Dermatosparaxis in two Limousin calves.

BACKGROUND: An unusual presentation of skin disease was identified in two related neonatal Pedigree Limousin calves presented to University Veterinary Hospital, University College Dublin, following detailed post mortem examination a diagnosis of dermatosparaxis was made. Dermatosparaxis in animals or Ehlers Danlos Syndrome, which is the analogous condition seen in humans, is a connective tissue disorder characterised by extreme skin fragility. To the authors' knowledge this is the first report of such a diagnosis in the Limousin breed and the features of this lethal phenotype were severe in comparison to previous reports of the condition. CASE PRESENTATION: Two calves, which were full siblings, a pedigree Limousin bull (Calf A) and pedigree Limousin heifer (Calf B) were examined clinically after presenting collapsed since birth, both had grossly abnormal skin with multiple skin fissures visible and both calves were subsequently euthanised. Both calves underwent gross post mortem examination, after which histological samples were reviewed and electron microscopical examination of selected skin samples was carried out. Histological features of dysplastic dermal collagen were identified. The diagnosis of dermatosparaxis in the Limousin breed was confirmed. Genetic testing was conducted to determine if the current cases had the same mutation as has previously been described in Belgian Blue cattle. Some common parentage was traced but genetic testing did not show a similar mutation to that previously described in cattle. The specific genetic cause in this case is unknown. CONCLUSIONS: This is the first report of dermatosparaxis in the Limousin and the presentation of the dermatosparaxis phenotype has some noteworthy features thus further genetic testing is required to pinpoint the causative mutation or other genetic defect. Given the popularity of the breed and the lethal nature of the phenotype in this case it is important to raise awareness of the condition.

Giant thoracic schwannoma in a rhesus macaque (Macaca mulatta).

A 15-y-old male rhesus macaque with a 3-d history of labored breathing, was culled from a nonhuman primate research colony after thoracic radiographs and exploratory surgery revealed a 10-cm, well-circumscribed space-occupying mass in the posterior thoracic cavity. The multilobulated cystic and necrotic neoplasm was composed of interlacing streams and fascicles of neoplastic spindle cells arranged in Antoni A, and less commonly, Antoni B patterns. Verocay bodies were present also. The neoplasm was encapsulated mostly, and histomorphologic features were benign. Immunohistochemistry indicated that neoplastic cells were positive for vimentin, S100, glial fibrillary acidic protein, and nerve growth factor receptor. Reticulin histochemical staining and immunohistochemical stains for collagen IV and laminin showed a prominent basal lamina surrounding the neoplastic cells. The histologic features and results of the immunohistochemical stains confirmed peripheral nerve origin and were consistent with schwannoma. To our knowledge, this is the first case of thoracic schwannoma in a rhesus macaque and the second reported case of schwannoma in a nonhuman primate.

Corynebacterial necrohemorrhagic cystitis in two female macaques.

We describe severe necrohemorrhagic cystitis in a female rhesus macaque and a female cynomolgus macaque due to colonization of the urinary bladder by Corynebacterium sp. Clinically, both macaques presented with perineal bleeding and depression and, despite extensive and prolonged treatment, succumbed to the disease. At necropsy, the contents of the urinary bladders in both cases were hemorrhagic to greenish black, and the bladder mucosa was necrotic. The major microscopic finding in each case was transmural necrohemorrhagic cystitis, with vasculitis, fibrin thrombi, and myriad gram-positive coryneform bacilli. Corynebacterium renale, Streptococcus acidominimus, and S. oralis were cultured from the urinary bladder of the rhesus macaque, and a nondiphtheritic Corynebacterium was cultured from the urinary bladder of the cynomolgus macaque. Neither animal had any other noteworthy pathologic lesions unrelated to bacterial cystitis. Corynebacterial necrohemorrhagic cystitis therefore was determined to be the cause of death in both animals. To our knowledge, this is the fi rst report of corynebacterial cystitis in nonhuman primates.

Pathologic findings associated with delayed death in nonhuman primates experimentally infected with Zaire Ebola virus.

Zaire Ebola virus infection in macaques causes a fatal disease with a pathogenesis similar to that in humans. During several independent therapy studies, we noted altered tissue tropism in 6 rhesus macaques that survived longer than those with a typical disease course. The mean time to death for these 6 macaques was 21.7 days, which is significantly longer than the average mean time to death of 8.3 days for 20 untreated historical control animals. In addition to living significantly longer, these 6 animals exhibited a variety of deteriorating clinical signs with pathologic findings that were not seen in the untreated control animals, as well as the presence of viral antigen in the brain, eye, pancreas, thyroid, and lung. We suggest that treatment extended the time course of the disease and permitted the virus to infect tissues not usually affected in the typical model.

Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever.

BACKGROUND: Infection of primates with Zaire ebolavirus (ZEBOV) leads to hypotension, coagulation disorders, and an impaired immune response and, in many ways, resembles severe sepsis. Rapid decreases in plasma levels of protein C are a prominent feature of severe sepsis and ZEBOV hemorrhagic fever (ZHF). Currently, recombinant human activated protein C (rhAPC [Xigris; Eli Lilly]) is licensed for treating human patients with severe sepsis who are at high risk of death. The aim of this study was to test the efficacy of rhAPC as a potential treatment for ZHF. METHODS: Fourteen rhesus macaques were challenged with a uniformly lethal dose of ZEBOV; 11 of these monkeys were treated by intravenous infusion with rhAPC beginning 30-60 min after challenge and continuing for 7 days. Three control monkeys received sterile saline in parallel. RESULTS: All 3 control monkeys died on day 8, whereas 2 of the 11 rhAPC-treated monkeys survived. The mean time to death for the rhAPC-treated monkeys that did not survive ZEBOV challenge was 12.6 days. The difference in survival was significant when the rhAPC-treated monkeys were compared with historical controls. CONCLUSIONS: The experimental findings provide evidence that ZHF and severe sepsis share underlying mechanisms and may respond to the same therapies.