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Biomedical subjects

L Chisholm

Publications and source records attributed to L Chisholm.

At least 19 recordsLinked to original sources

Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP.

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant beta-amyloid precursor protein (APP), thus modulating the APP-Abeta (beta-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed Abeta deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or Abeta influences the formation of neurofibrillary tangles. The interaction between Abeta and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.

Alzheimer Disease↗

Target cell susceptibility to lysis by human natural killer cells is augmented by alpha(1,3)-galactosyltransferase and reduced by alpha(1, 2)-fucosyltransferase.

Susceptibility of porcine endothelial cells to human natural killer (NK) cell lysis was found to reflect surface expression of ligands containing Gal alpha(1,3)Gal beta(1,4)GlcNAc [corrected], the principal antigen on porcine endothelium recognized by xenoreactive human antibodies. Genetically modifying expression of this epitope on porcine endothelium by transfection with the alpha(1,2)-fucosyltransferase gene reduced susceptibility to human NK lysis. These results indicate that surface carbohydrate remodeling profoundly affects target cell susceptibility to NK lysis, and suggest that successful transgenic strategies to limit xenograft rejection by NK cells and xenoreactive antibodies will need to incorporate carbohydrate remodeling.

Animals↗

Repair of Descemet's membrane detachment with perfluoropropane (C3F8)

PURPOSE: To report the use of perfluoropropane (C3F8) gas in the repair of Descemet's membrane detachments. METHODS: Descemet's membrane detachments after cataract surgery in three eyes and pars plana vitrectomy in a fourth underwent anterior-chamber gas-exchange descemetopexy with an isoexpansile 14% mixture of C3F8 to facilitate reattachment of Descemet's membrane. RESULTS: Descemet's membrane detachment was successfully reattached after anterior-chamber gas exchange with 14% C3F8 in three of the four eyes treated. The fourth eye treated with 14% C3F8 probably failed Descemet's membrane reattachment because of an unrecognized viscoelastic bleb situated anterior to Descemet's membrane. No corneal decompensation or fluctuations in intraocular pressure were believed to be attributable to isoexpansile C3F8 gas exchange. CONCLUSION: Early recognition and repair of Descemet's membrane detachments may prevent complications, such as corneal decompensation, corneal opacities and edema, and an overall decline in visual acuity. Isoexpansile C3F8 is demonstrated as a safe and efficacious alternative for the repair of Descemet's membrane detachment.

Aged↗

Reproducibility of topographic measurements of the macula with a scanning laser ophthalmoscope.

BACKGROUND: The Heidelberg retina tomograph, a scanning laser ophthalmoscope that uses confocal optics to provide high resolution of images, is able to scan the retina in three dimensions to obtain quantitative topographic measurements. The authors evaluated its usefulness for measuring macular lesions by determining the reproducibility of its topographic measurements at the macula. METHODS: For each of ten healthy patients, the authors took five images with the patient's right eye undilated and five with the eye cyclopleged and dilated. As a measure of reproducibility, the standard deviation of height measurements for the same location at the macula was calculated for each patient and then the pooled standard deviation for all patients was calculated. The authors performed similar calculations for the mean depth within a contour line. RESULTS: The pooled standard deviation for height measurements was 47.4 microns in undilated eyes and 36.0 microns in cyclopleged, dilated eyes. The authors obtained an extremely low standard deviation of 2.2 microns when the software calculated relative differences between measurements, such as the mean depth within a contour line. When the average of three height measurement values on 1 day was compared with the average of the three values on another day, the 95% confidence interval was +/- 58.7 microns for mean height values and +/- 3.7 microns for mean depth values within a contour line. CONCLUSIONS: The authors obtained good reproducibility for height measurements with the Heidelberg retina tomograph and excellent reproducibility when the instrument calculated relative differences in height measurements. The authors recommend that patients, especially young patients, be dilated and cyclopleged to obtain lower variability of measurements. The scanning laser ophthalmoscope could potentially be used to quantify small changes in retinal lesions.

Adult↗

A cancer day hospital: an alternative approach to caring for patients in clinical trials.

The National Institutes of Health recently established a large cancer day hospital (CDH) to address the need to support new research initiatives in the face of a shrinking research budget. By design, the CDH is very much a nursing unit. It employs a collaborative practice model of patient care delivery that emphasizes the nurses' independent clinical- and protocol-related responsibilities and roles. The CDH is designed to be budget neutral. An increased outpatient throughput and a decrease in inpatient days for at least one large protocol population (patients receiving therapy for prostate cancer) have been demonstrated. With a steadily increasing number of patients, the CDH appears to be a well-accepted and cost-effective site for the care of patients enrolled in oncology clinical trials.

Aftercare↗

Toxicity and pharmacokinetics of intravitreally injected ciprofloxacin in rabbit eyes.

To assess the toxicity of intraocular injection of ciprofloxacin, 22 New Zealand white rabbits received midvitreal injections of 100, 200, 400, 800 or 3200 micrograms of ciprofloxacin in 0.1 mL of distilled water (39 eyes) or 0.1 mL of distilled water only (5 eyes). The ocular pharmacokinetics of intravitreally injected ciprofloxacin was determined by aqueous humour and vitreous sampling 1, 2, 4, 8, 12, 18 or 24 hours after midvitreal injection of 100 micrograms of the drug in one eye each of 25 New Zealand white rabbits. The samples were analysed by means of a disc diffusion bioassay. No ocular damage was noted on ophthalmoscopy at any of the concentrations tested. Histologic study showed mild, transient vacuolation of the nerve-fibre layer in all eyes, including the control eyes, 2 hours after injection; at 24 hours no vacuolation was evident except at concentrations of 800 and 3200 micrograms, at which plexiform layer damage was evident. Peak aqueous and vitreous levels of ciprofloxacin were obtained at 1 hour (0.59 and 27.26 micrograms/mL respectively); the vitreous level fell to below 1.0 micrograms/mL 12 hours after injection. We conclude that intravitreally injected ciprofloxacin may be a safe and useful antibiotic in the treatment of aminoglycoside-resistant bacterial endophthalmitis.

Animals↗

Effect of vitrectomy on the ocular distribution of gentamicin in the rabbit.

To determine whether vitrectomy affects the ocular distribution of intravitreally injected gentamicin sulfate, 25 pigmented rabbits received an intravitreal injection of gentamicin (control group), and 25 other pigmented rabbits underwent pars plana vitrectomy followed by an intravitreal injection of gentamicin (experimental group). The animals were killed in groups of five 1, 3, 6, 12 and 24 hours after the injection. The mean retinal gentamicin levels 1 and 3 hours after the injection were significantly higher in the experimental group than in the control group (p less than 0.01). The mean gentamicin level in the aqueous humour was significantly lower in the experimental group than in the control group 1 hour (p less than 0.01), 6 hours (p less than 0.01) and 24 hours (p less than 0.001) after the injection. The mean corneal gentamicin level 24 hours after the injection was significantly lower in the experimental group than in the control group (p less than 0.05). There was no significant difference in mean choroidal gentamicin level between the two groups. We conclude that vitrectomy significantly affects the ocular distribution of gentamicin in the rabbit.

Animals↗