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Biomedical subjects

Y J Gordon

Publications and source records attributed to Y J Gordon.

At least 37 records · Page 2Linked to original sources

The survival of adenovirus in multidose bottles of topical fluorescein.

PURPOSE: To determine if common ocular adenovirus serotypes survive in vitro in multidose bottles of topical fluorescein (Fluress; Pilkington Barnes Hind, Inc, Sunnyvale, California). METHODS: Clinical isolates of adenovirus types 8 and 19 were inoculated separately into 10 bottles each of Fluress and maintained at room temperature (25 C). All bottles were titered for adenovirus on A549 cell monolayers at 0, 7, 14, 21, 28, and 49 days. RESULTS: Adenovirus was recovered from Fluress for up to 21 days for adenovirus type 19 and 28 days for adenovirus type 8. CONCLUSION: A multidose bottle of Fluress contaminated with adenovirus can be a potential source of adenoviral transmission in an ophthalmic office setting.

Adenovirus Infections, Human↗

Efficient reactivation of latent herpes simplex virus type 1 infection by excimer laser keratectomy in the experimental rabbit ocular model.

PURPOSE: To investigate the role of excimer laser keratectomy as a trigger for the reactivation of latent HSV type 1 (HSV-1) in the New Zealand rabbit ocular model. There are conflicting reports in the current literature about reactivation of HSV-1 after excimer laser photoablation. METHODS: New Zealand rabbits were inoculated topically with HSV-1 McKrae or W strain in each eye, and culture-positive dendritic keratitis was documented on day 7. After the establishment of latency (21+ days), animals were divided into three groups: group I animals underwent excimer laser photoablation in each eye; group II animals received intrastromal injections of sterile water to act as positive controls (a standard method); and group III animals received no treatment and represented spontaneous shedders. All eyes were swabbed daily from days 1 through 10 and plated on A549 cells. Recovery of HSV-1 on days 1 through 10 postinduction was analyzed to compare the efficiency of the different methods of viral reactivation. RESULTS: Reactivation of latent HSV-1 after excimer treatment was observed in nine (45%) of 20 eyes and was equivalent to the rate of reactivation seen in the positive control animals (eight [44.4%] of 18 eyes) (P=.99). Both of these rates were significantly greater than those of the untreated animals (one [5.6%] of 18 eyes) (P=.018). CONCLUSION: Excimer laser keratectomy appears to be an efficient trigger for the reactivation of latent HSV-1 in the New Zealand rabbit ocular model.

Animals↗

Multiple adenoviral serotypes demonstrate host range extension in the New Zealand rabbit ocular model.

PURPOSE: Although several human adenoviral serotypes demonstrated the genetic capability of replicating in New Zealand rabbit corneas in organ culture, only a single adenovirus (Ad) serotype, Ad5, has been reported to replicate in vivo in New Zealand rabbit eyes. The purpose of this study was to determine whether additional adenoviral serotypes could extend their host range to the New Zealand rabbit ocular model. METHODS: Six rabbits per viral isolate were inoculated in each eye after corneal scarification with 1.5 x 10(6) plaque-forming units per eye with one of the following reference or clinical adenovirus isolates: Ad1 ATCC, Ad1 Kmetz, Ad2 ATCC, Ad2 Wolf, Ad5 ATCC, Ad5 McEwen, Ad6 ATCC, Ad 19 ATCC, and Ad8 Cray (five rabbits). Eyes were cultured on days 0, 1, 3, 4, 5, 7, 9, 11, 14, 16, 18, and 21 after inoculation, and their tear film viral titers were determined on A549 cells. RESULTS: Ad19 ATCC and Ad8 Cray demonstrated no apparent viral replication. The mean duration of shedding was 1.5 and 0.3 days, respectively, and the total percentage of Ad-positive eyes was 13% and 3%, respectively. In contrast to Ad19 ATCC and Ad8 Cray, all other isolates demonstrated productive infection. The mean duration of shedding was 8 to 16 days (P < 0.0001), and the total percentage of Ad-positive eyes was 33% to 79% (P < 0.0002). The durations of shedding for Ad1 ATCC, Ad1 Kmetz, Ad2 ATCC, Ad2 Wolf, and Ad6 ATCC did not differ statistically from Ad5 McEwen, whereas Ad5 ATCC demonstrated a duration of shedding longer than all isolates (P < 0.0001). CONCLUSIONS: This was the first demonstration of host range extension by additional clinical and reference isolates of adenovirus types 1, 2, 5, and 6 in the New Zealand rabbit ocular model. These results suggested that host specificity was less stringent than previously thought.

Adenoviruses, Human↗

Comparison of ciprofloxacin and ofloxacin using human corneal susceptibility levels.

PURPOSE: We compared the in vitro susceptibility of gram-positive bacteria to ciprofloxacin and ofloxacin using human corneal susceptibility levels. METHODS: The concentrations of ciprofloxacin and ofloxacin that can be attained in 99% of human corneas (Cornea99) after topical administration were calculated statistically from reported data. The minimal inhibitory concentrations (MICs) were determined for 95 corneal isolates of gram-positive bacteria (51 Staphylococcus aureus, 16 Streptococcus pneumoniae, 16 Streptococcus viridans group, and 12 coagulase-negative staphylococci). Susceptibility was interpreted by comparing the MICs with the respective Cornea99 for each antibiotic. Time-kill studies of representative gram-positive bacteria were tested using the Cornea99 and the maximal corneal concentrations reported for ciprofloxacin and ofloxacin. RESULTS: The Cornea99 of ciprofloxacin and ofloxacin were calculated to be 3.57 microg/ml (n = 22) and 2.22 microg/ml (n = 20), respectively. The reported mean corneal concentrations of ciprofloxacin (6.90 +/- 6.20 microg/ml) and ofloxacin (5.71 +/- 6.15 microg/ml) were comparable (p = 0.54). All gram-positive bacteria were equally susceptible to ciprofloxacin and ofloxacin (p = 0.54) based on the Cornea99. The time-kill studies determined that 8-24 h were required for both ciprofloxacin and ofloxacin to reach bactericidal levels. CONCLUSION: Ciprofloxacin and ofloxacin demonstrated comparable penetration into the cornea and provided equivalent in vitro efficacy against representative gram-positive bacteria. Time-kill studies indicated that 8-24 h of continual corneal concentrations of ciprofloxacin and ofloxacin were necessary in this study to reduce susceptible gram-positive bacteria by 99.9%.

Anti-Infective Agents↗

Topical corticosteroids reverse the antiviral effect of topical cidofovir in the Ad5-inoculated New Zealand rabbit ocular model.

PURPOSE: To determine how the addition of topical corticosteroids would affect the anti-adenoviral inhibitory effect of topical cidofovir (S-HPMPC) in the Ad5 New Zealand (Ad5/NZ) rabbit ocular model. METHODS: In a series of experiments (two-eye design), Ad5-inoculated/NZ rabbits (10(6) pfu/eye) were treated with 1 of 3 treatment regimens. Group 1 was administered 1% cidofovir (CDV) twice a day for 3 days plus comfort tears four times a day for 14 days. Group 2 was administered 1% CDV twice a day for 3 days plus 1% Pred Forte four times a day for 14 days. Group 3 was administered vehicle twice a day for 3 days plus comfort tears four times a day for 14 days and served as the control. All eyes were evaluated for 21 days for serial eye titers, Ad5 positive eyes, and duration of Ad5 shedding. RESULTS: Compared to control eyes in the Ad5/NZ rabbit ocular model, CDV alone demonstrated a significant antiviral inhibitory effect: reduced mean Ad5 eye titer during the early phase of infection (days 3 to 7), fewer Ad5-positive eyes during the early and late (days 9 to 21) phases of infection, and shortened duration of shedding. However, concomitant treatment with both Pred Forte and CDV significantly reversed the antiviral inhibitory activity of CDV: increased mean Ad5 eye titer, increased Ad5-positive eyes (early and late phases) and prolonged duration of shedding. CONCLUSIONS: These experimental data further support the clinical development of cidofovoir as a topical antiviral agent, but they do not support a treatment regimen that includes a combination of topical corticosteroids and topical cidofovir as a desirable strategy for the treatment of symptomatic adenoviral ocular infection.

Adenovirus Infections, Human↗

The effects of corticosteroids of adenoviral replication.

OBJECTIVE: To evaluate the effects of Pred Forte (prednisolone acetate; Allergan Pharmaceutical, Irvine, Calif) on the replication of different adenoviral serotypes in vitro and in the adenovirus type 5/New Zealand rabbit ocular model. METHODS: The 50% inhibitory doses of Pred Forte and its components were determined for common ocular serotypes. The effects of continuous topical treatment with Pred Forte for 18 days were evaluated (eg, conjunctivitis, subepithelial immune infiltrates, and serial ocular viral titers) in the adenovirus 5/New Zealand rabbit ocular model. RESULTS: Pred Forte and prednisolone acetate inhibited adenoviruses 1, 5, 8, and 19 in vitro. In vivo, 1% Pred Forte significantly reduced conjunctivitis (P = .04) and subepithelial infiltrates (P = .02), but enhanced viral replication (P = .01) on days 9 to 21 and increased the duration of viral shedding (P < .001). CONCLUSIONS: Despite demonstrated anti-inflammatory and anti-immune effects, prolonged treatment of acute adenoviral infections with topical Pred Forte is not recommended because of the enhanced risks of viral transmission and community epidemics.

Adenoviridae Infections↗

Possible consequences of shaking hands with your patients with epidemic keratoconjunctivitis.

PURPOSE: We evaluated patients' hands as a possible vector for the spread of epidemic kerato-conjunctivitis. METHODS: The hands and conjunctivitis of 26 patients with epidemic keratoconjunctivitis and the hands of 26 uninfected control patients were cultured for infectious adenovirus. RESULTS: In 12 (46%) of 26 patients with epidemic keratoconjunctivitis, cultures from the hands were positive for adenovirus, whereas cultures from the hands of all uninfected control patients were negative. CONCLUSIONS: Simultaneous coinfection of patients' hands and eyes with adenovirus may contribute to office epidemics. Ophthalmologists and coworkers should not shake the hands of patients suspected of having epidemic keratoconjunctivitis unless properly gloved.

Adenovirus Infections, Human↗

Fluoroquinolones in the treatment of bacterial keratitis.

PURPOSE: We evaluated the potential role of three topical fluoroquinolones in the treatment of bacterial keratitis by means of a laboratory database. METHODS: Antibiotic susceptibilities were determined for 153 isolates from patients with bacterial keratitis. Results were analyzed for each fluoroquinolone individually and in combination with cefazolin. RESULTS: Predicted susceptibility to each cefazolin-fluoroquinolone combination (98.7%) was superior to that for single-agent therapy with ofloxacin (88.2%), ciprofloxacin (82.3%), or norfloxacin (80.4%) (P = .0002). A cefazolin-fluoroquinolone combination (98.7%) was comparable to a cefazolin-gentamicin combination (97.4%). CONCLUSIONS: Combination therapy with cefazolin and a fluoroquinolone offers a reasonable alternative for the treatment of bacterial keratitis. Single-agent therapy with fluoroquinolones for vision-threatening bacterial keratitis is not advised.

Anti-Bacterial Agents↗

A 5-year evaluation of the adenoclone test for the rapid diagnosis of adenovirus from conjunctival swabs.

The rapid diagnosis of adenoviral ocular infections affords the opportunity to limit the transmission of virus within the community and avoid expensive, unnecessary, and ineffective therapy. This study evaluated the results of a 5-year experience with the Adenoclone test (Cambridge Biotech, Worcester, MA), an enzyme immunoassay, applied directly to conjunctival swabs obtained from infected eyes. The sensitivity of this test was determined on 372 consecutive adenovirus culture-positive ocular specimens. A subset of 106 specimens was evaluated, including a retrospective chart review to determine the relationship between the Adenoclone result and the time to viral cytopathic effect (CPE) in A549 cell culture, ocular titers (90% tissue culture infectious dose; TCID90), serotype, and associated clinical parameters. Overall, the sensitivity for Adenoclone was 38% (142 of 372), which improved to 65% (129 of 199) for samples positive in culture during the first week. A positive Adenoclone test result was associated with a shorter time to CPE in cell culture (p = 0.0001). The mean ocular titers (log TCID90) associated with a positive test result were found to be at a significantly higher dilution than a negative result (-1.70 +/- 0.93 vs. -0.88 +/- 1.00, p < 0.0001). A positive Adenoclone outcome was independent of the serotype but directly associated with a recent visit to an ophthalmologist's office, follicular conjunctivitis, and conjunctival chemosis. For the rapid diagnosis of adenoviral ocular infections, the Adenoclone test remains useful, but a more sensitive test based on nonradioactive amplification is eagerly anticipated.

Adenoviridae↗

Isolation of human adenovirus type 5 variants resistant to the antiviral cidofovir.

PURPOSE: Cidofovir (S-HPMPC) is a potent broad-spectrum antiviral drug with potential clinical application against infections caused by human cytomegalovirus, herpes simplex virus, and adenovirus (AD). This study sought to determine whether variants of AD5 could be isolated in vitro that demonstrated increased resistance to this new antiviral drug. METHODS: Homogenous stocks of wild-type AD5 (ATCC strain VR-5) were generated from isolated plaques grown in A549 cells. The stocks subsequently were serially passaged in cells containing increasing levels (from 5 to 75 micrograms/ml) of cidofovir. The recovered virus either was passaged, titrated, or assayed for 50% inhibitory concentration (IC50) of cidofovir. RESULTS: Three independently isolated variants were obtained that demonstrated increased resistance to cidofovir. Viral resistance to the drug increased on stepwise passage in higher concentrations. Compared to the ATCC AD5 reference (IC50 = 6.2 micrograms/ml), stable cidofovir-resistant variants showed fivefold to eightfold resistance (AD5 RI IC50 = 36.5 micrograms/ml; AD5 R2 IC50 = 36.7 micrograms/ml; and AD5 R3 IC50 = 32.6 micrograms/ml; analysis of variance, P = 0.000001). However, a variable number of passages (1 to 13) at each concentration of cidofovir was performed to obtain robust infectious virus suitable for testing at the next higher concentration. All resistant virus isolates grew to levels of virus titer comparable to the parental virus and showed no apparent phenotypic changes in growth rates, plaque size, or efficiency of plaque formation. CONCLUSIONS: The successful isolation of AD5 variants in tissue culture resistant to cidofovir has important clinical implications with respect to the anticipated use of this antiviral drug in treating adenoviral ocular infections.

Adenoviruses, Human↗

Incidence of adenoviral and chlamydial coinfection in acute follicular conjunctivitis.

PURPOSE/METHODS: After we studied a case of chlamydial and adenoviral coinfection in a 20-year-old woman, we determined the incidence of chlamydial infection in patients with acute adenoviral conjunctivitis. In a randomized retrospective study, we evaluated 100 specimens of patients with culture-proven adenoviral conjunctivitis. RESULTS/CONCLUSIONS: Three of 100 (3%) specimens tested positive for chlamydial DNA using polymerase chain reaction. Adenoviral and chlamydial coinfection is rare, yet should be considered in patients with prolonged follicular keratoconjunctivitis.

Acute Disease↗

Evaluation of the Kodak Surecell Chlamydia test for the laboratory diagnosis of adult inclusion conjunctivitis.

PURPOSE: The Kodak Surecell Chlamydia test, a rapid enzyme immunoassay, has been reported to be highly sensitive (93%) and specific (96%) for detecting chlamydial lipopolysaccharide antigen in conjunctival specimens from infants, but has not been evaluated previously in adult conjunctival specimens. This study was designed to determine the efficacy of the Kodak Surecell Chlamydia test for the laboratory diagnosis of adult inclusion conjunctivitis. METHODS: Twenty Chlamydia culture-positive conjunctival specimens from adults (true-positives) and 20 true-negative specimens were tested with the Kodak Surecell Chlamydia test. RESULTS: The Kodak Surecell Chlamydia test was 40% (8/20) sensitive, 100% (20/20) specific, and 70% (28/40) efficient. CONCLUSIONS: This study indicates that the Kodak Surecell Chlamydia test, though highly specific, is less sensitive in its ability to diagnose chlamydial conjunctivitis in adults than has been reported previously in infants.

Adult↗

Evaluation of the polymerase chain reaction test for detecting chlamydial DNA in adult chlamydial conjunctivitis.

PURPOSE: A new polymerase chain reaction (PCR) test (Amplicor, Diagnostics, Branchburg, NJ) was evaluated for its ability to detect chlamydial DNA from previously obtained adult conjunctival specimens. METHODS: The sensitivity of this PCR test was determined on 42 adult conjunctival specimens that were culture-positive for Chlamydia. The specificity was determined by testing 40 true-negative specimens that included 10 normal conjunctival samples and 20 ocular specimens that were culture-positive for herpes simplex virus or adenovirus. The remaining ten samples consisted of ocular bacterial pathogens in chlamydial transport media. RESULTS: Amplicor was 88% (37/42) sensitive and 100% (40/40) specific. CONCLUSIONS: The authors conclude that PCR testing for chlamydial DNA from ocular specimens may be useful, especially when conditions in transport might reduce the yield of positive cultures.

Adenovirus Infections, Human↗

An in vitro comparison of the susceptibilities of bacterial isolates from patients with conjunctivitis and blepharitis to newer and established topical antibiotics.

This retrospective study compared new and established topical antibiotics with regard to the in vitro susceptibility of bacterial isolates recovered from patients with conjunctivitis (n = 385) and blepharitis (n = 173) using the National Committee for Clinical Laboratory Standards-approved disk diffusion method. The percent susceptibility of recovered isolates to single antibiotic agents or combinations were ranked from greatest to least: chloramphenicol, bacitracin/polymyxin B, ofloxacin, sulfa, ciprofloxacin, trimethoprim/polymyxin B, norfloxacin, gentamicin, bacitracin, trimethoprim, tobramycin, neomycin, erythromycin, and polymyxin B. We determined that none of the available topical antibiotics provided 100% broad spectrum coverage in vitro. Established antibiotics often provided coverage comparable to the newer drugs. Due to the unproven value of in vitro testing as a predictor of clinical outcome in bacterial blepharitis and conjunctivitis, the ophthalmologist should choose therapy based on clinical experience, ongoing critical evaluation of available antibiotics, and cost-effectiveness.

Administration, Topical↗

Adenoviral ocular isolates demonstrate serotype-dependent differences in in vitro infectivity titers and clinical course.

The purpose of this study was to evaluate clinical ocular adenoviral isolates for differences among and within serotypes with respect to in vitro infectivity titers and clinical course. The study design included a retrospective chart review and the determination of in vitro infectivity titers (TCID90s) of 90 clinical ocular isolates of various adenoviral serotypes. Adenovirus serotype 8 (AD8) was recovered in significantly greater numbers of patients in the second week of infection compared to all other serotypes (p < 0.002). AD3 and AD4 presented with the highest infectivity titers during the first week of acute infection. Up to 4 logs of variation was demonstrated in TCID90s among isolates of the same serotype. Among the clinical parameters studied, eyelid edema was significantly more common among AD8-infected patients as compared to all other serotypes (p < 0.04). For the first time, specific, but limited serotype differences with respect to infectivity titers and clinical course were demonstrated for adenoviral ocular isolates. Important variations in isolate virulence within a given serotype were also observed.

Adenovirus Infections, Human↗

Chlamydia trachomatis can be transmitted by a nonporous plastic surface in vitro.

Chlamydial conjunctivitis is a disease associated with venereal transmission through direct sexual contact or autoinoculation with genital secretions. Appropriate therapy for patients and their sexual partners involves important questions regarding the source of infection and mode of transmission. This study explored the potential role of a fomite, i.e., an environmental surface, as a possible vector of transmission. We determined the in vitro recovery of Chlamydia trachomatis from a nonporous plastic surface under ambient and humid conditions using the standard shell vial technique and confirmation by direct monoclonal immunofluorescence. Under ambient conditions, the TP50 (time at which 50% of samples were positive for Chlamydia) was 5 min, with complete desiccation occurring at 45 min. Under humid conditions, the TP50 was 52.5 min and complete desiccation did not occur up to 3 h. Beyond 45 min, a significantly greater number of positive chlamydial samples were collected under humid conditions (11 of 30) than under ambient conditions (0 of 30) (p = 0.00016). We conclude that a fomite, such as a nonporous plastic surface, may serve as a potential vector for the transmission of chlamydial infection to the eye, especially under humid conditions. This new information may prove useful in counseling patients and their sexual partners.

Chlamydia trachomatis↗