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Biomedical subjects

Y J Gordon

Publications and source records attributed to Y J Gordon.

90 records · Page 5Linked to original sources

Co-cultivation versus blot hybridization for the detection of trigeminal ganglionic latency following corneal inoculation with HSV-1 strains of varying TK expression and pathogenicity.

The sensitivity of two methods for the detection of latent trigeminal ganglionic (TG) infections were compared: (1) co-cultivation which detects infectious virions, and (2) blot hybridization which detects HSV-1 DNA sequences. Adult New Zealand rabbits were inoculated following corneal scarification with three strains of HSV-1 which differed in their thymidine kinase expression, and in their ability to invade the CNS and establish latency. When a large volume load of latent TG virus was expected (NIH TK+ strain), co-cultivation and blot hybridization were equally effective in detecting latent virus. However, when a small volume load of latent virus was expected (NIH TK+/-, NIH TK-), co-cultivation with its inherent amplification proved superior to blot hybridization for the detection of latent virus.

Animals↗

Immunosuppression promotes ocular virus replication and CNS neurovirulence following corneal inoculation with an avirulent herpes simplex type 1 thymidine kinase negative mutant.

The present study determined the effect of immunosuppression on the pathogenicity of an avirulent HSV-1 thymidine kinase negative mutant in the murine model. Following corneal inoculation with an HSV-1 TK- mutant, normal and cyclophosphamide-immunosuppressed outbred mice were evaluated for keratitis, ocular, trigeminal ganglia, and forebrain virus titers, survival, and latency. Immunosuppression enhanced virus pathogenicity producing greater keratitis, higher ocular, trigeminal, and forebrain virus titers, decreased survival, and increased trigeminal ganglionic residual infectious virus and latency. Our results suggest that both normal host defenses as well as the virus thymidine kinase expression contribute to HSV-1 pathogenicity.

Animals↗

The role of herpesvirus type 1 thymidine kinase in experimental ocular infections.

Herpesvirus type 1 thymidine-kinase-negative mutants are readily selected for in tissue culture and in humans by acyclovir, a promising antiviral agent. We investigated the ocular pathogenicity of thymidine-kinase-negative mutants in the rabbit. The natural course of untreated keratitis induced by the herpesvirus type 1 thymidine-kinase-negative strain was characterized by superficial dendrites and geographic ulcers that healed spontaneously without loss of corneal clarity. We also studied the relationship between herpesvirus type 1 thymidine-kinase activity and virulence in the rabbit with three strains of herpesvirus type 1: NIH thymidine-kinase-positive (100% thymidine-kinase activity), NIH thymidine-kinase-intermediate (25% thymidine-kinase activity), and NIH thymidine-kinase-negative (0% thymidine-kinase activity). Despite comparable ocular titers, the NIH thymidine-kinase-positive strain proved to be the most virulent, causing significantly (P less than .002) more keratitis, encephalitis, and death than the other strains.

Animals↗

HSV-1 thymidine kinase promotes virulence and latency in the mouse.

The relationship between thymidine kinase (TK) activity and virulence was studied in the mouse using three HSV-1 strains: (1) NIH TK+ (100% activity), (2) NIH TK+/- (25% TK activity), and (3) NIH TK- (0% TK activity). Following corneal inoculation, keratitis, virus titers (eye, trigeminal ganglia brain), survival, and latency were determined for each strain. The most virulent strain, NIH TK+ (30% survival) produced the worst keratitis, highest CNS titers, and established latency in 78% of surviving mice. NIH TK+/- demonstrated dose-dependent intermediate virulence (57-90% survival) and established latency in 80% of mice. NIH TK-, the most avirulent strain (93-100% survival) produced eye virus titers equal to the other strains but did not appear to invade the CNS or establish latency. These results indicate that TK gene activity is essential for HSV-1 murine neurovirulence (ie, efficient CNS invasion, replication and establishment of latency), but not for ocular replication.

Animals↗

Pediatric ocular injuries in Lesotho.

One hundred and ten children were evaluated in a prospective study in Lesotho to determine the pattern of pediatric ocular injuries in a developing African country. The pattern was found to be the same as that of developed countries regarding increased incidence in boys, frequency of accidental, self-inflicted and assault injuries, and high incidence of corneal lacerations, traumatic cataracts, hyphemas, and lid lacerations. The pattern differed from developed countries in the absence of injuries due to arrows, airgun pellets (BBs), fireworks, toys and chemical burns, the absence of orbital fractures, intra-ocular metallic foreign bodies, and rarity of retinal detachment, and the generally poor visual results following perforating ocular injuries. An information campaign is advocated in Lesotho to aid in the prevention of pediatric ocular injuries.

Adolescent↗

Screening of pre-school and school children for ocular anomalies in Lesotho.

One thousand two hundred and ninety-six pre-school and school children were examined in the first screening programme for ocular anomalies in Maseru, Lesotho. One hundred and eighteen children (8.9%) were found to have significant ocular anomalies requiring treatment. The most common anomalies included refractive errors, squint, convergence insufficiency, amblyopia, vernalis, lid abnormalities, leukoma cornea, and cataract. The importance of school screening for ocular anomalies in a developing African nation is emphasized.

Child↗

Adult ocular injuries in Lesotho.

Two hundred and fifty-two adults were evaluated in a prospective study in Lesotho to determine the pattern of ocular injuries in a developing African country. The pattern was found to be similar to that of developed countries regarding increased incidence in young males, high frequency of assault injuries, and high incidence of lacerations to lids, cornea and sclera. The pattern differed from developed countries in the low incidence of perforating ocular injuries associated with occupation, motor vehicles and sports, the absence of orbital fractures, metallic intra-ocular foreign bodies, the low incidence of retinal detachment, and the generally poor visual results following perforating ocular injuries. Additional ophthalmic facilities with improved medical transportation is advocated in Lesotho to improve the visual prognosis in ocular injuries.

Adolescent↗

Diabetic retinopathy in Lesotho.

Diabetic retinopathy was found in 47.8% of 153 consecutive diabetic clinic patients examined in Maseru, Lesotho. Background retinopathy was present in 78% of patients with retinopathy, compared with 22% with proliferative changes. While no difference in prevalence of diabetic retinopathy could be demonstrated between the sexes, an association between diabetic retinopathy and hypertension and peripheral neuropathy was observed. The prevalence and severity of diabetic retinopathy was significantly related to the duration of disease. The pitfalls inherent in comparing the results of the current study with other published reports are considered. Better epidemiological surveys are required to determine the true prevalence of diabetic retinopathy among different racial, ethnic, religious, and tribal groups in Africa.

Adolescent↗

Incidence of epibulbar tumors in lesotho.

A series of 18 epibulbar tumors are reported from Lesotho, a nontropical African country. The etiologic risk factors in epibulbar tumors are evaluated in termas of the environmental conditions present in Lesotho. The pathogenesis of epibulbar tumors is discussed in terms of histological progression from benign to malignant lesions following prolonged exposure to presumed etiologic risk factors.

Adult↗

Survey of ophthalmic conditions in rural Lesotho.

The first survey of ocular problems in rural Lesotho was conducted by a visiting eye team and consisted of an examination of 1266 ophthalmic clinic patients at 15 representative sites throughout the country. The most common ocular conditions encountered were: conjunctivitis, refractive error, vernalis, senile cataract, glaucoma, corneal opacities and trauma. This disease pattern differs from most developing African nations for reasons of climate, geography and diet. The absence of disciform macular degeneration, narrow-angle glaucoma, and rarity of retinal detachment was noted. The educational impact of the survey, and its importance for future planning are suggested.

Adolescent↗

Multiple regression analysis predictor models in exotropia surgery.

We developed a statistical model based on multiple regression analysis from a sample population of 30 patients with intermittent exotropia who underwent bilateral recession of the lateral recti muscles. We also identified predictor variables, which accounted for most of the change in deviation per millimeter of surgery performed. The application of multiple regression analysis to the problem of exotropia may be limited by variation in predictor variables according to sample population, multicollinearity, measurement unreliability, and the unproven assumption that the preoperative calculation of effect per millimeter correlates well with postoperative clinical success. Controlled clinical trials are needed to determine the value of multiple regression analysis in exotropia surgery. Discriminant analysis may represent an alternative statistical technique with application to this particular problem.

Humans↗

Penetrating keratoplasty in Lesotho.

Sixty-four Basotho patients underwent therapeutic penetrating keratoplasty in Lesotho, a developing African nation. The overall long-term success rate of 60.7% was comparable to similar series in developed countries. Analysis of variables found to significantly affect graft outcome included size of graft, anterior segment pathology, postoperative iris adhesion to graft wound, and onset of graft rejection during hospitalization or after discharge. McCarey-Kaufman medium was found to be highly successful for corneal storage up to seven days, and corneal transplantation across racial lines was not associated with increased immune rejection reactions.

Adolescent↗

Corneal transplantation following prolonged storage in M-K medium.

A successful penetrating keratoplasty was performed on a 25-year-old keratoconus patient inadvertently using a 79-year-old donor cornea which had been stored for 32 days at 4 degrees C in M-K medium. A thin, clear graft ten months postoperatively suggested either recovery of the original donor endothelium or possible host endothelial cell migration. The clinical advantages of prolonged M-K storage beyond seven days versus the increased risks of endothelial decompensation and secondary infection are reviewed.

Adult↗

Effect of phosphonoacetic acid in the treatment of experimental herpes simplex keratitis.

In the rabbit 5% phosphonoacetic acid ointment suppressed herpetic keratitis as well as 0-5% idoxuridine ointment. After 5 days of treatment quantitative virus titres showed that phosphonoacetic acid was superior to idoxuridine in the inhibition of herpes virus replication. Phosphonoacetic acid was found to be nontoxic to the eye in both clinical and histopathological studies. Recent reports suggest that the mechanism of action of phosphonoacetic acid appears to be the blocking of the virus DNA polymerase, which is essential for the synthesis of herpes virus DNA.

Animals↗

Irreversible inhibition of herpes simplex virus replication in BSC-1 cells by zinc ions.

Zinc sulfate added to the medium of herpes simplex virus-infected BSC-1 cells, at a concentration of 0.1 mM, inhibited the synthesis of infectious virus progeny by 95 to 96%. A concentration of 0.2 mM zinc sulfate inhibited herpes simplex virus synthesis by 99.8% as determined by centrifugation in sucrose gradients and by plaque assay on BSC-1 monolayers. The inhibition of herpes simplex virus replication in BSC-1 cells was found to be irreversible.

Cell Line↗

Penetrating keratoplasty in children.

Sixteen penetrating keratoplasties were performed in 14 patients less than 16 years old. Clear corneas were obtained in 62.5% of eyes with significantly improved vision in 56.2% of cases. The problems of postoperative treatments, complications, and amblyopia were found to be manageable. The visual benefits of corneal transplantation in selected cases in children appear to outweigh the difficulties and problems engendered by this procedure.

Adolescent↗