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Biomedical subjects

R Pritchard

Publications and source records attributed to R Pritchard.

17 recordsLinked to original sources

Clinical features of human infection with Scedosporium inflatum.

We report on 17 Australian cases of human infection or colonization with Scedosporium inflatum. The spectrum of clinical manifestations was similar to that in infection caused by Scedosporium apiospermum. The patients were classified into three groups. Four immunocompetent patients who presented with localized infections of a joint, nail bed, eye, or sphenoidal sinus made up the first group. Our first case, in a boy with posttraumatic septic arthritis, responded to surgical drainage with amphotericin B followed by treatment with itraconazole. The other three cases were cured by surgery alone. The second group consisted of five immunocompromised patients who presented with disseminated infections in a variety of sites. Four of these patients did not respond to antifungal therapy and died. The fifth apparently responded to antifungal drugs after correction of his neutropenia. The third group included eight patients with asymptomatic colonization in the external ear (five cases) or respiratory secretions (three cases). The nine isolates of S. inflatum tested by both disk and agar dilution methods were resistant to antifungal drugs. In our first case, which responded clinically to itraconazole, the MIC of this drug for the fungal isolate was 25 micrograms/mL. Thus S. inflatum can cause a broad spectrum of human infections whose severity and prognosis depend largely on the host's immune status.

Acquired Immunodeficiency Syndrome

Pharmacokinetics of norethindrone: effect of particle size.

In 24 healthy women between the ages of 19 and 35 years who had not used oral contraceptive preparations for at least 60 days, it was found that the smaller the particle size of norethindrone (NET) administered, the higher was the plasma NET level obtained. Three different preparations having particle sizes of NET smaller than 250 microns, 44 microns or 10 microns were tested in a crossover pattern. The time required to reach maximum plasma concentration (Tmax) became shorter with decreasing particle size, 1.69 hr, 1.52 hr and 1.06 hr, respectively. As particle size was reduced, the maximum NET plasma concentration (Cmax) increased for the 3 different 1 mg NET preparations, i.e. 8.66 ng/ml, 10.53 ng/ml and 15.73 ng/ml. A trial with a 2 mg NET preparation made with NET utilizing the 44 microns same material displayed a Tmax similar to the 1 mg NET preparation having the same particle size while the Cmax reached a level of 17.56 ng/ml. The area under the plasma concentration versus time curve from 0-24 hrs and the extrapolated total area under the curve, increased with decreasing particle size. The use of a smaller particle size allows for more rapid dissolution or oral contraceptive tablets when measured in vitro; however, there is no evidence that such faster dissolution leads to a significant difference in efficacy. Oral contraceptive tablets have, since their inception, utilized both large and small NET particle size material in various preparations.

Administration, Oral

Cerebral nocardiosis--clinical and pathological findings in three patients.

Cerebral nocardiosis is an uncommon but increasingly diagnosed infection in Australia. We report three cases. One occurred in an immunosuppressed male in whom the diagnosis was made at autopsy, one in an otherwise healthy elderly woman with subcutaneous nocardiosis, and the third was a posterior fossa nocardial abscess without systemic involvement occurring in a previously healthy woman after surgical excision of a meningioma. Primary cerebral nocardiosis is rare, with only two cases of primary posterior fossa nocardiosis reported. The cases highlight the difficulty of diagnosis and the need for aggressive treatment with a combined approach of surgical drainage and antibiotic therapy. The antibiotic regime of choice is the subject of controversy. Rifampicin, cephalosporins, imipenem, sulphonamides and other agents were used with varying success in our patients. Cerebral nocardiosis should be considered in any patient with a cerebral space occupying lesion.

Aged

Trigeminal neurilemoma: appearance on magnetic resonance imaging.

Neurilemomas can arise anywhere along the trigeminal nerve, and therefore can be either intra-axial or extra-axial. Small neurilemomas in Meckel's cavity may not be detectable with CT scanning because of bone artifact or normal enhancement of the cavernous sinus. We have reported two patients with trigeminal neurilemoma who were evaluated preoperatively with magnetic resonance imaging.

Adult

Effect of surfactants on percutaneous absorption of naproxen I: comparisons of rabbit, rat, and human excised skin.

The in vitro skin penetration model using excised skin from rats, rabbits, and humans was examined to evaluate the relative effect of surfactants on percutaneous absorption of naproxen. Differences in the magnitude of the effect of surfactants in promoting percutaneous absorption of naproxen through skins of different species were observed. For comparative evaluations of the formulation effects on percutaneous absorption, such as the effect of surfactants, in vitro studies with animal skin may not provide information in agreement with in vitro human skin.

Animals

Effect of surfactants on percutaneous absorption of naproxen II: in vivo and in vitro correlations in rats.

The effect of surfactants on percutaneous absorption of naproxen was studied using rat in vivo models. The in vivo normalized relative absorption rates were in good agreement with the in vitro relative flux. An antipyretic model in the rat could not show relatively small increases in percutaneous absorption caused by the surfactants. Based on these results, it is apparent that reliance on the rat, using either in vitro or in vivo models, may lead to erroneous conclusions when considering the effect of surfactants on human percutaneous absorption of drugs such as naproxen.

Animals

The use of mixtures of topical corticosteroids as a mechanism for improving total drug bioavailability: a preliminary report.

The feasibility of using mixtures of corticosteroids as a mechanism for enhancing total percutaneous absorption of drug has been investigated. The results of this study indicate that under certain conditions, mixtures of corticosteroids exhibit independent solubility, partitioning and diffusion behavior. Mixtures of three 21-esters of fluocinolone acetonide were found to penetrate excised human skin independently. The mixture flux rate was demonstrated to greatly exceed that attained with any of the component steroid esters at an equal concentration. A mixture composition containing a total steroid concentration of 0.015% was shown to produce significantly greater in vivo human vasoconstriction than any of the individual steroids at comparable concentrations. These results strongly support the potential clinical utility of certain topical corticosteroid mixture compositions.

Administration, Topical

Release of corticoids from oleaginous ointment bases containing drug in suspension.

Simplified methods for studying the release of drugs suspended in oleaginous ointment bases were developed. These procedures were used in studying the release rates of two corticoids, fluocinonide and flucloronide, from white petrolatum and petrolatum containing various adjuvants. A practical method for measuring drug solubilities was developed and used in determining solubilities of these corticoids in ointment bases. When using physical data obtained from model ointments, the release rates of drugs from modified ointment bases were predicted. Comparisons of the observed and predicted rates from ointments containing hydrophobic adjuvants indicated the usefulness of the physical model approach in predicting the release rates. For ointments containing emulsifying agents, the simple model used did not provide useful predictions.

Adrenal Cortex Hormones

Geometrical illusions and the response of neurones in the cat's visual cortex to angle patterns.

1. This report describes the responses of thirty-six single neurones in the primary visual area of the cat's neurologically isolated and unanaesthetized forebrain, to movements of thin white lines across the visual field. The experiments were designed to record the effects upon the response to a single test line of an added line, which was either parallel to the test line or joined it, making an angle-pattern of 30 degrees . Unit responses were measured in terms of the peak probability of firing derived from a post-stimulus histogram.2. All of the cortical neurones tested exhibited a preferred orientation for stimulation by the test line, i.e. an orientation of the line which produced a maximal response when the line passed through the centre of the unit's receptive field.3. There was no evidence that the orientation of a single test line preferred by cortical neurones was different from that preferred by the same cell when excited by an angle pattern, one arm of which was the original test line.4. The position of a test line (with preferred orientation) in the visual field that produced a maximal response from cortical neurones, was not always the same as the position for maximal response, when a second line was added to make either an angle pattern or to make a pattern of two parallel lines.5. Where the two lines of these patterns were close together and separated by less than the radius of the receptive field, the position for maximal response to the test line was shifted towards the added line. Where the two lines were further apart than this but separated by less than a receptive field diameter, the optimal position for the test line was displaced away from the added line.6. Some evidence was found of a lateral inhibition in the visual system, sufficient to account for the displacements described in paragraphs 4 and 5 above.7. It is concluded that the tip of an angle pattern of 30 degrees produces a distorted cortical image within the primary visual area.8. This neural distortion of sensory information seems adequate to explain the well known illusions of orientation that are associated with human perception of patterns containing acute angles.

Action Potentials

Cortical conditions for fused binocular vision.

1. The behaviour of twenty-six single neurones has been studied in the visual cerebral cortex of the cat's neurologically isolated and unanaesthetized forebrain. In a separate series of experiments binocular vision was investigated in five human subjects.2. Units in the cat's brain were excited by two straight, light-dark edges, projected independently, one upon each retina; these edges were given identical, artificial saccadic movements. The average response of neurones was measured from the post-stimulus-histogram (P.S.H.), which provided the probability of unit-discharge at various times after the pattern movement.3. A district within either eye-field could usually be found, such that the saccadic movements of edges passing through this part of the field, caused maximal responses; this part of each field is termed the ;representative district'. The most exciting orientations of the stimulating patterns were similar for both eyes. A cell excited by similarly oriented patterns, ;aligned' through the representative districts for each eye, exhibited dramatic spatial summation. Mutual inhibition between retinal inputs was never seen.4. The response of cortical neurones to such aligned patterns was always greater than that when one pattern was misaligned by displacement in either direction from its representative district.5. When the pattern in one eye was inverted, the cell gave less response to aligned than to misaligned patterns.6. Human subjects, viewing similar inverted patterns through a mirror stereoscope, could only obtain stable fusion with a 5 min arc misalignment of the optic axes.7. In other experiments, one eye of each subject was presented with a white rectangular bar upon a black background, while the other eye was excited by a similar black bar upon a white background. Stable fusion was reported, providing percepts of either one single low contrast bar or two neighbouring bars of high contrast. There was a range of relative pattern positions over which alignment of the eyes sought the former percept in preference to the high contrast pattern.8. These results are consistent with the hypothesis that the mammalian visual system maintains binocular fusion by continuously hunting those eye directions that provide the greatest local cortical responses to saccadic movements, restricted to the smallest possible areas of the visual cortex.

Animals