M. Nixon Ellis

Progressive mucocutaneous herpes simplex infection due to acyclovir-resistant virus in an immunocompromised patient: Correlation of viral susceptibilities and plasma levels with response to therapy

Rapidly progressive disease due to acyclovir-resistant herpes simplex has not been described. We report such a case and detail successful patient management using viral sensitivities and plasma acyclovir levels to guide therapy. Response was correlated with plasma levels above those inhibiting viral growth by 50% (ID50) in vitro.

Feline immunodeficiency virus infection of cats as a model to test the effect of certain in vitro selection pressures on the infectivity and virulence of resultant lentivirus variants

Three groups of specific pathogen-free (SPF) domestic cats, each containing 5 animals, were infected with one of three closely related FIV variants and monitored for 36 weeks. A fourth group of 5 cats was sham-infected and served as uninfected controls. FIV variants included: (1) a fully virulent animal passaged FIV-Petaluma; (2) a Crandell feline kidney (CrFK) cell-adapted FIV-Petaluma (FIV-CrFK); and (3) a variant of FIV-CrFK (FIV-CrFKAZT) that had been selected in vitro for resistance to azidothymidine. Cats infected with fully virulent FIV-Petaluma strongly seroconverted, became persistently viremic, and exhibited lymphadenopathy, neutropenia, and inversion of the CD4+:CD8+ T cell ratio. Cats infected with FIV-CrFK seroconverted but the antibody responses were much weaker and more variable; two of the cats became transiently viremic and no hematologic abnormalities or clinical signs of illness other than a very mild lymphadenopathy were observed. None of the five cats inoculated with FIV-CrFKAZT seroconverted, became viremic, or exhibited any gross or hematologic signs of disease, even though proviral DNA was transiently detected in tissue following inoculation. This study demonstrates that the FIV infection model can be used to assess differences in the virulence of FIV variants, including variants selected for antiretroviral drug resistance.

The effect of nicotinamide on microvascular density and thermal injury in rats

The effects of nicotinamide on the microvasculature and wound healing were examined in rats subjected to thermal injury. Rats (250 g) were treated with 50 mg nicotinamide intraperitoneally twice daily for 21 days and then heart and brain biopsies were taken. Skin biopsies were removed from sites in and adjacent to the injury throughout the course of healing. Tissues were stained for alkaline phosphatase and capillary length density was determined by morphometric analysis. Significant increases were observed in the heart, brain, and dermal tissue of treated animals compared to controls. Capillary density in the injured skin was significantly greater when compared to the injured skin of saline-treated controls. The injuries of the rats that were treated systemically with nicotinamide healed significantly faster than saline-treated as determined by planimetric evaluation of the granulation bed and eschar.

6-Dimethylamino-9-(β-D-arabinofuranosyl)-9H-purine : pharmacokinetics and antiviral activity in simian varicella virus-infected monkeys

6-Dimethylamino-9-(beta-D-arabinofuranosyl)-9H-purine (ara-DMAP) effectively prevented the development of rash and appreciably reduced viremia in simian varicella virus-infected monkeys. Doses of 100 and 50 mg/kg/day, administered orally, were highly effective. The lowest dose of 20 mg/kg/day was much less effective in preventing moderate viremia. However, the 20 mg/kg/day did prevent the development of rash in two of three monkeys. All three doses of ara-DMAP reduced liver infection as reflected by lower aspartate aminotransferase values in the sera of the African green monkeys. Orally administered ara-DMAP was rapidly absorbed. However, significant variation among individual monkeys in the AUC values, peak plasma levels, and plasma half-lives were observed.