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Biomedical subjects

K A Yates

Publications and source records attributed to K A Yates.

10 recordsLinked to original sources

Experimental laser-assisted in situ keratomileusis induces the reactivation of latent herpes simplex virus.

PURPOSE: We determined whether laser-assisted in situ keratomileusis acts as a trigger for the reactivation and ocular shedding of herpes simplex virus type-1 in a rabbit latency model. METHODS: Herpes simplex virus type-1 latently infected rabbits were divided into three treatment groups: Group I received surface excimer laser ablation in both eyes (positive control), Group II received laser-assisted in situ keratomileusis in both eyes, and Group III received no treatment (negative control). Eyes were cultured daily for 10 days to determine herpes simplex virus type-1 reactivation. RESULTS: The number of herpes simplex virus type-1 positive eye cultures and total herpes simplex virus type-1 shedding days were significantly greater after surface excimer laser ablation and laser-assisted in situ keratomileusis compared with the untreated control group (P < 0.002 and P < 0.000001, respectively). CONCLUSION: Laser-assisted in situ keratomileusis as well as surface excimer laser ablation act as a trigger for the reactivation of herpes simplex virus type-1 in the rabbit latency model.

Animals↗

Antiviral prophylaxis with twice daily topical cidofovir protects against challenge in the adenovirus type 5/New Zealand rabbit ocular model.

Adenoviral ocular infections are the most common external ocular infections world wide and there is no approved treatment. Topical cidofovir has been shown to be effective in vitro, in animal models and in case studies for the treatment of adenoviral ocular infections. Prophylaxis to prevent transmission within households and to reduce community epidemics remains an important public health goal. The current study examined whether antiviral prophylaxis with cidofovir, twice daily dosing, would restrict viral replication following a large challenge inoculum of adenovirus type 5 (Ad5) in the New Zealand white rabbit ocular model. The results showed that antiviral prophylaxis with 1 and 0.5% cidofovir significantly reduced mean daily Ad5 ocular titers (days 0-5), the number of Ad5 positive cultures/total (days 1-14), serial Ad5 positive cultures/total (days 1, 2, 3, 4, 5, 7), and the number of eyes with Ad5 replication beyond day 0 (1% cidofovir only). Antiviral prophylaxis appears to be an effective strategy to reduce and restrict adenovirus replication experimentally.

Adenoviridae Infections↗

Valacyclovir inhibition of recovery of ocular herpes simplex virus type 1 after experimental reactivation by laser in situ keratomileusis.

PURPOSE: To determine whether the systemic administration of valacyclovir (Valtrex) reduces ocular shedding of herpes simplex virus type 1 (HSV-1) after laser in situ keratomileusis (LASIK) in the New Zealand White (NZW) rabbit latency model. SETTING: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. METHODS: New Zealand White rabbits latently infected with HSV-1 W strain were divided into 3 groups. The first received 100 mg/kg/day of valacyclovir; the second, 200 mg/kg/day of valacyclovir; and the third (control), saline. One half the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with 1 dose before LASIK. The HSV-1 ocular shedding was determined from eye cultures for 7 days after LASIK. RESULTS: The administration of both 100 mg/kg/day and 200 mg/kg/day of valacyclovir significantly reduced the number of eyes (1/16 in both groups) and the total number of HSV-1 shedding days (1/122 and 2/122, respectively) from which HSV-1 was recovered compared to the control group (7/16 [P =.0396] and 14/129 [P <.007], respectively). CONCLUSIONS: Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding after LASIK in the NZW rabbit latency model. The clinical implications of this study suggest that patients with a history of recurrent ocular herpes may be able to safely have LASIK with less risk of a recurrent herpetic episode while on valacyclovir antiviral prophylaxis.

Acyclovir↗

Lomefloxacin is an effective treatment of experimental bacterial keratitis.

PURPOSE: Lomefloxacin was evaluated as a potential topical therapy for bacterial keratitis. METHODS: Lomefloxacin was compared with ciprofloxacin in different rabbit keratitis models. A total of 216 corneas were infected with Staphylococcus aureus (ciprofloxacin-susceptible and -resistant), Streptococcus viridans, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens and were treated with lomefloxacin (0.3%), ciprofloxacin (0.3% Ciloxan), and the control phosphate-buffered saline (PBS), respectively. The data were analyzed statistically comparing the decrease in the number of recovered viable bacteria. RESULTS: Compared with PBS-treated control corneas, the colony counts for all bacterial isolates were significantly reduced (p < 0.05) after topical treatment with either lomefloxacin or ciprofloxacin. For gram-positive bacteria, lomefloxacin and ciprofloxacin were equally effective. For gram-negative bacteria, lomefloxacin, while effective, was less so than ciprofloxacin under experimental conditions (p < 0.05). CONCLUSION: Our data, using multiple bacterial keratitis models, suggest that lomefloxacin is promising for therapy of bacterial keratitis. Further clinical studies are needed to expand its use for keratitis therapy.

Administration, Topical↗

Short-term treatment With a potent topical corticosteroid of an acute ocular adenoviral infection in the New Zealand white rabbit.

PURPOSE: To determine the effect of short-term topical therapy with 1% prednisolone acetate (PA) on normal immune adenoviral clearance in the rabbit ocular model. METHODS: Thirty rabbits were topically inoculated in both eyes with adenovirus type 5 (Ad5). On day 1, the rabbits were divided into three topical treatment groups: 1% PA four times daily for 3 days, 1% PA four times daily for 5 days, control (artificial tears) four times daily for 5 days. Eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. RESULTS: Compared with the control group, treatment with 1% PA for 3 or 5 days significantly increased the total and daily number of Ad5-positive cultures from days 7 to 14, prolonged the duration of Ad5 shedding, and increased the mean combined Ad5 titer from days 1 to 5. In addition, treatment with 1% PA for 5 days increased the mean combined Ad5 titer from days 7 to 14. CONCLUSION: Treatment of an ocular adenoviral infection with 1% PA for as little as four times daily for 3 days significantly enhanced adenoviral replication compared with the control group. Short-term corticosteroid treatment of acute adenoviral ocular infections with 1% PA should be used judiciously.

Acute Disease↗

The antiviral resistance and replication of cidofovir-resistant adenovirus variants in the New Zealand White rabbit ocular model.

PURPOSE: To determine the antiviral resistance of three cidofovir (CDV)-resistant variants of adenovirus type 5 (Ad5) and their ability to replicate in the New Zealand White rabbit ocular model. METHODS: Rabbits were inoculated topically in both eyes with the CDV-resistant variants R1, R2, and R3, and the Ad5 parental strain. On day 1, rabbits from each virus inoculation were divided into two topical treatment groups: 0.5% CDV and PBS control. Treatment was administered twice daily in both eyes for 7 days. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Using viral outcome parameters, CDV resistance was determined for each virus by comparing each CDV-treated virus group to its respective PBS control, and altered pathogenesis was assessed by comparing viral replication in the PBS control groups of the Ad5 parent and the three resistant variants. RESULTS: Topical 0.5% CDV treatment demonstrated significant antiviral inhibitory activity in the Ad5 parental group (e.g., reduced total Ad5-positive cultures, reduced daily Ad5-positive cultures on days 5, 9, 11, and 14, and duration of ocular shedding), but had no effect on the three CDV-resistant variants. There were no significant differences in pathogenicity between the Ad5 parent and the CDV-resistant variants. CONCLUSIONS: The Ad5 variants R1, R2, and R3 were resistant to topical treatment with 0.5% cidofovir in the rabbit ocular model. However, the acquisition of CDV resistance did not alter the replication of the three Ad5 CDV variants on the rabbit eye.

Adenoviridae Infections↗

Valacyclovir inhibits recovery of ocular HSV-1 after experimental reactivation by excimer laser keratectomy.

PURPOSE: The goal of this was to determine whether the systemic administration of valacyclovir (Valtrex) would reduce ocular shedding of herpes simplex virus 1 (HSV-1) after excimer laser ablation in the New Zealand rabbit latency model. METHODS: The in vitro 50% inhibitory concentration (IC50) of HSV-1 W strain was determined by using a plaque-reduction assay to verify its sensitivity to acyclovir. Forty-seven NZW rabbits latently infected with HSV-1 W strain were divided into four groups: I, 50 mg/kg/day valacyclovir; II, 100 mg/kg/day valacyclovir; III, 150 mg/kg/day valacyclovir; and IV, saline control. One half of the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with one dose before excimer laser keratectomy. HSV-1 ocular shedding was determined from eye cultures for 7 days after treatment. RESULTS: The IC50 for HSV-1 W was determined to be 2.9 microg/ml. The administration of both 100 mg/kg/day (group II) and 150 mg/kg/day (group III) of valacyclovir significantly reduced the number of eyes from which latent HSV-1 was recovered compared with the control group. There was no difference between the control group and group I (50 mg/kg/day valacyclovir). However, all three valacyclovir dosages significantly reduced the total number of HSV-1 shedding days compared with the control group, and 100% HSV-1 TG latency was demonstrated for all four groups. CONCLUSION: Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding in a dose-dependent manner after excimer laser keratectomy in the NZW rabbit latency model.

Acyclovir↗

Regeneration of an enchondroma defect under the influence of an implant of human bone morphogenetic protein.

A 29-year-old woman with an enchondroma that was expanding and eroding the palmar cortex of the middle phalanx was successfully treated by curettage and implantation of bone morphogenetic protein. The metaphysis and cortex were repaired by lamellar bone within 2 months. The medulla was completely filled with trabecular bone by 9 months. The full range of motion and normal functions of finger and hand joints were restored, and there was no recurrence or abnormalities at follow-up visits 2 1/2 years after the operation.

Adult↗

Scanning Raman spectroscopy for characterizing compositionally spread films.

Composition-spread La(1-x)SrxMnO3 thin films were prepared by pulsed laser deposition technique from LaMnO3 and SrMnO3 targets. The films were epitaxial with a continuous variation of the out-of-plane lattice parameter along the direction of composition gradient. Scanning Raman spectroscopy has been employed as a nondestructive tool to characterize the composition-spread films. Raman spectra showed the variation of the structural, Jahn Teller distortions and the presence of coexisting phases at particular compositions that are in agreement with the previous observation on the single-crystal samples. Raman spectra on the continuous composition-spread film also reveal the effect of disorder and strain on the compositions.

Spectrum Analysis, Raman↗