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Biomedical subjects

D S Hull

Publications and source records attributed to D S Hull.

At least 73 records · Page 4Linked to original sources

Effect of iontophoretic and topical application of antiviral agents in treatment of experimental HSV-1 keratitis in rabbits.

Cathodal (-) iontophoresis of 9-beta-D-arabinofuranosyl-adenine 5'-monophosphate (vidarabine monophosphate; Ara-AMP) was performed once daily for 3 days for the treatment of experimental herpes simplex virus type 1 (HSV-1) keratitis in rabbit eyes, and the therapeutic efficacy was compared with that of topical treatment of Ara-AMP and idoxuridine (IDU) administered five times daily for 4 days. With the treatment initiated 24 hr after viral inoculation, Ara-AMP cathodal iontophoresis resulted in significant suppression of epithelial and anterior segment disease processes. Topical IDU (0.5%) or Ara-AMP (10%) also significantly improved the disease process when compared to the placebo-treated group; however, iontophoresis of Ara-AMP resulted in a more marked improvement. Slit-lamp examination indicated that iontophoresis did not cause any observable pathologic changes in corneal epithelium, stroma, conjunctiva, or iris of rabbit eyes. This experiment suggests that iontophoresis of Ara-AMP is a safe and effective approach for preventing the development of herpes simplex keratitis in rabbits.

Administration, Topical↗

Effect of intraocular miotics on corneal endothelium.

We investigated the use of commercially available intraocular preparations of acetylcholine chloride and carbachol for their effects on the physiological function and anatomical appearance of the corneal endothelium. Cornea endothelial cells that were perfused for 15 minutes in the specular microscope with 1% acetylcholine demonstrated no alteration in physiology or ultrastructure. Cornea endothelial cells perfused for 15 minutes with 0.01% carbachol demonstrated alterations in physiology during the first hour; however, physiological function returned to normal during the remaining two hours of perfusion in modified Krebs-Ringer bicarbonate solution. Electron microscopy demonstrated no cellular alterations.

Acetylcholine↗

Elective subjects for medical students preparing for a career in ophthalmology.

Questionnaires asking for information as to what medical school electives should be taken by a student contemplating a career in ophthalmology were sent to 280 practicing ophthalmologists. Seventy-two replies were received and indicated that a medical school background in neurosciences, ophthalmology, anesthesiology, otolaryngology, dermatology, and infectious disease are believed to be most important.

Education, Medical, Undergraduate↗

Cornea endothelial bicarbonate fluxes following preservation in solutions of varying composition.

Numerous modifications have been made in MK solution, primarily concerned with alterations in both bicarbonate concentration and PCO2. Variations of the solutions from high bicarbonate to low bicarbonate and either high or low PCO2 were made which resulted in a decreased net bicarbonate flux across the endothelium after a 3-day storage period. Even with drastic changes in the storage solution there was a relatively small change in the net bicarbonate flux. Higher passive fluxes were found at a pH above 8, and a higher net flux with a bicarbonate concentration of 17.5 nM or higher. Variation in PCO2 made little difference to the net endothelial fluxes; when a high PCO2 was used, there was a concurrent elevation of PO2 in the storage solution, but no beneficial effect was found on the endothelial transport system. It was apparent that a good storage solution contained a buffer (bicarbonate was better than phosphate) and 5% dextran and was at a neutral pH (between 7 and 8).

Animals↗

Iontophoresis of vidarabine monophosphate into rabbit eyes.

In order to investigate the efficacy of iontophoresis for increasing the penetration of vidarabine monophosphate into the eye, tritium-labeled vidarabine monophosphate was applied to rabbit eyes by topical and iontophoretic application, and the penetration of the compound into the eye, and its subsequent metabolism, were studied. At 20 min after treatment, the ratios of radioactivity for cathodal iontophoresis compared to topical application alone were cornea 8.6, aqueous humor 4.8, and iris 2.4; for 60 min the ratios were cornea 12.2 aqueous humor 17.5 and iris 2.5. In addition, the acid-soluble components were extracted from the cornea and aqueous humor. Vidarabine monophosphate, vidarabine, hypoxanthine arabinoside, adenosine, hypoxanthine, and adenine from the acid-soluble fraction were separated by thin-layer chromatography. The amount of vidarabine monophosphate and vidarabine in the cornea and aqueous humor from the iontophoretically treated group was six to 15 times higher than from the group that received topical application of the drug. It was concluded that cathodal iontophoresis resulted in significantly increased penetration of the antiviral drug vidarabine monophosphate into the anterior chamber of the eye. The effects of iontophoresis of vidarabine monophosphate on corneal epithelium, as observed by scanning electron micrographs, were equal to or less than those seen with the topical application of widely used preservatives in ophthalmic preparations.

Adenine↗

Effect of xenon arc photocoagulation on corneal endothelium.

Xenon arc photocoagulation of the fundus of pigmented rabbits resulted in no corneal endothelial cell damage when the experiment was designed to minimize corneal temperature rise by frequent topical instillations of ophthalmic irrigating solution.

Animals↗

Rabbit endothelial response to ophthalmic preservatives.

The endothelial surface of isolated rabbit corneas were perfused for three hours with varying concentrations of benzalkonium chloride and cetylpyridinium chloride. The threshold for physiological and ultrastructural alteration of corneal endothelium is approximately 0.0001% for benzalkonium chloride and 0.01 mM for cetylpyridinium chloride. The effects of the surfactants can be induced with as little as a 15-minute exposure without subsequent recovery. Use of ophthalmic medications or irrigating solutions containing these agents inside the eye is potentially hazardous to the corneal endothelium. Topical administration of 0.133% benzalkonium chloride to the anterior surface of deepithelialized in vivo corneas (five doses, seven minutes apart) caused no alterations of corneal endothelial cell function or ultrastructure.

Animals↗

Modification of the antibiotic system in M-K medium.

Corneal endothelial cell function and ultrastructure were studied in rabbit corneas stored in M-K medium with different antibiotics. At concentrations about ten times greater than their minimum inhibitory concentrations, tobramycin, gentamicin, polymixin B, penicillin and streptomycin mixture, cephaloridine, and cephalothin did not damage corneal endothelia. Corneas stored in M-K medium with bacitracin did not have temperature reversals as did other corneas after storage. This is probably not significant since they maintained almost constant thickness and the endothelial layer remained intact.

Animals↗

Effect of vidarabine and related compounds on corneal endothelium.

The endothelial surface of rabbit corneas was perfused with vidarabine monophosphate (with and without adenosine deaminase inhibitor), vidarabine (with and without adenosine deaminase inhibitor), and ara-Hx. In concentrations 10 times to 1,500 times higher than those that have been obtained in the aqueous humor following topical, subconjunctival, or systemic administration, none of the compounds had any effect on corneal endothelial cell function or ultrastructure for the duration of the experimental model.

Animals↗

Corneal endothelium bicarbonate transport and the effect of carbonic anhydrase inhibitors on endothelial permeability and fluxes and corneal thickness.

Unidirectional fluxes of bicarbonate across the corneal endothelium were determined. A net flux of bicarbonate from the stromal to aqueous-facing surface was demonstrated. Under conditions of carbonic anhydrase inhibition the net bicarbonate flux was reduced by 54 percent and the passive water permeability of the endothelium was increased. Experiments with the specular microscope demonstrated an increased rate of corneal swelling under conditions of carbonic anhydrase inhibition. Attempts to identify H+ as the cation moving with the bicarbonate ion to maintain electroneutrality were not successful because of the impossibility of sustaining a differential H+ concentration difference across the endothelium.

Animals↗

Dextran uptake into, and loss from, corneas stored in intermediate-term preservative.

This investigation demonstrates that dextran passes into rabbit corneas stored in M-K medium prior to corneal transplantation. An equilibrium between dextran in the cornea and in the M-K medium is reached at about 24 hours. Post-keratoplasty dextran efflux is rapid with about 70 to 75 per cent being lost within one to three hours and 99 per cent being lost in 12 hours.

Animals↗

Effect of brinolase on corneal endothelium.

We investigated Brinolase, a substance producing enzymatic zonulysis, for effects on the physiological and anatomical function of the corneal endothelium in the specular microscope. Concentrations of 100 C2 units/ml perfused for ten minutes did not appear to damage the corneal endothelium. Longer perfusions or higher concentrations possibly produced alterations in the physiological functions of the endothelium, but no significant anatomic change was demonstrated. Longer perfusion times with high concentrations (1,600 C2 units/ml) resulted in the formation of holes which perforated the corneal stroma.

Animals↗

Corneal water and electrolyte content following storage in moist chamber and MK medium.

Rabbit corneas were subjected to MK-medium or moist-chamber storage for periods up to 7 days. Sodium, potassium, and chloride concentrations and hydration were measured. The hydration of corneas stored in MK medium was less than that of those stored in moist chambers. The sodium concentration of MK corneas remained stable for up to 7 days; the potassium concentration, however, decreased with increasingly longer periods of storage. Chloride concentrations quickly equilibrated with the high chloride level of MK medium. The concentration of sodium and chloride in moist chamber-stored corneas fell with progressively longer storage periods. Potassium showed an initial decrease in concentration followed by an increase in concentration that paralleled, and equilibrated with, the increasing acqueous humor concentration.

Animals↗

Effect of epinephrine on the corneal edothelium.

Intracameral epinephrine has been advocated for treatment of iris bleeding and inadequate pupillary dilatation during intraocular surgery. Commercial epinephrine 1:1000 with its preservative sodium bisulfite damaged corneal endothelial function and ultrastructure in rabbit and monkey eyes with sodium bisulfite the source of the damage. Endothelial damage can be prevented with a 1:5000 dilution of commercially available epinephrine in 0.1% sodium bisulfite or freshly prepared epinephrine bitartrate 1:1000 with a bicarbonate Ringers.

Animals↗

Adenine arabinoside in idoxuridine unresponsive and intolerant herpetic keratitis.

Twenty-two patients with active herpes simplex dendritic keratitis, in whom topical idoxuridine was unsuccessful in controlling their disease, were treated with topical adenine arabinoside (ara-A), a purine analogue effective against many DNA viruses. This drug was an effective antiviral agent in these patients. No signs of ocular or adnexal toxicity were noted.

Adenine↗

Clinical experience with the therapeutic hydrophilic contact lens.

Hydrophilic contact lenses were prescribed for 62 patients with a variety of corneal diseases. The lens was must successful for relief of pain in bullous keratropathy and in the healing of recurrent erosions. Its value in improving vision in bullous keratopathy depends on the stage of corneal edema and is not impressive in long-standing edema with scarring. The lens may be of value in patients with sterile indolent ulcers and in alkali-burned corneas with large epithelial defects after conventional therapy has failed. Caution is advised in fitting patients with the dry eye syndromes. Patients with minimal corneal scars due to keratoconus may benefit from a soft lens. Complications related to the use of hydrophilic lenses in this group of 62 patients are also discussed.

Alkalies↗