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Biomedical subjects

E D Varnell

Publications and source records attributed to E D Varnell.

At least 37 records · Page 2Linked to original sources

K-Sol corneal preservation at room temperature.

K-Sol, a recently developed corneal storage medium that contains purified chondroitin sulphate in tissue culture medium (TC 199), is capable of preserving corneal tissue for 14 days at 4 degrees C. To study the effect of tissue storage in K-Sol at room temperature we preserved rabbit corneas in K-Sol and M-K medium for three or seven days at 25 degrees C. All of the corneal endothelial sheets were intact after three days. At seven days the change in pH of the K-Sol medium was less than that of M-K medium. Corneas preserved in M-K medium showed swelling of mitochondria and a decrease in the number of cytoplasmic organelles. Corneas preserved in K-Sol had organised cytoplasmic organelles and nuclei. Scanning electron micrographs revealed well preserved endothelial sheets. Corneas stored in the two media showed no significant difference in thickness. A pair of human corneas preserved in K-Sol at room temperature for six days maintained about 95% of the endothelial sheet in good condition. Small separations were observed between some of the endothelial cells. However, even in these areas, the cytoplasmic organelles were well preserved. It appeared that K-Sol is more stable than M-K medium at room temperature, and that both rabbit and human corneas can be preserved in good condition in K-Sol for at least six days at 25 degrees C.

Animals↗

Histological study of corneas preserved in two new media.

A new corneal preserving medium (K-Sol), developed by Kaufman and others, contains purified chondroitin sulphate, TC 199, HEPES buffer, and gentamicin. Another new medium (JM) containing bicarbonate-free glucose-phosphate Ringer solution and dextran 70 has been developed in Japan. New Zealand white rabbit corneas with scleral rims were stored in each medium at 4 degrees C for one or two weeks. The condition of the endothelium was evaluated histologically. Corneas preserved in both media were in good condition at the end of one week. Corneas preserved in K-Sol for two weeks showed fewer endothelial changes than similar tissue stored in JM for two weeks. Corneal swelling was also less in corneas preserved in K-Sol, than in corneas preserved in JM.

Animals↗

A primate model for acute and recurrent herpetic keratitis.

Twelve squirrel monkeys were inoculated in both eyes with the Rodanus strain of herpes simplex virus type 1 (HSV-1) and were examined for the presence of acute epithelial keratitis. All of the eyes developed dendritic keratitis within 72 hours after inoculation. The twelve monkeys plus two additional similarly infected monkeys were also examined for the presence of clinical recurrences of ocular herpes infections and spontaneous shedding of virus in their tears. Two of the eyes developed stromal disease, and 13 of the monkeys had at least one episode of recurrent clinical epithelial disease. Virus was isolated from two of the eyes with recurrent dendrites.

Animals↗

K-Sol corneal preservation.

K-Sol, a new cornea preserving solution which contains no calf serum of foreign protein and is used for refrigerated storage of donor tissue, has storage procedures identical to those currently used for tissue preservation in McCarey-Kaufman medium. K-Sol can keep corneas alive and usable for penetrating keratoplasty for at least two weeks. The clinical results in a series of 17 patients indicated that tissue preserved in K-Sol for as long as two weeks, even when used by inexperienced surgeons in difficult or unfavorable cases requiring extensive anterior segment reconstruction, including reoperations or retained intraocular lenses, gave results virtually identical to those obtained with tissue preserved in McCarey-Kaufman medium for only two or three days.

Adult↗

Effect of the herpes simplex virus genome on the response of infection to corticosteroids.

The type and severity of ocular herpetic disease, as well as the pattern of recurrence, have been shown to be determined by the virus genome. We infected rabbit eyes with two closely related recombinant strains of herpes simplex virus type 1 and treated one half of the eyes in each group with corticosteroids before or immediately after virus inoculation. The severity of disease in the first week was similar in the treated and untreated eyes infected with the F(MP)F strain; however, with F(MP)E infection, the disease in the treated eyes was significantly worse than the disease in the untreated eyes. Cultures of corneal virus showed similar titers in all of the groups, but cultures of trigeminal ganglia indicated that increased severity of disease did not result in an increased tendency toward ganglionic colonization. The results suggest that the response to corticosteroids is another factor that is determined by the genetics of the infecting virus, but that there is no correlation between worsening of disease with corticosteroid treatment and the establishment of virus latency.

Adrenal Cortex Hormones↗

Acyclovir in the treatment of herpetic stromal disease.

Seventeen patients (ten women and seven men, 23 to 72 years old) with stromal herpetic disease were treated with topical and oral acyclovir for 14 days. Of the 12 patients with disciform edema, five showed minimal improvement, four showed no change, and three showed worsening of their disease. Of the five patients with necrotizing stromal keratitis, one improved, one showed no change, and three became worse. The patients who had been treated with corticosteroids previously had a statistically significantly worse outcome than those who had not been so treated. One patient with necrotizing stromal keratitis showed virus particles in tissue specimens obtained by superficial lamellar keratectomy. Thus, acyclovir was not effective in the treatment of disciform edema or necrotizing stromal keratitis. Further studies are needed to ascertain whether the drug is therapeutically ineffective or whether acyclovir did not reach the stroma in amounts sufficient to affect the course of stromal disease in the human eye.

Acyclovir↗

Virus chemotherapy: antiviral drugs and interferon.

Early antiviral drugs, such as idoxuridine and vidarabine, are less effective than newer drugs, such as trifluorothymidine and acyclovir. However, trifluorothymidine is less subject to the development of drug-resistant strains and can be administered topically as a clear drop, which increases patient compliance. Acyclovir has low toxicity and is selective for virus-infected cells because it must be phosphorylated by the viral thymidine kinase to become active. However, drug-resistant strains are produced relatively easily in vitro and may also develop in man with long-term use. To date, no antiviral drug alone has been shown to be effective in the treatment of stromal disease, and no antiviral drug is able to eradicate virus latent in the ganglia and thereby prevent recurrent herpetic infections. Combinations of antiviral drugs and antiviral drugs and interferon are being tested for enhanced efficacy in the treatment of ocular herpetic disease, and for prophylactic effects. The development of recombinant interferons has reduced cost and increased availability, but the effects of the 'manufactured' interferon are not identical to those of natural human leukocyte interferon in all experimental situations.

Acyclovir↗

The lack of effect of tunicamycin and 2-deoxy-D-glucose on corneal stromal herpes in rabbits.

A rabbit model for herpes simplex virus (HSV) stromal keratitis, produced by intrastromal injection of live virus, was used to evaluate the effects of tunicamycin and 2-deoxy-D-glucose therapy. In vivo and in vitro evidence suggests that HSV strains that produce stromal disease secrete relatively large amounts of highly antigenic glycoproteins. Also, various studies have shown that tunicamycin and 2-deoxy-D-glucose inhibit the production of complete HSV-specific glycoproteins. Thus, these drugs might be capable of mitigating the clinical manifestations of HSV stromal keratitis by reducing the antigenic load. However, when topical therapy with tunicamycin and/or 2-deoxy-D-glucose was begun in rabbit eyes, the day after intrastromal inoculation of live RE strain HSV and several days before the appearance of stromal disease, no difference in the clinical course of herpetic ocular disease was seen between the experimental (treated) and control (untreated) groups.

Animals↗

Differences in natural and recombinant interferon for herpes keratitis in two animal models.

Natural human leukocyte interferon (natural HuIFN-alpha) and recombinant leukocyte A interferon (recombinant A HuIFN-alpha) were tested for prophylactic and/or therapeutic effects in reducing the severity of keratitis in rabbit and monkey eyes infected with McKrae strain herpesvirus. The results showed that the two interferons acted differently in the rabbit eye; combined prophylactic and therapeutic administration of natural interferon mitigated the disease, while recombinant interferon had no effect. In monkeys, the two interferons acted similarly. Combined prophylactic and therapeutic administration reduced disease findings, while therapeutic administration alone had no effect. Thus, studies in rabbits are not accurate predictors of primate study results; whether or not nonhuman primate results can be extrapolated to humans remains to be seen.

Animals↗

Herpes simplex keratitis.

Avirulent strains of herpes simplex type 1 (HSV-1) infect and shed and colonize the ganglia in rabbits. This primary infection reduces the severity of subsequent infection by virulent virus and prevents ganglionic colonization by even very virulent neurotropic virus. Only a small proportion of the human population known to be infected with HSV-1 develops clinical disease. It is possible that the severity and likelihood of recurrence of this disease is determined by the virulence of the original infecting HSV-1 strain. In addition, there is evidence for differences in antigenicity among the various virus strains, and it may be that the development of stromal disease is related to the host response to these differences. Among the drugs generally available for the treatment of herpetic disease, trifluridine is currently the newest and most effective. Other compounds, such as acyclovir and BVDU, are being developed; because these drugs are specific for the virus and do not interfere with the metabolic processes of normal cells, they have a very low toxicity. Also, it may be that these compounds have a combined effect with other antiviral agents, such as vidarabine, increasing their potency against stromal disease and iritis.

Animals↗

Oral antiviral drugs in experimental herpes simplex keratitis.

Chronic oral administration of acyclovir or bromovinyl deoxyuridine to rabbits did not prevent recurrence of virus shedding or clinical corneal disease, nor did it alter the clinical course of recurrences of ocular herpetic disease or result in the appearance of resistant virus in tears.

Acyclovir↗

Initial herpes simplex virus type 1 infection prevents ganglionic superinfection by other strains.

The ganglia of rabbits infected with a relatively benign strain of herpesvirus (E-43) and challenged with either of two virulent neurotrophic strains (MP or McKrae) were found to be colonized only by the initial benign infecting strain. Primary infection with the E-43 strain resulted in milder disease when the animals were infected with MP or McKrae strains and also prevented colonization of the ganglion by these strains. Neutralization with anti-glycoprotein C, plaque morphology, cytopathic effects, reconstruction experiments, and restriction endonuclease analysis indicated that the virus recovered from the ganglion was the initial infecting E-43 strain; no traces of the challenging MP and McKrae strains were found. The challenging McKrae strain was shed for several weeks in a few animals, but the virus isolated from the trigeminal ganglia of these animals was the primary infecting E-43 strain. These results suggest that initial infection with a relatively benign strain of herpesvirus may prevent superinfection of the ganglion (but not necessarily the end organ) by highly virulent herpes simplex virus strains and could have significant implications in the consideration of immunization against this disease in humans.

Animals↗

Effect of PMMA and silicone lens materials on normal rabbit corneal endothelium: an in vitro study.

Various silicone elastomer intraocular lens materials were compared to PMMA intraocular lens material to ascertain the relative degree of damage caused by each to the rabbit corneal endothelium in vitro. The soft elastomer materials which had been surface treated by electrical molecular rearrangement appeared to cause the least damage and would therefore possibly be most successful for intraocular lens manufacture.

Animals↗

Toxicity and tolerance of 9-(2-hydroxyethoxymethyl)guanine.

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is a new antiviral agent which has specific activity in virus-infected cells. The drug has a high therapeutic index in animal and laboratory models but had not been tested for toxicity in human eyes at the time of this study. A randomized double-blind study on patients requiring antiviral therapy for treatment or prophylaxis of herpetic ocular infections revealed minimal irritation associated with topical administration. Further controlled studies will be necessary to evaluate this compound's clinical efficacy.

Acyclovir↗

Effect of 9-(2-hydroxyethoxymethyl)guanine on herpesvirus-induced keratitis and iritis in rabbits.

Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular functions. The recently reported 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) is selectively phosphorylated by viral thymidine kinase but not by normal cellular thymidine kinase. Our present studies show that the acycloguanosine is as effective in treating herpetic keratitis in the rabbit as iododeoxyuridine and trifluorothymidine when given topically as an ointment. It is also effective when given intravenously for the treatment of herpetic iritis and is effective in preventing death from encephalitis in rabbits.

Animals↗

Lack of levamisole effect on experimental herpes keratitis.

Levamisole, which is an anthelminthic, can restore depressed cell-mediated immunity (CMI) under some circumstances. In a controlled trial of experimental herpetic keratis in rabbits, levamisole was found to have no significant effect on acute herpetic keratitis or its recurrence rate. This is consistent with previous findings that other nonspecific CMI stimulation had no effect on recurrences of experimental herpes keratitis. Because of the known tendency of levamisole to produce agranulocytosis, we believe it should not be used in man unless proven effective in a carefully controlled double-blind study.

Animals↗