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Biomedical subjects

R Fiscella

Publications and source records attributed to R Fiscella.

At least 19 recordsLinked to original sources

The effect of minoxidil on keratocyte proliferation in cell culture.

PURPOSE: To determine if minoxidil inhibits keratocyte proliferation in a nontoxic manner. METHODS: Rabbit keratocytes were cultured in Eagle's minimum essential medium supplemented with fetal bovine serum. Minoxidil varying in concentration from 10(0) to 10(3) micrograms/ml was added to the culture medium and incubated for 7 days. The cultures were inspected for morphologic appearance and the cell number was determined at 1, 3 and 7 days after the addition of minoxidil. After 7 days of incubation, minoxidil was withdrawn from the cell culture medium and the cells were examined 3 and 7 days thereafter. In addition, a nonradioactive cytotoxic assay was performed to determine if toxicity is associated with the presence of minoxidil. RESULTS: Minoxidil inhibited keratocyte proliferation in a dose-dependent fashion. 29% of control growth was achieved when keratocytes were cultured for 7 days in 10(3) micrograms/ml, whereas 82% control growth was achieved when keratocytes were cultured in 10(2) micrograms/ml of minoxidil. Intermediate concentrations between 10(2) and 10(3) micrograms/ml produced a linear decline in cell counts in a dose-dependent fashion. The concentration of minoxidil required for 50% control growth at 7 days extrapolated from the dose-response curve was 600 micrograms/ml. Upon withdrawal of minoxidil, cell counts returned to baseline for concentrations of 10(2) micrograms/ml or less. Phase contrast microscopy revealed that the presence of minoxidil was associated with intercellular separation, enlargement of cell bodies and elongated processes. After the withdrawal of minoxidil, the cells in all media reassumed the morphological features of normal keratocytes which included a regular fusiform shape and extensive intercellular contact. The nonradioactive cytotoxic assay revealed the lack of cytotoxicity at all concentrations of minoxidil based on a lack of lactate dehydrogenase release. CONCLUSIONS: Minoxidil inhibits keratocyte proliferation by a nontoxic mechanism. It might be particularly useful for modulating corneal wound healing following excimer laser photorefractive keratectomy.

Animals↗

The effect of propranolol versus placebo on resident surgical performance.

PURPOSE: To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety. METHODS: In this randomized, double-masked, crossover study, 5 third-year ophthalmology residents ingested a capsule containing either propranolol, 40 mg, or placebo 1 hour prior to performing ophthalmic microsurgery. All residents were healthy men under age 30 years. Prior to commencement of the study, all participants had successfully been administered a test dose of propranolol without side effects. The study took place over a 10-week period. At the conclusion of each case, both the resident and attending surgeon observer independently completed a form grading, on a sliding scale: (1) amount of overall tremor; (2) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction; (3) anticipated difficulty of the case; (4) actual difficulty with the case; and (5) anxiety (surgeon only). In addition, the type of procedure performed, complications encountered, and surgeon side effects were recorded. The data were analyzed with a 2-way analysis of variance for unbalanced data. RESULTS: A total of 73 surgical cases were performed; the surgeons were administered propranolol for 40 cases and placebo for 33. As judged by the resident surgeon, there was a highly significant effect of propranolol in decreasing anxiety (P = .0058), reducing surgical tremor overall (P < .0001), and reducing tremor while placing the first 3 sutures following lens extraction (P < .0001). There was no treatment-by-surgeon interaction for any of the measures. Complications and difficulty of the case, as judged by both the resident and attending surgeons, were not significantly different in the propranolol versus placebo groups (P > .05). There were no side effects reported or observed in any of the surgeons. CONCLUSIONS: Propranolol, 40 mg, administered 1 hour prior to surgery, significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient. However, it is unknown whether decreased tremor and anxiety improved surgical outcome.

Adrenergic beta-Antagonists↗

Effectiveness of apraclonidine and acetazolamide in preventing postoperative intraocular pressure spikes after extracapsular cataract extraction.

We studied the effectiveness of two prophylactic agents in controlling early postoperative intraocular pressure (IOP) increases after cataract surgery. Fifty-four nonglaucomatous patients received either topical 1% apraclonidine, one drop before and after surgery, or sustained-release acetazolamide, 500 mg, or no medication at the completion of planned extracapsular cataract extraction (ECCE). Mean baseline IOPs were similar among patients randomized to the apraclonidine, acetazolamide, and control groups: 15.29 mm Hg, 15.33 mm Hg, and 14.26 mm Hg, respectively. At 3 hours postoperatively, IOPs were significantly lower in the apraclonidine group (11.13 mm Hg, P = .035), nonsignificantly lower in the acetazolamide group (13.3 mm Hg, P = .17), and significantly increased in the control group (21.32 mm Hg, P = .003). One eye in the apraclonidine group and six in the control group had IOPs greater than 30 mm Hg. At 24 hours, the only statistically significant difference was in the control group, whose mean IOPs remained elevated (21.83 mm Hg, P = .0008). One eye in the apraclonidine group, two in the acetazolamide group, and five in the control group had IOPs greater than 30 mm Hg. We found a significant early IOP reduction with apraclonidine given topically preoperatively and at the completion of planned ECCE.

Acetazolamide↗

Intraocular penetration of topical tissue plasminogen activator.

Fifty-eight eyes of 31 anesthetized rabbits received one drop of proparacaine hydrochloride, 0.05%, and two drops of tissue plasminogen activator (tPA) separated by 5 minutes. Four eyes of two additional rabbits had epithelial defects created before drug delivery. Tissue plasminogen activator in multiple doses was given to eight eyes of four other rabbits. We used this dosing regimen to investigate the effect of topical tPA on anterior chamber fibrin clots in three rabbits. A two-site enzyme-linked immunosorbent assay test was used to measure tPA levels in the aqueous samples, obtained by paracentesis in each eye. Of 53 eyes treated with the original dosing regimen, 21 (40%) had detectable tPA aqueous levels. Blood and aqueous from eyes of untreated control rabbits, contralateral control eyes of treated rabbits, and eyes with epithelial defects had nondetectable tPA. Multiple tPA drop dosing resulted in 75% of aqueous samples with detectable tPA and a higher average tPA concentration than the original dosing regimen. Eyes treated with tPA showed a significantly faster resolution of anterior chamber fibrin clots than did control eyes.

Administration, Topical↗

Ocular toxicity of experimental intravitreal itraconazole.

We investigated itraconazole, a new triazole antifungal agent that poorly penetrates ocular tissues after oral administration. We injected itraconazole in doses from 10 to 100 micrograms dissolved in 100% dimethyl sulfoxide into the eyes of New Zealand rabbits. Ocular toxicity studies performed five weeks after administration showed no substantial retinal or histopathologic changes in eyes injected with either 100% dimethyl sulfoxide or 10 micrograms of itraconazole. Higher doses caused focal areas of retinal necrosis. Our results indicated that intravitreal doses of 10 micrograms or less of itraconazole may be beneficial in the treatment of fungal endophthalmitis.

Animals↗

Aminocaproic acid versus prednisone for the treatment of traumatic hyphema. A randomized clinical trial.

One hundred twelve patients who sustained hyphema after blunt trauma were enrolled in a double-blind randomized clinical trial to determine the relative efficacies of aminocaproic acid (Amicar) and systemic prednisone for reducing the rate of secondary hemorrhage. Fifty-six patients received an oral dosage of 50 mg/kg of aminocaproic acid every 4 hours for 5 days, up to a maximum of 30 g daily, and 56 patients received an oral dosage of 40 mg of prednisone daily (adjusted for weight) in two divided doses. Placebo pills and liquids were given to each patient to mask the treatment schedules. There were no statistically significant differences between the patient populations for any demographic or clinical characteristic (e.g., visual acuity, intraocular pressure [IOP], initial hyphema size) measured in the study. Blacks comprised 53% of the study population, and the mean age of the patients was 23.5 years. Four patients in each of the treatment groups experienced a secondary hemorrhage; the rebleed rate was 7.1% in each group.

Administration, Oral↗

Intravitreal U75412E: a new free radical scavenger.

Free-radical-mediated tissue damage is thought to be involved in a multitude of ophthalmic pathologies. Therefore, drugs that scavenge free radicals may find wide clinical application. A new chemical class of antiinflammatory agents, the 21-aminosteroids, has been developed as free radical scavengers. These agents are thought to inhibit lipid peroxidation and prevent the release of free arachidonic acid from injured cell membranes. In the present study, we investigated the intraocular toxicity of one of the 21-aminosteroids, U75412E. Intravitreal doses of up to 0.1 mg of U75412E were nontoxic to rabbit ocular tissues.

Animals↗

Toxicity of intravitreal oxiconazole.

Oxiconazole, a new imidazole derivative, has a broad antifungal spectrum in vitro and in vivo. Adult New Zealand white rabbits were injected intravitreally with doses ranging from 10 to 100 micrograms of this drug. Eyes were evaluated with preoperative and postoperative biomicroscopy and indirect ophthalmoscopy, electroretinography, and light microscopy. From these data, it was determined that an intravitreal injection containing a concentration of up to 100 micrograms per 0.1 milliliter of oxiconazole was nontoxic to the rabbit eye.

Animals↗

Achromobacter xylosoxidans corneal ulcer in a therapeutic soft contact lens wearer.

Achromobacter xylosoxidans is an opportunistic organism that is usually seen in immunocompromised or immunosuppressed patients. It is an aerobic gram-negative rod, often confused with other more commonly seen gram-negative bacteria such as Pseudomonas aeruginosa. The organism is usually sensitive to extended spectrum penicillins such as carbenicillin and usually resistant to aminoglycosides and first generation cephalosporins. We wish to describe a corneal ulcer from A. xylosoxidans that developed in a patient wearing a therapeutic soft contact lens. The patient did not have a preexisting microbial keratitis and was not receiving corticosteroid therapy.

Aged↗

Ocular toxicity after intravitreal injection of terconazole.

Terconazole, a new triazole antifungal agent, was injected intravitreally in doses ranging from 10 to 100 micrograms dissolved in dimethyl sulfoxide (DMSO) 60% into the eyes of New Zealand rabbits. Three control eyes received only DMSO. The eyes were evaluated with biomicroscopy, indirect ophthalmoscopy, electroretinography, and histopathologic examination. From these data, it was determined that an intravitreal injection containing a concentration of 10 micrograms/0.1 mL of terconazole is not toxic to the rabbit eye.

Animals↗

The intraocular penetration and retinal toxicity of teicoplanin.

We investigated the intraocular penetration and retinal toxicity of teicoplanin, a relatively new glycopeptide antibiotic with activity similar to vancomycin when used to inhibit staphylococci and other gram positive organisms, particularly Streptococcus faecalia. Topically administered teicoplanin penetrated poorly into the aqueous and vitreous in rabbit eyes. Subconjunctival injection of the drug yielded aqueous levels above the minimum inhibiting concentration (3.1 micrograms/ml) only at one hour after injection. In the vitreous, drug levels were above the mean inhibitory concentration at 30 minutes after the subconjunctival injection, but rapidly declined thereafter. The maximum nontoxic, single-dose, intravitreal injection was 750 micrograms/0.1 ml. Rabbits received 8 micrograms/ml of teicoplanin in an intravitreal infusion solution without demonstrable retinal toxicity.

Animals↗

Retinal toxicity of intravitreal ethyldeoxyuridine and zinc.

We investigated the toxicity of intravitreal zinc sulfate, zinc gluconate, and ethyldeoxyuridine (EDU) in albino rabbits. Various concentrations of EDU were added to the infusion solution during pars plana vitrectomy. Retinal changes were observed by light microscopy after intravitreal injections containing 20 micrograms of zinc gluconate, all concentrations of zinc sulfate, and 400 micrograms of EDU. No histologic or electroretinographic alterations occurred with doses of 15 micrograms or less of zinc gluconate or 200 micrograms or less of EDU. When added to the vitrectomy solution, concentrations of 20 micrograms/mL or less of EDU appeared nontoxic to the rabbit retina.

Animals↗

Intravitreal toxicity of cotrimoxazole.

We investigated the intravitreal toxicity of cotrimoxazole (trimethoprim 80 mg and sulfamethoxazole 400 mg/5 ml of injection fluid) in albino rabbits. Eyes injected intravitreally with 1600 micrograms/0.1 cc (reported in trimethoprim concentration) exhibited no histologic or abnormal electroretinographic responses after 14 days. A vitrectomy infusion solution containing 32 micrograms/ml (reported in trimethoprim concentration) produced no toxicity, as demonstrated either by electroretinography or histology. Cotrimoxazole appears to be well-tolerated in rabbit eyes when administered by both intravitreal injection and vitrectomy infusion solution.

Animals↗

Intravitreal liposome-encapsulated trifluorothymidine in a rabbit model.

Two groups of albino rabbits received an intravitreal injection of liposome-encapsulated trifluorothymidine. One group underwent a clearance study using high-performance liquid chromatography. The results of this study demonstrated a prolonged vitreal drug level within the range of ID50 for many strains of herpesvirus and human cytomegalovirus (CMV) at 28 days after injection. The eyes of another group were evaluated with preoperative and postoperative indirect ophthalmoscopy, electroretinography, and histologic examination. No retinal toxicity was found.

Animals↗