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Biomedical subjects

R Fiscella

Publications and source records attributed to R Fiscella.

At least 37 records · Page 2Linked to original sources

Retinal toxicity of ganciclovir in vitrectomy infusion solution.

The authors investigated the retinal toxicity of the antiviral agent ganciclovir after its addition to vitrectomy infusion fluid in rabbit eyes. Intravitreal infusion of the drug in concentrations up to 30 micrograms/ml produced no electroretinographic or histologic changes suggestive of retinal toxicity. Ganciclovir in vitrectomy infusion fluid has potential therapeutic benefit in viral retinitis (particularly in cytomegalovirus retinitis) associated with vitreous traction or rhegmatogenous retinal detachment. Based on the median inhibitory doses of ganciclovir against various herpes group viruses and the results of this study, a concentration of 30 micrograms/ml or less of the drug is recommended for vitrectomy infusion solution.

Acyclovir↗

Intravitreal injection of liposome-encapsulated ganciclovir in a rabbit model.

The authors determined the intravitreal clearance of liposome-encapsulated ganciclovir. Liposome-encapsulated ganciclovir (84.1 micrograms/0.1 ml) was injected into the vitreous cavity of New Zealand rabbits, which were killed at 24 hours and 7, 14, and 28 days after injection. Total ganciclovir concentrations in the vitreous, up to 28 days, were higher than ID50 (50% inhibitory dose) for different clinical and laboratory strains of viruses belonging to the herpes simplex family.

Acyclovir↗

Age and education effects in the diagnosis of attention deficit disorder, residual type in an alcoholic population.

Two self-report measures that have been used to screen an alcoholic population for Attention Deficit Disorder, Residual Type (ADD-RT) are the Childhood Symptom Checklist and a listing of the DSM-III criteria. Both measures have evidence supporting their validity as screening instruments for ADD-RT in alcoholics. This study further explores the properties of these instruments by determining whether the age or educational level of alcoholic patients relates to their performance on these measures. No differences were found between the scores of younger and older patients. However, alcoholic patients with more education had fewer DSM-III symptoms of ADD-RT, but did not have fewer symptoms on the Childhood Symptom Checklist. The difference in performance on these two previously consistent measures is noted. Future research might explore the possibility that the DSM-III symptoms of ADD-RT are more sensitive to functional deficits in adults than the Childhood Symptoms Checklist, which asks for symptoms of Attention Deficit Disorder as a child.

Adult↗

Toxicity of intravitreal injection of fluconazole in the rabbit.

Fluconazole is a new bis-triazole derivative proven highly effective against Candida in various animal models. To determine its potential use in exogenous fungal endophthalmitis, 13 New Zealand white rabbits were given intravitreal injections of up to 100 micrograms/0.1 mL of the antifungal. All eyes underwent biomicroscopy, ophthalmoscopy and electroretinography before and after the procedure. No evidence of toxic intraocular effects was detected with these techniques or on light microscopy, performed 8 days after injection. The results suggest that fluconazole has potential application in the treatment of exogenous fungal endophthalmitis.

Animals↗

Retinal toxicity of combination antiviral drugs in an animal model.

We investigated the retinal toxicity of various combinations of four antiviral agents in intravitreal injection and vitrectomy infusion solutions in the rabbit. The nontoxic concentration of each individual agent for intravitreal injection and for vitrectomy infusion has previously been described. Our results support the concept that concentrations of 200 micrograms/0.1 mL of trifluridine, 400 micrograms/0.1 mL of hydroxyacyclovir, 200 micrograms/0.1 mL of acyclovir and 30 micrograms/0.1 mL of vidarabine can be combined for intravitreal injection without toxic retinal effects. Moreover, 60 micrograms/mL of trifluridine, 20 micrograms/mL of hydroxyacyclovir, 40 micrograms/mL of acyclovir and 8 micrograms/mL of vidarabine can be combined in vitrectomy infusion solutions without retinal damage. Further study is needed to determine the full potential of such combinations.

Acyclovir↗

Duration of therapeutic levels of intravitreally injected liposome-encapsulated clindamycin in the rabbit.

We investigated an intravitreal preparation of liposome-encapsulated clindamycin phosphate to determine the duration of therapeutic levels of the drug in the vitreous cavity. Twenty New Zealand albino rabbits were given an intravitreal injection of 750 micrograms/0.1 mL of encapsulated clindamycin (10 animals) or 800 micrograms/0.1 mL of nonencapsulated clindamycin (10 animals) and then were killed immediately or 6, 12, 24 or 48 hours later. The mean concentration of encapsulated clindamycin in the vitreous at 48 hours was 28.4 micrograms/mL, while that of nonencapsulated clindamycin at 24 hours was 2.3 micrograms/mL. The estimated elimination rate of nonencapsulated clindamycin was 3 hours, compared with approximately 10 hours for the encapsulated preparation. This drug delivery system warrants further investigation for possible use in humans.

Animals↗

Toxicity of intravitreally administered alpha-interferon.

We studied the toxicity of single doses of intravitreally administered alpha-interferon in albino rabbits. Doses of 420,000, 210,000, 105,000, 52,500, and 26,250 units/0.1 cc showed no significant histologic changes by light microscopy or altered retinal function assessed by photopic and scotopic electroretinography.

Animals↗

A comparison of two dose regimens of epsilon aminocaproic acid in the prevention and management of secondary traumatic hyphemas.

Fifty-nine patients who sustained hyphema following blunt trauma were randomly assigned prospectively to either of two dose regimens of epsilon aminocaproic acid (Amicar). Twenty-six took an oral dosage of 50 mg/kg ("half dose") every four hours for five days, up to a maximum of 30 g/day, and 33 patients received 100 mg/kg ("full-dose") every four hours up to a maximum of 30 g/day. Five patients in the full-dose group experienced dizziness, hypotension, and syncope. Half-dose Amicar substantially reduced such serious side effects (P = 0.063), had no adverse effect on the reduced rate of recurrent hemorrhages (P = 0.22), and was more cost effective than the full-dose regimen. When the two patients in the half-dose group receiving 30 g/day of Amicar were deleted, however, the comparison of dizziness and hypotension in the two groups became more significant (P = 0.050). The incidence of nausea and vomiting was approximately the same in both groups (P = 0.52). Serum Amicar levels were within the range of plasminogen inhibition at both dose levels. Prior aspirin ingestion appeared to have no influence on the rate of rebleeding (P = 0.58).

Administration, Topical↗

Intravitreal trifluorothymidine and retinal toxicity.

Intraocular trifluorothymidine was administered to one group of albino rabbits as an intravitreal injection, and to a second group of albino rabbits in the infusion solution during pars plana vitrectomy. The eyes of both populations were evaluated with preoperative and postoperative indirect ophthalmoscopy, electroretinography, and histologic examination. From these data, it was determined that an intravitreal injection of 200 micrograms/0.1 ml and a vitrectomy solution containing a concentration of 60 micrograms/ml trifluorothymidine were nontoxic to the rabbit eye.

Animals↗

Intraocular penetration of new antiviral agent, hydroxyacyclovir (BW-B759U).

9-[(2-hydroxyl-1-(hydroxymethyl)ethoxy]methyl)guanine (hydroxyacyclovir) is a nucleoside analogue with a high degree of efficacy against herpes simplex virus types 1 and 2 and cytomegalovirus (CMV). This antiviral agent demonstrates a low toxicity towards uninfected cells. Intraocular levels in rabbits were evaluated following subconjunctival, intravenous, intravitreal and topical administration. Retinal toxicity studies were performed. Hydroxyacyclovir may have applications in the treatment of deep herpetic infections, CMV retinitis, and acute retinal necrosis.

Acyclovir↗

Intraocular 9-([2-hydroxy-1-(hydroxymethyl) ethoxy] methyl) guanine levels after intravitreal and subconjunctival administration.

Clearance studies in rabbits following intravitreal injection of 400 micrograms of 9-([2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl) guanine demonstrated levels of the antiviral at 60 hours above the in vitro ID50 for several strains of human cytomegalovirus. Intravitreal administration of this new antiviral may have therapeutic application in the treatment of acute retinal necrosis and cytomegalovirus retinitis complicating acquired immune deficiency syndrome (AIDS).

Acyclovir↗

Toxicity of intravitreal interferon.

We evaluated the toxicity of injecting human fibroblast interferon intravitreally in rabbit eyes. A single intravitreal injection of 166,660 units/0.1 ml was nontoxic to ocular structures, as demonstrated by electroretinographic and histologic examination.

Animals↗

Effects of selected repeated intravitreal chemotherapeutic agents.

The toxic effects of repeated intravitreal injections of selected chemotherapeutic agents were studied in female albino rabbits. Three groups of eyes participated in each therapeutic regimen. Agents studied were doxorubicin (dox), 3 and 5 micrograms; 5-fluorouracil (5-FU), 0.375 and 1.0 mg; bleomycin (bleo), 15 micrograms; thiotepa (thio), 12 micrograms; etoposide (VP-16), 150 micrograms; and methotrexate (MTX), 600 mic. Toxicity was evaluated using electroretinography (ERG) in 66% and histopathology in 100% of eyes 5 weeks following the initial injection and at least 2 weeks after the final injection of each series. Eyes receiving 2 doses of dox 3 micrograms showed no toxicity. Eyes receiving 3 or more doses of dox 3 micrograms and those treated with 2 or more doses of dox 5 demonstrated toxicity proportional to the number of doses received. Eyes treated with 5-FU 0.375 or 1.0 mg showed no toxic reaction. Successive intravitreal injections of 5-FU, 0.375 mg and dox 5 micrograms, and 5-FU, dox, and bleo produced no toxicity. Eyes treated with successive intravitreal injections of 5-FU, dox, bleo, and thio displayed decreased ERG response. The addition of VP-16 and MTX resulted in further loss of ERG response and more severe histologic retinal changes.

Animals↗

In vitro evaluation of cellular inhibitory potential of various antineoplastic drugs and dexamethasone.

We evaluated the in vitro cellular inhibitory rates of eight antineoplastic agents and dexamethasone for rabbit retinal pigment epithelial cells and rabbit corneal fibroblasts. Doxorubicin was the most effective chemotherapeutic agent to inhibit cellular proliferation (-90%). Compared to the controls, the percentage variation in cell number for single agents ranged from +26% to -90%. Chemotherapy drugs in combination also were evaluated and found to be not superior to the single agents. Cellular inhibitory rates for combination agents ranged from -34% to -72%. Dexamethasone in the concentrations used did not significantly inhibit or stimulate cellular proliferation.

Animals↗

Clearance of intravitreal 3H-fluorouracil.

The clearance of intravitreally administered 5-fluorouracil (5-FU) was studied under five experimental conditions. The same nontoxic dose resulted in similar initial intravitreal concentrations and cleared rapidly from all eyes (approximately 90% clearance within eight hours). Half-life values ranged from 46 to 168 minutes. The longest half-life occurred in aphakic-vitrectomized eyes in which hyaluronic acid (Healon) was substituted for vitreous (168 minutes). A similar half-life was found in normal eyes (150 minutes). The shortest half-life occurred in aphakic-vitrectomized eyes postoperatively (46 minutes). Intermediate half-life values occurred in vitrectomized but phakic eyes postoperatively (67 minutes) and in aphakic-vitrectomized "quiet" eyes (at least two weeks postoperatively) (82 minutes).

Animals↗