effective selectivity of the administered aspirin for TxA2. To investigate further this apparent selectivity, controlled release (CR) dose forms of aspirin were prepared and evaluated in a preliminary dose-ranging study in healthy subjects. The doses studied were 50 and 75 mg CR and a 75-mg aspirin solution. The CR aspirin dose forms decreased the maximal plasma concentration of aspirin relative to a bolus dose. The pharmacodynamic effects of the CR formulations were assessed via measurement of ex vivo serum thromboxane B2 formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1991

Ocular chromatic aberration and age.

The amount of longitudinal chromatic aberration in groups of younger and older subjects is compared in three separate studies, using a laser speckle optometer, Badal optometers with monochromatic illumination, and monochromatic retinoscopy. No evidence is found for any systematic change in chromatic aberration with age.

Adult↗
PubMed1991

A simple parametric model of the human ocular modulation transfer function.

The ocular modulation transfer function (MTF) has an important role in many investigations into human vision. It can be approximated by the equation MT = exp [-(SF/SFc)n], where MT, SF, SFc and n are the modulation transfer, spatial frequency, frequency constant and MTF index respectively. In a theoretical study, the parameters n and SFc were determined by a mathematical method from previously published data. A general equation was deduced expressing the MTF as a function of pupil size for diameters of 1.5-7.5 mm. For pupil diameters below 1.5 mm different equations providing MTFs as a function of pupil diameter have been produced. These are based on the assumption that for these pupil diameters diffraction and retinal scatter determine the optical degradation. The use of these models is described in studies on spatial vision, where they have widespread applications and the effects of optical degradation are frequently neglected.

Contrast Sensitivity↗
PubMed1990

The subjective sensitivity to small changes in the contrast of a suprathreshold grating.

Small periodic (0.25-40 Hz) changes in the contrast of suprathreshold, spatially sinusoidal (0.8-10.5 c/deg) grating test objects were generated on an oscilloscope screen. It was found that the minimum temporal modulation in spatial contrast which could be detected subjectively was approximately proportional to the mean contrast of the grating during the change, provided that the minimal spatial modulation of the grating was above threshold. The contrast increment threshold was dependent on both the grating spatial frequency and the temporal frequency of the modulation: for any fixed temporal frequency in the range 2-8 Hz it increased approximately linearly with spatial frequency; for fixed spatial frequency the threshold was minimal at temporal frequencies of a few Hz. The relevance of these results to the possible role of fast fluctuations in the control of accommodation response is considered.

Accommodation, Ocular↗
PubMed1990

Ocular hazards arising from depletion of the natural atmospheric ozone layer: a review.

The processes contributing to the maintenance of the natural, atmospheric, ozone layer, which screens the earth's surface from solar ultraviolet radiation at wavelengths below 300 nm, are described. The possible adverse effects of man-made chemicals such as chlorofluorocarbons (CFCs) on this layer are outlined. Consideration of the flux of ultraviolet light reaching the earth's surface as a function of the ozone concentration and other factors allows the effect of ozone changes on ocular health to be evaluated. It is concluded that the changes of the order of a few per cent that are predicted by current models of the atmosphere, and which are comparable with natural fluctuations in ozone, would have relatively little effect on the incidence of solar keratitis at the cornea. Larger changes, in the order of 50%, would be expected to have a significant effect. There might also be an increase in the incidence of brunescent cataract. Ozone changes would have a negligible effect on the amounts of solar radiation reaching the retina.

Cataract↗
PubMed1979

Speckle movement in laser refraction. I. Theory.

Slowly rotating, cylindrical, diffusing drums have been widely used in laser refraction. A simple geometrical evaluation of the optical path lengths involved is used to derive expressions for the position of the plane of stationarity and the apparent speed of speckle motion as a function of the characteristics of the illuminating wavefront, the drum, the refraction of the observer, and other system parameters. With apparatus of known characteristics, determination of the apparent speckle velocity allows calculation of the ametropia of the observer.

Humans↗
PubMed1979

Speckle motion in laser refraction. II. Experimental.

The validity of expressions for the position of the plane of stationarity, apparent speed of speckle movement, and estimated observer ametropia is examined for laser refraction, using a cylindrical drum. The agreement between theory and experiment is satisfactory. It appears unlikely, however, that methods of subjective refraction depending on estimation of speckle velocity can match the accuracy and precision of those based on rendering the plane of stationarity conjugate with the observer's retina. Even with experienced observers, refractive values based on estimates of speckle speed showed the unsatisfactorily large standard deviation of approximately 0.5 D.S.

Humans↗