The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and differential diagnosis for classifying microscopic lesions observed in the male reproductive system of laboratory rats and mice, with color microphotographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available for society members electronically on the Internet (http://goreni.org). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for lesions of the male reproductive system in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.
This retrospective study was performed to determine the range, occurrence and incidence of spontaneously arising histopathological findings of the cardiovascular system in purpose-bred laboratory nonhuman primates. Data were collected from 84 controlled toxicological studies with equal numbers of male and female animals and full tissue lists. Attempts were also made to standardize pathological terms used by various original pathologists. Tissue sections from 2464 animals, which included 2050 cynomolgus monkeys (Macaca fascicularis), 284 common marmosets (Callithrix jacchus) and 130 rhesus monkeys (Macaca mulatta) were examined. The most common cardiac finding was focal myocardial inflammation, subcategorized as either "inflammatory cell infiltration" (339) or "focal myocarditis" (131). Other cardiac findings included mineralization (29), endocarditis (16), pericarditis (10), squamous cysts (6) and ectopic thyroid tissue (5). Perivasculitis/vasculitis in the kidney, lung, meninges, sciatic nerve, and other tissues (206) was the most common vascular lesion. Focal myocarditis was more common in male (60%) than female (40%) animals. Cardiac mineralization and extramedullary hematopoiesis were more common in marmosets than other species while ectopic thyroid tissue was present in marmosets and cynomolgus monkeys. To our knowledge, this is the first study to demonstrate the range and incidence of spontaneous cardiovascular lesions in laboratory nonhuman primates.Keywords. Cardiovascular; spontaneous pathology; nonhuman primate; cynomolgus; rhesus; marmoset. INTRODUCTIONIn preclinical toxicology studies, drug-induced cardiovascular lesions continue to be an important area of concern, in particular with respect to assessment of cardiovascular safety of drugs intended for human use. In the course of such studies, it is not uncommon to encounter drug-induced histopathological lesions in the heart and blood vessels that are similar to those that may arise spontaneously in control animals. Since this can considerably hinder the evaluation of toxicological compounds, it is important for pathologists to be able to recognize such background changes in control animals of a test species. Although nonhuman primates are widely used in preclinical toxicology studies due to their phylogenic relationship to humans, specific information on the range of background findings is not readily available. This review was conducted in order to report and characterize the range and incidence of spontaneous background microscopic cardiovascular lesions in young, healthy cynomolgus monkeys (Macaca fascicularis), rhesus monkeys (Macaca mulatta) and common marmosets (Callithrix jacchus) purposebred for laboratory use.
Haemobartonella felis infection was demonstrated in 38 cats which could be divided into four groups as follows: group A, feline leukaemia virus (FeLV) free cats with H felis infection alone; group B, FeLV free cats with H felis infection and other clinical conditions; group C, FeLV positive cats with H felis infection but no clinical manifestation of FeLV related or any other intercurrent disease; and group D, FeLV positive cats with H felis infection and clinical manifestations of FeLV related or other diseases. Cats in group A were healthy carriers of the infection and none was anaemic, whereas some in group B had clinical haemobartonellosis and anaemia. This anaemia was mainly mild, normocytic and normochromic. Most of the cats in group C and all in group D were more severely ill and anaemic, the anaemia usually being macrocytic and hypochromic. Splenomegaly occurred only in groups C and D. Treatment with tetracyclines did not eliminate H felis from any of the cats and blood transfusions were ineffective in promoting long term recovery from anaemia in cats with intercurrent H felis and FeLV infections. The findings in the cats in groups C and D were further compared with those in a fifth group of cats which were infected with FeLV but free of H felis.
A survey of the incidence of feline leukaemia virus (FeLV) infection in cats in a large urban area was made by studying the prevalence of antibodies to feline leukaemia virus-associated cell membrane antigens. Two serological tests were used, immunofluorescence and a mixed immunoglobulin rosette technique. The overall incidence of cats with antibodies was 40%, contrasting with 6% in the surrounding rural area. Only 6% of urban kittens were positive while 50% of adults had antibodies. The incidence in adults rose from 29% at 5-6 months to 74% in cats over 3 years. Stray cats had an incidence twice as high as that of domestic pets. These results support and extend earlier findings that FeLV infection is common and is horizontally transmitted.
A neoplastic mass compressing the left cerebellar hemisphere and hindbrain was observed at trimming in a 3½-year-old male cynomolgus monkey from a control dose group. Microscopically, the neoplastic mass was nonencapsulated, invasive, and showed two morphological patterns. The predominant area consisted of densely packed undifferentiated, polygonal to spindle cells arranged in vague sheets supported by a scant fibrovascular stroma. The other area was less cellular and composed of round neoplastic cells separated by eosinophilic fibrillar material. Immunohistochemical staining for vimentin, synaptophysin, glial fibrillary acidic protein, neuron-specific enolase, neurofilament, and S-100 confirmed the presence of primitive undifferentiated neuroectodermal cells and some cells with neuronal or glial differentiation. On the basis of histopathology and immunohistochemical findings, a diagnosis of cerebellar primitive neuroectodermal tumor with neuronal and glial differentiation was made. Primitive neuroectodermal tumors are rare in animals including nonhuman primates; this is the first published report in this species.
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