Genomic variability among globally distributed isolates of equine arteritis virus.

Equine arteritis virus (EAV), a non-arthropod borne togavirus, has been shown to have a global distribution. To date, no major antigenic variation has been demonstrated between EAV isolates from different geographic origins. In this study, the genomic RNA of EAV isolates obtained from horses of different breeds in various countries around the world was oligonucleotide fingerprinted. Comparisons of these fingerprints were used to determine the extent of genomic variation among such isolates. Comparisons among isolates from North American horses revealed, for the most part, oligonucleotide homologies of less than 60%. Only 29 of the 98 comparisons revealed greater than 60% oligonucleotide homology. Nonetheless, several comparisons indicated a close epidemiologic relationship between isolates from horses of different breeds located in different states. Though all European isolates were of Standardbred origin and were from horses located in northern European countries, the majority had oligonucleotide homologies of less than 60%. Where oligonucleotide homology was apparent, it was, with one exception, greater than 70%. The two isolates from New Zealand had 93.2% oligonucleotide homology. This is indicative of an extremely close epidemiologic relationship. Comparisons between EAV isolates from around the world revealed oligonucleotide homologies between viruses from North America, Europe and New Zealand. In several instances, this homology was greater than 70% and in one case greater than 80%. No oligonucleotide homology was evident in comparisons involving the virus from South Africa. The high level of genomic conservation between certain EAV isolates of disparate geographic origins may reflect dissemination of the virus associated with the international movement of horses. The extent of genomic variation demonstrated between most of the EAV isolates used in this study confirms the need for further investigation of genomic heterogeneity among strains of this virus before techniques that rely upon nucleic acid hybridization can be effectively applied as diagnostic procedures.     

Toxic peripheral neuropathy with demyelination in Sprague-Dawley rats given CGS 21595--a 5-lipoxygenase inhibitor.

Male and female Sprague-Dawley rats were given CGS 21595, a pro-drug that is almost immediately metabolized to CGS 19213, a naphthoquinone that acts as a 5-lipoxygenase inhibitor. The compound was administered by gavage to five groups of Sprague-Dawley rats (group Nos. 1, 5, n = 30; group Nos. 2-4, n = 20) at daily doses of 0, 50, 150, 500, or 1,000 mg/kg for 13 weeks. Rats in the higher dose groups had a reduced weight gain, but significant neurologic signs were not observed. A peripheral neuropathy consisting predominantly of myelin destruction in the spinal nerve roots and sciatic nerves in male rats treated with greater than or equal to 150 mg/kg CGS 21595 and in female rats treated with greater than or equal to 50 mg/kg CGS 21595 for 13 weeks. This lesion was not fully reversible after a recovery period of 4 weeks. Lesions consisted of ballooning of myelin sheaths, infiltration by macrophages, demyelination, and occasional areas of remyelination. Axons were generally preserved, and the brain and spinal cord were not affected. Male and female rats in all treatment groups had cytoplasmic hyaline droplets in the proximal renal tubules. This change was reversible after 4 weeks and was not associated with any other adverse effects on the kidney.     

Canine distal renal tubular acidosis and urolithiasis

Distal RTA is characterized by decreased distal renal tubular hydrogen ion secretion, decreased ability to acidify urine, hypercalciuria, hyperphosphaturia, hypocitraturia, and metabolic acidosis. Because of the resulting alterations in urine composition and pH, patients with distal RTA are predisposed to urolithiasis and renal calcification. Diagnosis of distal RTA is important because it is a potentially reversible disorder that, left untreated, may cause nephrocalcinosis, recurrent urolith formation, moderate to severe metabolic acidosis, and renal failure.     

0–7–21 Radiation Therapy for the Treatment of Canine Oral Melanoma

Eighteen dogs with malignant melanoma of the oral cavity were treated with high-dose per fraction (0–7–21) radiation therapy. Eight hundred cGy was administered on days 0, 7, and 21 for a total dose of 2,400 cGy in 3 weeks. Of 17 dogs evaluated, 9 (53%) had a complete remission and 5 (30%) achieved a partial remission with an overall response rate of 83%. Local failure occurred in 2 of the 9 dogs where a complete response was initially observed. One dog died of intercurrent disease, and one died of metastatic disease without evidence of local recurrence. Five dogs are alive and free of disease 9 to nineteen months from the initiation of therapy. The 0–7–21 protocol was well-tolerated, and acute radiation reactions were low-grade and limited to the skin. The results of this study demonstrate that oral melanomas in dogs are responsive to radiation. 0–7–21 radiation therapy offers a viable alternative to radical excision, especially when tumor volume or location would require cosmetically or functionally debilitating surgery.