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Biomedical subjects

R D Robinson

Publications and source records attributed to R D Robinson.

At least 19 recordsLinked to original sources
PubMed1992

Ocular pharmacokinetics of saperconazole in rabbits. A potential agent against keratomycoses.

The ocular pharmacokinetics of saperconazole, an experimental lipophilic triazole with activity against filamentous fungi, including Aspergillus and Candida species, were evaluated in rabbits by radioassay. The drug was administered by topical, subconjunctival, and oral routes. Following a single 20-microL drop of 0.25% saperconazole in normal corneas, a mean (+/- SEM) peak level of 2.32 +/- 0.06 micrograms/g was achieved in 10 minutes. In débrided corneas, a peak level of 13.09 +/- 2.87 micrograms/g was achieved in 2 minutes. The drug was rapidly cleared from the cornea within 2 hours. The administration of 13 drops during 1 hour resulted in a threefold increase in normal corneal levels and in a sixfold increase in débrided cornea levels. Peak levels following subconjunctival injection in normal corneas (12.91 +/- 2.02 micrograms/g) were approximately twofold greater than those following sustained topical administration (6.19 +/- 0.16 micrograms/g) and, in débrided corneas, were a third higher than those following topical therapy in débrided corneas. Clearance was virtually complete by 8 hours. Levels following oral administration were low and probably subtherapeutic in all ocular tissues that were evaluated. Bioassay studies revealed that 44.17% of the drug in the cornea following topical administration was bioactive.

Administration, Oral↗
PubMed1992

The evaluation of therapeutic responses in experimental keratomycosis.

Two different measures of response to therapy were evaluated in a model of keratitis caused by Aspergillus fumigatus in Dutch-belted rabbits. Combined pre and post-inoculation treatment with oral fluconazole 37.5 mg/kg bid or itraconazole 40 mg/kg bid was compared to post-inoculation treatment only and untreated controls using a standardized clinical disease severity score and quantitative isolate recovery techniques. For both drugs, there was no difference in isolate recovery rates among all three groups. However, a significant improvement in clinical disease was noted in the pre and post-inoculation treatment group compared to controls (p less than .01) and to the post-inoculation group (p less than .05) for fluconazole. A similar trend, though not statistically significant, was apparent with itraconazole treatment. This disparity highlights the difficulties associated with measuring responses to therapy in keratomycosis and emphasizes the need for more sensitive and specific measures.

Administration, Oral↗
PubMed1991

Anomalous effect of subconjunctival miconazole on Candida albicans keratitis in rabbits.

After intrastromal injection of a standardized inoculum of Candida albicans blastoconidia in Dutch-belted rabbits, the efficacy of subconjunctival therapy with amphotericin B and miconazole was evaluated using a quantitative isolate recovery technique. The subconjunctival injection of miconazole resulted in the recovery of significantly more viable organisms compared to the number recovered in controls (2,000 micrograms daily, P less than .02; 3,000 micrograms daily, P less than .01, respectively). Amphotericin B, in contrast, in dosages of 500 or 1,500 micrograms daily, had a significant therapeutic effect (P less than .03). The anomalous response to subconjunctival therapy with miconazole seen in this model suggests an effect on host defense mechanisms.

Amphotericin B↗
PubMed1991

Influence of corticosteroid on experimentally induced keratomycosis.

To assess the effect of corticosteroid on the establishment of experimentally induced keratomycoses, rabbits were injected subconjunctivally with triamcinolone acetonide on two successive days before inoculation with Candida albicans, Aspergillus fumigatus, or Fusarium solanae. Whereas isolate recovery rates declined steadily in normal control corneas, they remained stable over 15 days in corticosteroid-treated corneas. Clinically, inflammation was equivalent (A fumigatus and F solanae) or significantly less (C albicans; P = .001) until the 10th day. At 15 days, inflammation in corticosteroid-treated corneas was significantly worse in animals infected with A fumigatus (P = .003) or F solanae (P = .02). Inflammatory signs correlated inconsistently with isolate recovery. Pathogenicity of the infecting organism appears to be important in determining the degree to which corticosteroid is able to mask clinical signs of infection while enhancing fungal replication.

Animals↗
PubMed1991

DNA slit-scan flow cytometry of bladder irrigation specimens and the importance of recognizing urothelial cells.

DNA slit-scan flow cytometry was used to analyze 150 bladder irrigation specimens from 83 patients. Specimens were categorized into groups based on cystoscopy, histology, and cytopathology. Cells were stained for DNA with propidium iodide using a whole cell protocol. Non-specific fluorescence in the cytoplasm of some urothelial cells together with differential DNA staining of cell types in certain specimens was noted. DNA frequency distributions were analyzed using a semi-automated technique. Data were gated using slit-scan morphological features to remove cellular debris, multiple nuclei, and cells exhibiting nonspecific cytoplasmic fluorescence. Specimens were classified abnormal if they were aneuploid or had a hyperdiploid fraction (HDF) greater than 8%. The sensitivity to abnormality was 89% for grade 3 transitional cell carcinoma (TCC), 70% for grade 2 TCC, and 67% for grade 1 TCC. Specificity was 61%. Specimen data were then reprocessed using slit-scan morphological features to enrich for urothelial cells. The urothelial cells were identified by the ratio of nuclear diameter to cell diameter. This method was found to be in good agreement with immunofluorescent labeling of urothelial cells using the urothelium-selective T16 monoclonal antibody. The sensitivity to abnormality remained 89% for grade 3 TCC and 70% for grade 2 TCC, but fell to 52% for grade 1 TCC. Specificity for the urothelial cell enriched data increased to 77%. Reprocessing of data to enrich for urothelial elements resulted in 16 fewer specimens with an aneuploid DNA distribution and 2 fewer specimens with increased HDF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1991

An evaluation of intrastromal injection of antifungal agents.

The effect of the intrastromal injection of a mixture of amphotericin B, miconazole, natamycin, and nystatin and the component agents alone was studied in Dutch-belted rabbits by standard bioassay. Twenty-four hours following injection, the inhibiting effect of the mixture was equivalent to that of nystatin alone. All other agents exhibited inferior activity. The intrastromal injection of this mixture appears to offer no therapeutic advantage.

Amphotericin B↗
PubMed1991

Toxicity and pharmacokinetics of subconjunctival amphotericin B. An experimental study.

The pharmacokinetics and toxicity of subconjunctival (S/C) amphotericin B (AmB) were evaluated in Dutch-belted rabbits. Following the S/C injection of 1,500 micrograms of AmB, corneal and aqueous levels were determined by bioassay. The highest levels were present in the periphery of debrided corneas at 1 h (90.12 +/- 2.4 micrograms/g). The debrided central cornea contained 30.84 micrograms/g, almost double the amount present in the intact central cornea. These levels were transient; in the central intact cornea only 2.08 micrograms/g could be detected at 2 h. Peak aqueous levels were low (0.95 +/- .24 micrograms/mL in debrided corneas at 1 h). The S/C injection of 1,500 micrograms of AmB in sodium deoxycholate produced a severe inflammatory response in the conjunctiva, episclera, iris, anterior chamber, and superior rectus muscle that persisted 10 days. Injection of sodium deoxycholate alone produced a similar but less severe response.

Amphotericin B↗
PubMed1991

Gastrointestinal parasitic infection in healthy Jamaican carriers of HTLV-I.

A subsample (1.6%; n = 13,260) of a healthy Jamaican population of food-handlers, studied by Murphy et al. (1991), who were serologically positive (n = 99) or negative (n = 113) for HTLV-I was investigated for intestinal parasitic infection using coprological methods. Helminth infection included Ascaris lumbricoides (2.8%), Trichuris trichiura (7.1%) and hookworms (6.1%). Entamoeba coli was found in 21.8% of samples, while E. hartmanni, Giardia lamblia, Endolimax nana, Iodamoeba bütschlii and Chilomastix mesnili each occurred in less than 10% of responders. T. trichiura displayed a higher prevalence (10.6 vs 3%) (chi 2 = 4.623; P = 0.03) in the HTLV-I negative group. G. lamblia was detected more frequently among HTLV-I carriers compared to controls (9.1 and 3.5%, respectively), but the association was not statistically significant (chi 2 = 2.825; P = 0.09). Infection with intestinal parasites is likely to occur independent of HTLV-I status: however, possible HTLV-I-induced immunosuppression may lead to higher intensity infections of certain organisms thus facilitating easier detection using parasitological methods. The immunomodulatory potential of HTLV-I infection in the aetiology of non-malignant diseases requires further investigation.

Analysis of Variance↗
PubMed1991

The association of antiphospholipid antibodies with pregnancies complicated by fetal growth restriction.

The association of antiphospholipid antibodies with fetal growth restriction is often cited, but the published evidence for this is based on few patients and comes primarily from patient histories, not study groups. In this prospective study, we evaluated a subgroup of our population with fetuses whose estimated weights at ultrasound were at or below the tenth percentile for gestational age. Plasma and serum testing was performed to determine the presence of antiphospholipid antibodies, specifically lupus anticoagulant and anticardiolipin antibodies, respectively. From March 1990 through March 1991, 55 women were followed for suspected fetal growth restriction. Intensive monitoring of the fetal condition and modification of the mother's activity were recommended, resulting in 100% compliance. Despite this, 37 newborns were confirmed by birth weight to be at or below the tenth percentile, and all were below the 45th percentile. Fifteen of 55 women (27%) were positive for anticardiolipin antibodies, as were nine of 37 (24%) with correctly diagnosed fetal growth restriction. Five of 15 women whose newborns had ponderal indexes below the tenth percentile tested positive for anticardiolipin antibodies. None of the women had a positive lupus anticoagulant test. The prevalence of anticardiolipin antibodies in this study group was significantly higher than in our general population. We conclude that there is a statistically significant association between the presence of circulating maternal anticardiolipin antibodies and fetal growth restriction.

Autoantibodies↗
PubMed1991

Differences in response in vivo to amphotericin B among Candida albicans strains.

A group of ten Candida albicans strains previously determined to be resistant or susceptible to topical amphotericin B in vivo and in vitro were exposed to treatment with different concentrations of the drug in a quantitative model of candidal keratitis in Dutch-belted rabbits. After 5 days of topical treatment with amphotericin B eye drops in concentrations of 0.3%, 0.03%, or 0.003%, quantitative isolate recovery in treated animals was compared with that of untreated controls. A dose response was observed for all five susceptible strains. The two strains that were most sensitive to amphotericin B in vitro also were the most susceptible in vivo. At each dose level there was a two- to eightfold reduction in isolate recovery among highly susceptible strains compared with less susceptible strains (P less than 0.05). The five resistant strains remained so even when the 0.3% concentration was used. Among strains of C. albicans susceptible to amphotericin B, there appeared to be a variation in degree of susceptibility in vivo that correlated with the minimum inhibitory concentration.

Administration, Topical↗
PubMed1990

Ocular uptake of fluconazole following oral administration.

The ocular penetration and distribution of oral fluconazole was studied in Dutch-belted rabbits. Measured by high-pressure liquid chromatography, fluconazole readily penetrated all ocular tissues and fluids. No difference was observed between the levels obtained in phakic and aphakic eyes. Four hours after a single oral dose of 20 mg/kg, the mean levels and SEs were as follows: cornea, 13.3 +/- 1.4 micrograms/g; aqueous, 7.4 +/- 0.3 mg/L; vitreous, 9.8 +/- 0.9 mg/L; and choroid/retina, 5.2 +/- 0.4 micrograms/g. These levels were approximately twice those obtained with a 10-mg/kg dose. The corneal concentrations correlated highly with serum levels (r = .89). A steady accumulation in both normal corneas and corneas infected with Candida albicans was noted when 17.5 mg/kg of fluconazole was administered twice daily over a 5-day period. Drug levels did not increase in the cornea when fluconazole was administered as a single daily dose of 35 mg/kg. In view of its excellent ocular pharmacokinetic profile, fluconazole merits further attention as an orally administered agent for ocular fungal infections.

Administration, Oral↗
PubMed1990

System for acquisition and real-time processing of multidimensional slit-scan flow cytometric data.

The high-speed sampling requirements of multidimensional slit-scan signals (cell contours) have typically required custom hardware. This specialized hardware has often lacked the flexibility to adapt to varying instrument setups and experimental requirements. A hardware and software system capable of sampling multiple slit-scan cell contours at rates of up to 40 MHz with 10-bit resolution is described. It utilizes commercially available CAMAC transient recorders, a Digital Equipment Corp. PDP-11/83 computer, and custom hardware for signal conditioning and trigger generation. The modular design of the software system allows various hardware options with minimal additional coding. Real-time digital processing checks each cell contour for multiple peaks; extracts morphological features such as width, height, and area; accumulates gated histograms of these data; and optionally saves the derived data, selected contours, or both into list mode files on disk.

Cervix Uteri↗
PubMed1990

Measurements of antifungal levels in corneal tissue: a simplified bioassay for amphotericin B.

Measuring precise antifungal levels in the cornea with broth-dilution bioassays is difficult, as standard techniques involving visual determination of endpoints are hindered by corneal debris. To increase the precision of the measurement, we modified the sample preparation for bioassay of rabbit corneas treated with subconjunctival amphotericin B. Endpoint determination and variance were compared for a freshly thawed corneal suspension and the supernatant after 24 h equilibration; bioassay of the corneal suspension after 24 h equilibration served as an additional control. All endpoints were read visually in a masked fashion and were verified by culture. The three methods gave comparable endpoint values with equivalent degrees of variance. Amphotericin B levels were consistent by both visual and culture determination; however, endpoints were clearly visible and easier to read for the supernatant. Visual determination of the endpoints for the supernatant following 24 h equilibration simplified and ensured the precision of the bioassay technique.

Amphotericin B↗
PubMed1990

Inactivation of strongyloides stercoralis filariform larvae in vitro by six Jamaican plant extracts and three commercial anthelmintics.

In vitro bioassay of (a) aqueous methanol extracts (AME) of the green leaves of mimosa (Mimosa pudica), love weed (Cuscuta americana), vervine (Stachytarpheta jamaicensis), chicken weed (Salvia serotina) and breadfruit (Artocarpus altilis); (b) methanol-water fraction (MWF) of breadfruit leaves, and (c) commercially available drugs albendazole, thiabendazole and levamisole were assayed for nematode inactivating potential, using filariform larvae of Strongyloides stercoralis. Test larvae were obtained from a 10-day-old charcoal coproculture. Bioassays were conducted in Locke's solution, using 100 larvae in each of three replicates. Inactivation was recorded microscopically at 1, 3, 6 and 12 hours, then every 24 hours up to 5 days' incubation. It50 (time for inactivation of 50% of larvae) values read: levamisole and mimosa extract less than 1 hour; love weed extract, approximately 2 hours; breadfruit (MWF), 9.5 hours; chicken weed, 20 hours; albendazole, 35 hours; breadfruit (AME), 49 hours; thiabendazole, 74 hours and vervine extract, 81.5 hours. It95 values followed a similar, trend, and were approximately double the It50 measures. A potential role for locally available natural products in the treatment of strongyloidiasis is highlighted.

Animals↗
PubMed1989

Technique for cellular fluorescence distribution analysis.

The usefulness of multidimensional slit-scan flow cytometry in whole cell measurements is dependent on extracting relevant features from the cellular fluorescence distributions (slit-scan contours). In addition, the extraction of these features must be rapid to allow for real-time data processing during acquisition. This paper describes two algorithms that have been used successfully to count the numbers of local maxima (peaks) and to find nuclear boundaries in a cellular fluorescence distribution. These routines are efficient, use only simple integer arithmetic, and have been implemented on several different microprocessors.

Algorithms↗
PubMed1989

A survey of intestinal helminths of well-cared-for dogs in Jamaica, and their potential public health significance.

This study investigates the level of helminthic infestation in better-cared-for dogs in a middle-class community in suburban Kingston. A canine zoographic study was conducted, and fresh faecal deposits were collected and analysed for helminth life-cycle stages. The survey indicated that 73% (n = 93) of households in the study area owned one dog or more (mean = 1.4). Resident's attitudes towards canine management suggested that the dog population was, in general, restricted to the residential estate, and most owners claimed to have dewormed their dogs at least as young animals. Of 141 faecal specimens, 58% contained eggs or larvae of one or more of eight helminths: Uncinaria stenocephala (26%), Ancylostoma sp. (23%), Trichuris vulpis (9%), Toxocara canis (8%), Spirocerca lupi (6%), Strongyloides sp. (6%), Apophallus sp. (4%) and taeniids (1%). There was a high level of multiple infection in the host animals, with approximately one fifth of the infected samples containing three or more helminth types. Infection intensity was apparently low, but some dogs harboured heavy worm loads.

Animals↗