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Biomedical subjects

Y J Gordon

Publications and source records attributed to Y J Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1994

Comparative tear concentrations over time of ofloxacin and tobramycin in human eyes.

The pharmacokinetic profiles of 0.3% ofloxacin and 0.3% tobramycin ophthalmic solutions after multiple administrations in the eyes of 160 healthy volunteers were evaluated. In human tears, ofloxacin and tobramycin were found to have terminal half-lives of 226 and 154 minutes, respectively. The mean residence time in the ocular tear fluid was 326 minutes for ofloxacin and 106 minutes for tobramycin. The mean duration of time that ofloxacin remained above the MIC90 value for five bacterial species evaluated was 605 minutes, compared with 251 minutes for tobramycin. The mean area under the inhibitory curve for the five bacterial species evaluated was greater for ofloxacin (2224) compared with tobramycin (1549). The duration of time above the MIC90 for ofloxacin was longer compared with tobramycin for gram-positive isolates. Overall, the pharmacokinetic and pharmacodynamic profiles of ofloxacin were superior to those of tobramycin for most parameters studied.

Adolescent↗
PubMed1994

HPMPC, a broad-spectrum topical antiviral agent, inhibits herpes simplex virus type 1 replication and promotes healing of dendritic keratitis in the New Zealand rabbit ocular model.

Previously, we demonstrated that HPMPC, a new, broad-spectrum antiviral agent, inhibited adenovirus type 5 in the New Zealand (NZ) rabbit ocular model (Cornea 1992; 11:529-33). Historically, no antiviral agent has been demonstrated to be effective against both herpes simplex virus type 1 (HSV-1) and adenovirus eye infections in an experimental animal model. In this study, we compared topical 0.2% HPMPC to 1% trifluridine and vehicle control in the NZ rabbit HSV-1 keratitis model. Using a double-masked, two-eye design, NZ rabbits were inoculated in both eyes with HSV-1 W strain (10(5) pfu/eye), and dendritic keratitis and HSV-1 ocular titers were measured serially. Compared with the control group, both topical 0.2% HPMPC and 1% trifluridine significantly reduced healing time of HSV-1 dendritic keratitis, lowered HSV-1 ocular titers on days 3 through 11, and shortened duration of HSV-1 shedding in the tear film. For all outcome parameters measured, topical 0.2% HPMPC was as effective as 1% trifluridine. A new concept of a broad-spectrum topical antiviral agent was shown to be effective against HSV-1 in an NZ rabbit keratitis model, and further development toward clinical application appears desirable.

Administration, Topical↗
PubMed1994

Use of polymerase chain amplification reaction for the detection of adenoviruses in ocular swab specimens.

PURPOSE: To evaluate the application of polymerase chain reaction (PCR) methodology as a potential diagnostic tool for the detection of adenovirus DNA in ocular swab samples. METHODS: Oligonucleotides derived from the adenovirus hexon gene were used to amplify a 306-base pair (bp) product by PCR. Radiolabeled oligonucleotides derived from sequences within the amplified product were used as specific probes. Specificity was determined against DNA of 13 adenovirus serotypes (types 1 to 11, inclusive, and types 19 and 37) and from nonadenoviral DNAs. Limits of detection were determined by PCR amplification of known amounts of purified adenovirus serotype 2 DNA. The assay was tested on 107 ocular swab samples and correlated to results obtained from tissue culture and a commercial immunoassay (Adenoclone). RESULTS: The 306-bp PCR product was amplified from all adenovirus serotypes tested, but not from negative control DNAs. As little as 15 fg of adenovirus type 2 DNA could be detected by PCR and ethidium bromide stain. Using a simplified sample preparation procedure, 46 of 58 adenovirus culture-positive but Adenoclone-negative swabs were positive by PCR (79% sensitivity). All (11 of 11) Adenoclone-positive clinical eye swabs tested were positive by PCR (100% sensitivity). Only 1 of 38 nonadenoviral ocular swab samples was positive by PCR (97% specificity). CONCLUSIONS: PCR appeared to be highly suitable for the diagnosis of adenovirus in ocular swabs, offering important improvements in speed over tissue culture isolation and in sensitivity over immunoassay.

Acute Disease↗
PubMed1994

Topical HPMPC inhibits adenovirus type 5 in the New Zealand rabbit ocular replication model.

PURPOSE: To evaluate the antiviral inhibitory activity of HPMPC against ocular adenoviral serotypes in vitro and to determine the therapeutic efficacy and ocular toxicity of treatment with topical HPMPC on established adenovirus type 5 (AD5) McEwen infection in the New Zealand (NZ) rabbit ocular replication model. METHODS: The 50% inhibitory dose (ID50) of HPMPC was determined for various clinical isolates of AD5 and AD8 by plaque assay in A549 cells. In vivo inhibitory effects were measured by serial ocular titers and duration of viral shedding in the AD5-NZ rabbit ocular model. Local ocular toxicity was evaluated by external and slit lamp examination for blepharitis, conjunctivitis, keratitis, and iritis. RESULTS: The mean ID50 for seven isolates of AD8 was 0.47 (range, 0.02 microgram/ml to 0.82 microgram/ml), and the mean ID50 for seven isolates of AD5 was 1.03 (range, 0.15 microgram/ml to 2.80 micrograms/ml). In a series of in vivo experiments, topical administration of HPMPC for as long as 10 days (total dose, > 2.8 mg) significantly reduced both AD5 ocular titers and the number of days of viral shedding compared to that for vehicle-treated control eyes. Local ocular toxicity was not clinically significant at a total dose of < 10 mg administered for as long as 10 days. CONCLUSIONS: HPMPC, a broad-spectrum, long-acting nucleoside monophosphate analog, is a promising candidate for the treatment of epidemic keratoconjunctivitis infections. Further studies to ensure safety and efficacy in humans are warranted.

Adenoviridae Infections↗
PubMed1993

Prolonged recovery of desiccated adenoviral serotypes 5, 8, and 19 from plastic and metal surfaces in vitro.

BACKGROUND: Prevention of the spread of epidemic keratoconjunctivitis (EKC) at eye care facilities (doctors' offices, clinics, hospitals) has been a major public health goal for ophthalmology for more than 50 years. The authors explored a potentially contributing attribute of the adenovirus serotypes that cause EKC. Specifically, they investigated the capacity of different clinical and laboratory ocular serotypes (AD8, 19, and 5) to survive for extended periods of time in a desiccated state. METHODS: Twenty microliters containing 2000 plaque-forming units of different ATCC laboratory adenoviral ocular serotypes (AD8, 19, and 5) and clinical isolates (AD8 Cray, AD19 Kowalski, and AD5 McEwen) were inoculated onto 7-mm plastic disks and 6-mm aluminum foil disks and were allowed to completely desiccate. At weekly intervals up to 7 weeks, eight desiccated virus-inoculated plastic or metal disks per serotype were added to tissue culture medium, and the amount of recoverable virus was determined by plaque assay on A549 cells. RESULTS: Ocular adenoviral serotypes AD8, 19, and 5 could be recovered up to 49 days from plastic, and 35 to 49 days from metal. Sufficient virus concentrations (> 100 plaque-forming units/disk) to be clinically infectious were recovered up to 28 days. Differences in recovery among serotypes (AD19 > AD5, AD8) were demonstrated, but laboratory and clinical isolates of the same serotype were usually comparable. CONCLUSIONS: Ocular isolates of adenovirus that cause EKC are much harder than previously suspected, and the capacity to survive in a desiccated state may possibly play some role in office-based mini-epidemics of EKC.

Adenoviruses, Human↗
PubMed1993

A comparison of enzyme immunoassay and polymerase chain reaction with the clinical examination for diagnosing ocular herpetic disease.

PURPOSE: The results of two laboratory diagnostic herpes simplex virus (HSV) tests, an enzyme immunoassay (improved Herpchek [iHC]) and the polymerase chain reaction (PCR), were compared with the clinical examination in the diagnosis of HSV. We determined when diagnostic laboratory tests provided the initial diagnosis of HSV ocular disease and when they were only confirmatory. METHODS: The sensitivity and specificity of iHC and PCR were determined using 22 HSV culture-positive clinical samples, 10 adenovirus culture-positive clinical samples, 5 samples from normal conjunctivas, 4 bacterial samples, and 1 sample containing Varicella zoster virus. The medical history of the 22 patients with positive HSV cultures were reviewed to determine the initial diagnosis by clinical examination and the initial therapy. RESULTS: For typical presentations of ocular HSV disease, the clinical examination is as accurate as iHC (P = 0.99) and PCR (P = 0.24). However, for atypical presentations of ocular HSV disease, iHC (P = 0.000005) or PCR (P = 0.00006) were more accurate in detecting HSV infection than the clinical examination. CONCLUSION: Laboratory diagnosis of HSV from ocular samples was most useful to the clinician in atypical presentations of herpetic ocular disease.

Antigens, Viral↗
PubMed1993

Recruitment and screening experience for a clinical trial involving tear concentrations of a new drug.

The process of recruitment and screening of volunteers for clinical research studies has not been thoroughly evaluated in the ophthalmic literature. The data for the current report were derived from a double-masked randomized clinical trial designed to evaluate and compare the effective tear level concentrations of three topical ophthalmic medications. Subjects were recruited from the general population and were healthy volunteers on no medications. Tear volume was measured by the Schirmer test with anesthesia; acceptable results were in the range of 10-25 mm/5 min. Study enrollment was limited to 32 subjects per week, with a total sample size goal of 320. The study population, 18-45 years of age, consisted primarily of white male college students. Nine hundred fifty-seven volunteers were recruited. Of the 498 of these subjects that reported for screening (52%), 459 (48%) were actually screened, and 320 (33%) were enrolled. The overall prevalence of an abnormal Schirmer test (< 10 or > 25 mm/5 min in either eye) in the screened population was 22%. The frequency of decreased tear production (13%) was slightly greater than that of increased tear production (9%). An abnormal Schirmer test was the primary reason for ineligibility. The completion rate for those enrolled was 96%. This type of information is valuable when designing a clinical trial, especially with regard to budgetary, time table, and sample size estimations.

Adolescent↗
PubMed1993

Rapid diagnostic tests for infectious ocular disease.

There is a current and ongoing need for the rapid, accurate diagnosis of ocular infection and the prompt initiation of appropriate therapy to prevent visual loss, maximize use of health care resources, and reduce physicians' medicolegal liability. For the busy clinician, and ideal rapid diagnostic test to determine ocular pathogens would be one whose result is available before the patient leaves the doctor's office, so that optimal treatment can be promptly instituted. Today, the major rapid diagnostic tests available to the busy clinician are the clinical examination and the stained microscopical smear of conjunctival and corneal specimens. The latter technique is grossly underutilized and would contribute significantly to improved accuracy in early diagnosis of ocular infections. In the near future, improved enzyme immunoassays and simplified PCR kits will provide for highly sensitive and specific diagnostic capabilities for detecting ocular pathogens in the laboratory and, possibly, office settings.

Clinical Laboratory Techniques↗
PubMed1992

Pretreatment with topical 0.1% (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine inhibits adenovirus type 5 replication in the New Zealand rabbit ocular model.

Currently there is no clinically effective antiviral agent for the prevention or treatment of ocular adenoviral infections. Using a paired-eye, masked design, we tested the antiviral efficacy of topical 0.1% (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine in the New Zealand rabbit ocular model after topical and intrastromal inoculation with 100 microliters (4 x 10(5) plaque-forming units per eye) of adenovirus type 5 McEwen, a clinical isolate. Prevention studies involved pretreatment (six times a day) 1 day before inoculation and continuing for 4 additional days. Compared with the control eyes, the pretreated eyes showed a significant reduction in the peak viral eye titers on days 3, 4, 5, and 7 after treatment (p < 0.03-0.005), and a reduction in the duration of viral sheeding (p < 0.02). Rebound increase in adenoviral titers was detected in five of 20 eyes (25%) after cessation of treatment, suggesting a therapeutic effect and a need for further studies to optimize the treatment regimen.

Adenoviridae↗
PubMed1992

An ocular model of adenovirus type 5 infection in the NZ rabbit.

Ocular adenoviral infections occur worldwide, and currently, there is no ocular animal model for evaluating new antivirals or studying pathogenesis. With a paired-eye design, an ocular model was developed in 32 New Zealand rabbits following topical and intrastromal inoculation with a clinical isolate of adenovirus type 5 (Ad5 McEwen). Clinical signs of infection--conjunctivitis, corneal edema, subepithelial infiltrates, and iritis--and seroconversion were evaluated. Replicating virus on the ocular surface was determined by serial ocular titers. Reproducible acute ocular infection was demonstrated in 32 of 32 infected eyes (100%), with mean viral replication lasting for 8.3 days. Peak ocular viral titers (10(3) plaque forming units/ml) were achieved on day three after inoculation and represented a 2 log increase (100 times) over day one. Ocular viral replication was associated with acute conjunctivitis (24/34 eyes, 75%), and delayed-onset presumed immune-mediated clinical disease was associated with: blepharoconjunctivitis (21/32 eyes, 66%), iritis (29/32 eyes, 91%), corneal edema (32/32 eyes, 100%), and subepithelial corneal infiltrates (30/32 eyes, 94%). Seroconversion was demonstrated in 26 of 31 rabbits (84%). The study concludes that a potentially useful animal model of adenoviral ocular infection can be attained.

Adenoviridae Infections↗
PubMed1991

Inhibitory effect of (S)-HPMPC, (S)-HPMPA, and 2'-nor-cyclic GMP on clinical ocular adenoviral isolates is serotype-dependent in vitro.

Currently, there is no effective treatment for ocular adenoviral infections that occur in epidemics worldwide, produce significant patient morbidity, and cause substantial economic losses. We tested several new antivirals in vitro, and found that (S)-HPMPC, (S)-HPMPA, and 2'-nor-cyclic GMP demonstrated significant serotype-dependent inhibitory activity by plaque reduction assay (ID50 = 0.017-17.0 micrograms/ml) against common clinical ocular isolates and standard adenoviral serotypes (Ad 1, Ad 5, Ad 8, and Ad 19). (S)-HPMPC was the least toxic (CD50 in A549 cells = 306 micrograms/ml), and (S)-HPMPC and (S)-HPMPA had high selectivity indices.

Adenine↗
PubMed1991

Replication of ocular isolates of human adenovirus is serotype-dependent in rabbit corneal organ culture.

The goal of the present in vitro study was to determine the ability of unadapted human adenoviral ocular isolates to replicate in the rabbit cornea. Rabbit corneas grown in organ culture (24 well plate) were inoculated topically with 50 microliters (5 x 10(5) pfu) of different ocular adenoviral serotypes (ATCC and clinical isolates). Control wells (no cornea present) were inoculated in a similar fashion. Viral replication was determined by serial aliquots titrated on A549 cells. We demonstrated sustained viral replication over time of all isolates (100%) of Ad1, 2, 5, 6, 8, 9, 11 and 37 tested. No isolates (0%) of Ad3, 7A, 19, and 4 demonstrated replication in our model. Peak titers varied among successful serotypes from 10(2) pfu/ml (Ad11) to 10(5) PFU/ml (Ad5), and among different isolates of a given serotype. We conclude that the ability of unadapted human Ad serotypes to replicate in rabbit corneas was serotype-dependent, and that subgroup C (Ad1, 2, 5, and 6) appeared to be the most successful subgroup.

Adenoviruses, Human↗
PubMed1990

Host species and strain differences affect the ability of an HSV-1 ICP0 deletion mutant to establish latency and spontaneously reactivate in vivo.

HSV-1 latency and reactivation were studied in vivo by spontaneous and iontophoresis-induced ocular viral shedding in New Zealand rabbits, Balb/c and A/J mice latently infected with wild-type KOS, and dl x 3.1, a progeny ICP0 deletion mutant. The presence of trigeminal ganglionic latency was demonstrated by the in vitro methods of cocultivation and in situ hybridization. Although the efficiency of ganglionic latency was significantly less (P less than .0001) for dl x 3.1 than for KOS in both mice and rabbits, only dl x 3.1 shed spontaneously in the NZ rabbit. Iontophoresis of adrenergic agents failed to induce reactivation and ocular viral shedding of KOS or dl x 3.1 in mice or rabbits. The establishment of latency and reactivation of KOS and dl x 3.1 was dependent on the host animal. We conclude that host factors as exemplified by host species and host strain differences significantly affected the ability of KOS and dl x 3.1 to establish latency, to reactivate, and to shed spontaneously. ICP0 expression was not required for the establishment or maintenance of latency, nor was it required for the reactivation of latent HSV-1. Furthermore, the biological activity of KOS and dl x 3.1 during latency in vivo did not correlate with latency studies based on in vitro methods.

Animals↗
PubMed1990

Prolonged recoverability of desiccated adenovirus type 19 from various surfaces.

Epidemic keratoconjunctivitis is a highly contagious disease whose transmission has been linked to the ophthalmologist's office. The authors studied the ability of adenovirus 19 (ADV 19) to survive on surfaces commonly found in the office setting. An initial in vitro laboratory experiment demonstrated that ADV 19 in a desiccated state could be recovered up to 8 days from paper, and up to 10 days from cloth, metal, and plastic. The amount of recovered ADV 19 was significantly greater (analysis of variance, P less than 0.0001) from nonporous surfaces (plastic, metal) compared with porous surfaces (cloth, paper). A second experiment demonstrated that 35 days was the maximum length of time that desiccated ADV 19 could be recovered from a nonporous surface (plastic). The authors conclude that despite drying, ADV 19 is a hearty virus that remains potentially infectious for a long time on various surfaces that may be found in an ophthalmologist's office.

Adenoviruses, Human↗
PubMed1990

The effect of alpha blockade on iontophoresis-induced ocular shedding of latent HSV-1 W in different host animals.

Previous studies demonstrated that non-specific beta blockade promoted ocular shedding of latent HSV-1 in the mouse and rabbit iontophoresis models. The present study examined the effect of topical alpha blockers, thymoxamine and corynanthine, on reactivation and induced ocular shedding of latent HSV-1 W in different host animals. Latent trigeminal ganglionic infection was established in Balb/c mice and New Zealand rabbits following corneal inoculation with HSV-1 W strain, and later confirmed by co-cultivation. Treatment with coded eye drops (thymoxamine, corynanthine or BSS was begun one day prior to iontophoresis induction and continued BID OU for 5 days. Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, and characteristic HSV-1 cytopathic effect in Vero cells. In Balb/c mice, topical administration of thymoxamine 0.5% or corynanthine 5% significantly reduced the number of virus-positive eyes, virus-positive mice, and total virus-positive swabs per experiment, whereas the inhibitory effect was minimal in NZ rabbits. We conclude that alpha blockade may alter the reactivation signal that is mediated via the adrenergic system, and that different host factors (as expressed in different species) may play an important role in this process.

Administration, Topical↗
PubMed1990

Vanadate promotes reactivation and iontophoresis-induced ocular shedding of latent HSV-1 W in different host animals.

Vanadate is a potent inhibitor of calcium stimulated ATPase, Na, K-ATPase, and may have adrenergic activity. Using the iontophoresis method, we compared vanadate to a BSS control and the standard iontophoresis model (6-hydroxydopamine/epinephrine) by measuring induced ocular shedding of latent HSV-1 in different host animals. Latent trigeminal ganglionic infections were established in Balb/c mice and New Zealand rabbits following corneal inoculation with HSV-1 [W] strain, and later confirmed by cocultivation. Latently-infected animals (greater than 1 month post-infection) were divided into three treatment groups. Each group was iontophoresed with BSS, vanadate 1% or 6-HD 1%, and then treated topically for 10 days with BSS, vanadate or epinephrine respectively. Reactivation and recovery of latent HSV-1 was detected by daily ocular swabbing, plating, and observing progressive viral growth in Vero cells. The vanadate group had more virus-positive eyes than the BSS control group in mice, (8/32 vs. 1/32 P less than .01), and also in rabbits (14/20 vs 6/22 P less than .01). Virus-positive animals and total positive swabs were also higher for vanadate than BSS in both mice and rabbits. Furthermore, while vanadate was associated with fewer virus-positive eyes than 6-HD & EPI (8/32 vs. 17/32 P less than .02) in mice, there were no significant differences in rabbits. We conclude that vanadate promotes ocular shedding of latent HSV-1, and may act through an adrenergic mechanism.

Animals↗