Hymenolepis diminuta: ultrastructural observations on complement-mediated tegumental lysis and destrobilation of 4-day-old worms in vitro.
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Animals↗
Biomedical subjects
R D Robinson
Publications and source records attributed to R D Robinson.
An outbreak of Candida parapsilosis endophthalmitis: analysis of strains by enzyme profile and antifungal susceptibility.
Twenty-two isolates from patients with postsurgical endophthalmitis due to infection with Candida parapsilosis as a result of exposure to a contaminated ocular irrigating solution were classified by enzyme profile analysis and antifungal susceptibility. These isolates were identical to a single isolate obtained from a contaminated vial but could be differentiated, on the basis of enzyme profile and antifungal susceptibility, from randomly selected stock isolates. The combination of these tests appears to have value in discriminating epidemic from non-epidemic strains.
Amphotericin B↗
The influence of yeast growth phase in vivo on the efficacy of topical polyenes.
We compared the efficacy of two polyenes, amphotericin B and natamycin, in two models of yeast infection. In one, treatment was begun immediately after inoculation, in the other it was delayed 24 hours. In each model infection with Candida albicans was established in the corneal stroma of dutch-belted rabbits and treated topically with 5% natamycin or amphotericin B 0.15% and 0.075%. Quantitative isolate recovery techniques were used to assess response after 5 days of treatment. A significant therapeutic effect was present for amphotericin B in both models. However, delayed treatment with natamycin was ineffective using treatment schedules efficacious when begun 1 hour after inoculation. A therapeutic effect was present only with administration of the drug every 1/2 hr. This altered response may reflect a difference in susceptibility between different growth phases in yeasts.
Administration, Topical↗
Correlation of in vitro and in vivo susceptibility of Candida albicans to amphotericin B and natamycin.
The efficacy of topical 0.15% amphotericin B and 5% natamycin was examined in a model of Candida keratitis in rabbits and correlated with three tests of in vitro susceptibility: tube dilution minimal inhibitory concentration (MIC), minimal fungicidal concentration (MFC) and agar diffusion zones of inhibition. For a panel of 17 strains, the MIC classified precisely the same strains as resistant or susceptible to amphotericin B as did the in vivo response. Several strains were misclassified using the MFC and the zone of inhibition. For natamycin the MIC misclassified two strains but it was still superior to the other two tests. For all strains, amphotericin B was equal or superior in efficacy to natamycin in vivo. The tube dilution MIC for amphotericin B was a reliable indicator for natamycin efficacy in vivo.
Amphotericin B↗
In vitro and in vivo susceptibility of Candida keratitis to topical polyenes.
The susceptibility of Candida albicans to topical amphotericin B and natamycin was evaluated in a model of stromal keratitis in Dutch-belted rabbits and compared with minimal inhibitory concentrations in vitro. Treatment was delayed 24 hr to allow invasive disease to occur and was then continued for 5 days. Ten strains of Candida albicans comprised the test panel. For amphotericin B, the minimal inhibitory concentration (MIC) by tube dilution classified the same strains as resistant or susceptible as did the in vivo response. A dose-response was observed with different concentrations of the drug. For natamycin, the MIC misclassified two strains. The rate of administration of natamycin required in this model was much higher than for amphotericin B, a therapeutic effect being observed with natamycin only when the drug was administered every 30 min during the in vivo efficacy and in vitro susceptibility with these strains is in agreement with that observed in the authors' previous studies using a model of immediate treatment.
Administration, Topical↗
A statistical analysis of prescreening alarms in a population of normal and abnormal gynecologic specimens.
A multidimensional slit-scan flow system has been developed to serve as an automated prescreening instrument for gynecological cytology. Specimens are classified abnormal based on the number of cells having elevated nuclear fluorescence (alarms). An alarm region in a bivariate histogram of nuclear fluorescence versus nuclear-to-cell-diameter ratio is defined. Alarm region probability arrays are calculated to estimate the probability that an alarm falling in a particular bin of the alarm region is either from a normal or an abnormal specimen. From these arrays, a weighted alarm index is generated. In addition, summary indices are derived that measure how the distribution of alarms in each specimen compares with the average distributions for the normal and abnormal specimen populations. These indices together with current features are evaluated with respect to their utility in specimen classification using a nonparametric classification technique known as recursive partitioning. Resulting classification trees are presented that suggest information in the distribution of alarms in the bivariate histogram. In addition, they validate the features and rules currently used for specimen classification. Recursive partitioning appears to be useful for multivariate classification and is seen as a promising technique for other applications.
Cytodiagnosis↗
Multidimensional slit-scan detection of bladder cancer. Preliminary clinical results.
A multidimensional slit-scan flow system was developed for the automated recognition of abnormal cells derived from cancer of the uterine cervix and its precursors. It provides great sensitivity in both its ability to recognize cellular abnormality and to deal with the myriad potential causes of false alarms in an automated flow system. While its initial application was the automated recognition of the spectrum of neoplasia in gynecologic cytology samples, a preliminary study was carried out using specimens obtained from the urinary bladder. Cellular material was collected by bladder irrigation and stained with the fluorochrome acridine orange. One hundred fifty-three bladder irrigation specimens, including 115 abnormal specimens containing cells derived from neoplastic lesions of the bladder epithelium, were analyzed. For the purposes of this study, abnormal specimens from the urinary bladder included specimens containing cells derived from the following lesions of the urothelium: dysplasia (atypical hyperplasia), carcinoma-in-situ, and transitional cell carcinoma, grades 1-3. Approximately 50,000 cells were analyzed for most specimens. Of the 38 presumed normal specimens (specimens containing only normal urothelial components), four were instrument classified abnormal. For the 69 specimens containing cells derived from transitional cell carcinoma, grade 1, 1-2, 2, 66 were correctly classified as abnormal while three were classified as normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Carcinoma in Situ↗
Bioavailability and penetration of topical amphotericin B in the anterior segment of the rabbit eye.
The penetration of topical amphotericin B was studied in Dutch-belted rabbits using bioassay and radioassay techniques. Seven percent of total amphotericin B in the corneas, as measured by recovered 14-C, and 5% in the aqueous was in a bioactive form. Drug was not detectable by bioassay after single drop administration but after a loading dose approach, drug was present in therapeutic amounts. In inflamed corneas, a pass-through effect was noted with higher levels initially but rapid fall-off subsequently.
Administration, Topical↗
Corneal penetration of topical amphotericin B and natamycin.
The corneal uptake and penetration of 14C-labelled 0.15% amphotericin B and 5% natamycin were studied in Dutch-belted rabbits. Corneal levels of natamycin were substantially higher than amphotericin B. For both drugs, these levels were influenced by corneal contact time. In corneas debrided of epithelium, both agents entered the corneal stroma and levels were detected in aqueous in the therapeutic range. However, in corneas with intact epithelium, penetration was negligible for amphotericin B (0.23 microgram/gm at 2 mins). By contrast, although penetration of natamycin was greatly reduced, 7.0 micrograms/gm were present at 2 mins.
Administration, Topical↗
The Indiana Living Will Act.
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Attitude of Health Personnel↗
Control of myofibrillar ATPase activity and force in myodystrophic muscle.
Myofibrillar ATPase activity was measured as a function of the free calcium concentration in skeletal muscles of control and myodystrophic mice. In addition, the force developed in skinned extensor digitorum longus (EDL) fibers of control and myodystrophic mice was measured as a function of the free calcium concentration, and a histomorphometric study was performed on soleus and EDL muscles of control and myodystrophic mice. The results showed that the myofibrillar ATPase activity and the force-generating mechanisms of control and myodystrophic muscles were controlled to the same relative degree by equivalent concentrations of calcium ions. Upon maximal activation of the ATPase activities, we measured 18% less activity in myodystrophic muscles than in control muscles. Maximal activation of the force-generating capacity in skinned fibers showed there was no significant difference in force produced in the control compared to myodystrophic fibers. The histomorphometric study revealed no alteration in the relative distribution of different fiber types in myodystrophic compared to control muscles. However, the histomorphometry did reveal a larger slow (type 1) relative cellular area compared to total cross-sectional area in myodystrophic muscle than in controls. We propose that the lower ATPase activity but equal force-generating capacity of myodystrophic muscles compared to control muscles is due to myodystrophic muscles being composed of a greater fraction of myofibrils from slow (type 1) fibers than control muscles.
Adenosine Triphosphatases↗
Echinococcus granulosus: failure of the eosin-exclusion test to demonstrate death of protoscoleces.
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Animals↗
Intraocular penetration of systemically administered antifungal agents.
Amphotericin B, 5-flucytosine (5-FC), and ketoconazole levels were estimated in vitreous and aqueous samples taken from four patients undergoing therapeutic vitrectomy for fungal endophthalmitis. The levels of amphotericin B in the vitreous of three patients were low (.04 - .17 microgram/ml). However, 5-FC was present in a concentration of 22.2 micrograms/ml in one patient. In another case the aqueous level of ketoconazole was 0.35 microgram/ml. The vitreous in the same patient contained 0.71 microgram/ml of the drug.
Amphotericin B↗
A stereological analysis of the tegumental mitochondria in Corrigia vitta (Trematoda: Dicrocoeliidae).
The tegumental mitochondria from the anterior, mid-ventral and mid-dorsal regions of the body surface of Corrigia vitta have been analysed using stereological and statistical methods. Mitochondria from the ventral tegument were more numerous and contained a greater density of cristae than either the anterior or dorsal tegumental mitochondria. A close association between the size and numbers of mitochondria in the anterior regions of tegument appears to be important in maintaining a relatively constant mitochondrial volume fraction. Results are discussed with respect to worm surface function in the intact host-parasite system.
Animals↗
Variability in isolate recovery rates from multiple and single breeds of outbred pigmented rabbits in an experimental model of Candida keratitis.
We evaluated variability of isolate recovery rates in an experimental model of Candida keratitis for both heterogeneous, pigmented, outbred rabbits and homogeneous Dutch-belted rabbits. Our purpose was to achieve more precise evaluation of topical antifungal agents in our model by substantially reducing the component of variance due to inter-rabbit differences. For the homogeneous Dutch-belted rabbits, the overall variance was reduced by a factor of 2.34 (p = 0.18) vis a vis the heterogenous outbred rabbits. The greatest reduction, a factor of 3.5, was achieved for the inter-rabbit component of variance. The upper bound for the hereditability measure was reduced from 29% to 18%. These data suggest that (1) researchers using animal models should perform a components of variance analysis to identify the factors influencing experimental precision, and (2) for our model, additional reduction in variability must come from refinement of experimental technique.
Analysis of Variance↗
Influence of the corneal epithelium on the efficacy of topical antifungal agents.
A model of deep stromal Candida albicans infection was established by injecting 25 microliters of a suspension containing 5 X 10(9) colony forming units/ml of the yeast into corneas of pigmented rabbits. In this model, the infection lasts for more than 8 days. Using quantitative techniques, the authors compared the efficacy of six topical antifungal agents in the presence of an intact epithelium and in corneas debrided of epithelium. In corneas debrided on a daily basis, the polyenes (amphotericin B 0.15% and 0.075% and natamycin 5%) exhibited a significant antifungal effect. When the epithelium was left intact, 5% natamycin and 0.075% amphotericin B were without effect, while the efficacy of the 0.15% preparation of amphotericin B was much reduced. Removal of the epithelium appeared to affect adversely the efficacy of flucytosine. The imidazoles were not efficacious in this model.
Administration, Topical↗
Efficacy of antifungal agents in the cornea. IV. Amphotericin B methyl ester.
Quantitative mycologic techniques were used to evaluate the efficacy of topical amphotericin B methyl ester in two models of yeast infection in rabbit eyes. Doses of 1%, 0.5%, and 0.15% were used in a model of superficial Candida albicans infection. The 1% dose of drug was highly efficacious, abolishing the disease after 2 days of treatment. With doses of 0.5% and 0.15%, decreasing efficacy was observed. Antifungal activity did not deteriorate when 1% prednisolone acetate was administered concomitantly with the 1% dose. In a model of deep stromal infection, the administration of topical 1% amphotericin B methyl ester was highly efficacious when the corneal epithelium was absent. Even in corneas with intact epithelium, a reduced though still significant effect was noted.
Administration, Topical↗
Structure-function relationships in lactose synthase. Structural requirements of the uridine 5'-diphosphate galactose binding site.
The structural requirements for the donor pyranosyl moiety of UDP-Gal in either galactosyl transfer or "lactose" biosynthesis have been determined. The 4"-deoxy analogue, UDP-4"-deoxyglucose, was synthesized and fully characterized as a donor substrate for galactosyltransferase. The relative rate of deoxyglucosyl transfer to glucose or GlcNAc acceptors was 5.5 +/- 0.6% of that of UDP-Gal as the substrate, with Km values in the same range as that for UDP-Gal or UDP-Glc. Several conclusions may be drawn as to the detailed structural requirements of the UDP-Gal binding site: an axial 4"-hydroxyl group on the pyranosyl moiety is necessary for precise substrate alignment as is also an equatorial 6"-CH2OH moiety. Where one or the other moiety was lacking (UDP-dGlc or UDP-Arab), the maximal rate of glycosyl transfer was ca. 1/20th that of UDP-Gal.
Binding Sites↗