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Biomedical subjects

D Pavan-Langston

Publications and source records attributed to D Pavan-Langston.

At least 55 records · Page 3Linked to original sources

Efficacy of (E)-5-(2-bromovinyl)-2'-deoxyuridine in the treatment of experimental herpes simplex virus encephalitis in mice.

Systemic treatment of mice with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) showed a significant therapeutic efficacy against herpes simplex type 1 virus (HSV-1) encephalitis. With treatment initiated 12 h after viral inoculation and continued for 10 consecutive days, BVDU administered intraperitoneally in daily doses of 100-500 mg/kg increased the 21-day survival rates from 30 to 100% and reduced brain virus titers by 3-4 log10 on day 6 post-infection. Furthermore, at doses of 300-500 mg/kg per day BVDU prevented the establishment of latent virus infection in the trigeminal ganglia following intracerebral HSV-1 inoculation.

Animals↗

Superinfections in herpes simplex keratitis.

We reviewed 15 cases of culture-proven corneal superinfections in 15 patients (eight men and seven women ranging in age from 41 to 86 years) with recurrent herpes simplex keratitis. The factors that appeared to increase the risk of superinfection were the presence of an epithelial defect (found in all 15 cases), a history of recurrent herpetic keratouveitis (found in ten cases), and the use of topical corticosteroids (found in 13 cases). Eight of the 15 patients were taking antibiotics at the time the superinfections were diagnosed, indicating that topical antibiotics do not provide sufficient protection. Gram-negative rods were found in six cases (Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella oxytoca, Enterobacter cloacae, and Achromobacter sp.). Gram-positive organisms, often in association with another infecting agent, were found in six cases (Staphylococcus epidermidis, three cases; S. aureus, two cases; and Streptococcus sp., two cases). Fungal superinfections were found in three cases (Cephalosporium acremonium, Candida albicans, and Aspergillus fumigatus, one case each). Mycobacterium cheloni was found in two cases.

Administration, Topical↗

Ocular viral infections.

The most important viral organisms involving the eye are the DNA viruses herpes simplex, varicella-zoster, cytomegalovirus, adenovirus, and vaccinia virus. All of these agents except CMV may cause acute epithelial infection, sterile trophic ulceration due to basement membrane damage, deep corneal stromal immune reaction, and iritis. Although there are three excellent antiviral drugs commercially available, only HSV and vaccinia virus are highly sensitive to therapy with these antimetabolites; varicella-zoster virus and CMV are equivocally responsive and adenovirus has not been shown to be susceptible to these agents. In selected situations, topical or systemic corticosteroids are useful for managing any associated immune reactions in the eyes, but patients on these drugs should be monitored carefully both for superinfections and for interference with tissue healing that might ultimately threaten the integrity of the globe.

Adenoviridae Infections↗

Effect of acyclovir, bromovinyldeoxyuridine, vidarabine, and L-lysine on latent ganglionic herpes simplex virus in vitro.

Vidarabine and L-lysine did not prevent the in vitro reactivation of latent herpes simplex virus or block the further multiplication of reactivated latent virus. Acyclovir and bromovinyldeoxyuridine both blocked the reaction and the multiplication of reactivated latent virus, and transiently suppressed but did not eliminate latent virus from the sensory ganglia.

Acyclovir↗

Acyclovir and vidarabine for the treatment of herpes simplex keratitis.

Seventy-three patients were studied in a prospective, randomized double-controlled trial to determine the efficacy and side effects of 3 percent acyclovir or 3 percent vidarabine ointment in treating epithelial herpetic keratitis. Thirty-eight patients were treated with vidarabine and 35 patients with acyclovir. Sixty-eight patients ahd dendritic keratitis and five patients had geographic keratitis. There was no statistically significant difference between acyclovir and vidarabine for the treatment of epithelial keratitis in reference to epithelial healing, post-treatment visual acuity, or iritis. Neither drug was more effective in preventing secondary superficial stromal changes, nor was there any difference in the adverse reactions seen with acyclovir or vidarabine.

Acyclovir↗

Development of oral HSV-1 infection model in mice. Evaluation of efficacy of 5'-amino-5-iodo-2',5'-dideoxyuridine.

We developed a new model of oral HSV-1 infection in mice. After oral inoculation, 100 percent of mice developed the clinical lesions at the inoculated area and latent HVS infection in their trigeminal ganglia without mortality. The antiherpetic efficacy of AIdUrd, an agent specifically activated by herpesvirus-encoded enzyme, has been evaluated in this animal model. Early topical or systemic treatment of AIdUrd notably reduced the development of clinical lesions and the virus content in the inoculated lips. However, the establishment of latent HSV infection in the sensory ganglia was not influenced by AIdUrd treatment.

Animals↗

Chemotherapeutic efficacy of E-5-(2-bromovinyl)-2'deoxyuridine for orofacial infection with herpes simplex virus type 1 in mice.

Systemic or topical treatment with E-5-(2-bromovinyl)2'-deoxyuridine (BVDU) showed significant efficacy against orofacial infection with herpes simplex virus type 1 (HSV-1) in hairless mice. The chemotherapeutic response to BVDU was dose-dependent and clearly evident even when the treatment was initiated during the clinical manifestation of HSV-1 infection at 72 hr after inoculation. Early initiation of therapy with BVDU at 3 or 24 hr after inoculation significantly prevented the establishment of latent HSV infection in the trigeminal ganglia of mice, but systemic treatment with BVDU did not influence already established latent HSV-1. The chemotherapeutic efficacy of BVDU was comparable to that of acyclovir in the present animal model.

Acyclovir↗

Herpes Simplex keratitis: epidemiologic aspects.

Review of medical records of 141 patients with acute epithelial herpes simplex keratitis (HSK) showed that recurrences, but not initial episodes, were more likely to happen from November through February than during other months of the year (P less than .04). Other findings included a high male to female ratio in patients older than 40 years of age (1.67:1.0; P less than .03) and a median time interval between episodes (in patients with recurrent disease) of 1.5 years. Although we identified no risk factors for frequent recurrences or for severe disease, our data support the hypothesis that nonherpetic viral respiratory infections may trigger recurrences of HSK.

Adolescent↗

Ganglionic herpes simplex and systemic acyclovir.

The therapeutic and systemic effects of acyclovir on ganglionic herpes simplex virus (HSV) in mice were studied by varying the duration of treatment and the time of removal of ganglia for co-cultivation after treatment had ended. When treatment was started three hours after infection, it had a significant therapeutic effect even when the ganglionic culture was delayed 17 days after the end of acyclovir therapy. When treatment was started 24 hours after infection, it had no significant effect under the same circumstances. The treatment of established latent ganglionic HSV for 15 days with acyclovir had a significant therapeutic effect compared with control mice when ganglia were cultured two days after treatment had ended, but this effect was lost by ten and 21 days after the end of therapy. This indicates that acyclovir has a transient suppressive effect on part of the viral ganglionic reservoir, but it also indicates that these titers quickly reestablish themselves with the removal of drug therapy.

Acyclovir↗

Ac2IDU, BVDU, and thymine arabinoside therapy in experimental herpes keratitis.

The therapeutic efficacy of three new antiviral agents-5-iodo-3',5'-diacetyl-2'-deoxyuridine (diacetylidoxuridine, 1% Ac2IDU), E-5-(2-bromovinyl)-2'-deoxyuridine (0.25% BVDU), and 3% thymine arabinoside-is compared with available antivirals in an experimental model of herpes simplex virus type 1 (HSV-1) keratitis in New Zealand white rabbits. Compared with placebo, Ac2IDU significantly reduced ulcerative keratitis on days 4 through 8 after inoculation with virus and iritis on day 8 after inoculation. Compared with placebo, thymine arabinoside reduced ulcerative keratitis but not significantly. Thymine arabinoside caused significant iritis in all eyes. The epithelial disease in BVDU-treated eyes was significantly less than that in placebo-treated eyes on days 5 through 8 after inoculation. The results indicate that 1% Ac2IDU and 0.25% BVDU were effective in our ocular model of HSV-1 keratitis, whereas thymine arabinoside was not.

Animals↗

Acyclovir and vidarabine in the treatment of ulcerative herpes simplex keratitis.

In a masked controlled study, we treated 41 patients who had active herpes simplex corneal ulcers with either 3% acyclovir of 3% vidarabine ointment five times daily for 14 days. There was no statistically significant difference between the two drugs with reference to mean healing time, efficacy of healing, development of stromal keratitis or iritis, post-treatment visual acuity, or adverse reaction.

Acyclovir↗

Treatment of experimental herpetic interstitial keratitis with medroxyprogesterone.

A model of herpes simplex interstitial keratitis was developed in rabbits sensitized with live herpes simplex virus (HSV) type 2 and challenged intrastromally with live virus. This model was used to evaluate the effects of subconjunctival medroxyprogesterone acetate on the course of the disease and on collagenase levels in the treated corneas. Whether treated prophylactically or therapeutically, the medroxyprogesterone-treated groups had substantially less stromal infiltration and neovascularization than the controls. The clinical effects corresponded with a marked reduction in the polymorphonuclear leukocyte infiltrate histologically, and the suppression of latent and active collagenase activity in the treated corneas cultured in vitro. However, epithelial disease was exacerbated in prophylactically treated animals. Medroxyprogesterone appears to be useful in the treatment of herpetic interstitial keratitis as an anti-inflammatory agent as well as an inhibitor of collagenase production but, like the corticosteroids, it can exacerbate epithelial disease.

Animals↗

Collagenase levels in a new model of experimental herpetic interstitial keratitis.

A reproducible model of severe herpetic interstitial keratitis was developed by injecting live herpes simplex virus type 2 intrastromally into the corneas of presensitized rabbits. Herpes-infected corneas showed significantly more stromal infiltration and vascularization, iritis, conjunctivitis, and epithelial disease than the control corneas injected with cell supernatant without virus. Levels of total collagenase detected in the culture media of the herpes-infected corneas were high and were similar to those observed previously in alkali-burned rabbit corneas. Unlike alkali-burned corneas, the herpes-infected corneas showed much more of the enzyme in the latent form during the first two days of culture.

Animals↗

Topical therapeutic efficacy of 9-(2-hydroxyethoxymethyl)guanine and 5-iodo-5'-amino-2',5'-dideoxyuridine on oral infection with herpes simplex virus in mice.

The therapeutic efficacy of two new antiviral agents, 5-iodo-5'-amino-2', 5'-dideoxyuridine (AIdUrd) and 9-(2-hydroxyethoxymethyl)guanine (ACV), in the model of mouse lip inoculated with herpes simplex virus type 2 is reported. The effects on development of clinical lesions, viral replication in the inoculated lips, and establishment of latent viral infection in the trigeminal ganglia were observed. The earlier the treatment with AIdUrd and ACV was initiated after inoculation, the better was the chemotherapeutic effect. AIdUrd and ACV treatment, when initiated 48 and 72 hr after inoculation, respectively, showed no chemotherapeutic efficacy. Establishment of viral latent infection in sensory ganglia was significantly prevented only when ACV treatment was initiated very early (1 or 3 hr) after inoculation. The results indicate that both drugs have significant antiviral activity, in part dependent on the time of initiation of therapy, and that ACV is superior to AIdUrd as a topical agent for therapy of herpes simplex virus type 2 infections.

Acyclovir↗