Proliferative Optic Neuropathy in Horses.

An asymptomatic, ophthalmoscopically visible proliferation affected the optic disc and nerve of two aged horses. The lesion consisted of an accumulation of foamy cells, histologically akin to fat cells, which contained an unidentified lipid-like material. The affected area and its environs were permeated by tortuous, thickened blood vessels with heavy deposits of collagen in their walls. The neuropathy is considered to be a storage disease, and although the product stored is unidentified, the lesion is similar to that of human xanthelasma. The neuropathy seems distinct from the exudative optic neuritis of horses that has been known since 1890.

From Osler to Olafson. The evolution of veterinary pathology in North America.

Most branches of biological science in North America developed first in the United States, and later were taught and practiced in Canada. An exception was veterinary pathology, which as a discipline taught in veterinary colleges and as a field of research, developed first in Canada, and from there crossed the border to the United States. Pathology was first taught at the Montreal Veterinary College, founded in 1866 by Duncan McEachran, a graduate of the Edinburgh Veterinary College. From the outset, he formed a close association with the medical faculty of McGill University, permitting his students to attend the same classes in the basic subjects with the medical students. Eventually, the Montreal Veterinary College became formally affiliated with McGill University, as the Faculty of Comparative Medicine and Veterinary Science. The McGill veterinary faculty was forced to close for economic reasons in 1903, but it left an enduring legacy, particularly in the field of veterinary pathology. The legacy, a novel concept in the 1870's, was that pathology was the cornerstone of a veterinary education; the place where anatomy, physiology, chemistry and botany met with the clinical subjects, and gave the latter meaning. This tradition was formed at the Montreal Veterinary College by the world renowned physician William Osler, North America's leading medical teacher, whom McEachran had invited to teach at the College in 1876 in addition to his duties in the faculty of medicine. Osler had studied with Virchow in Berlin and applied his methods of autopsy technique and of scientific inquiry to his teaching of both human and veterinary pathology at McGill. Osler also undertook investigations into various diseases of domestic animals, at the request of McEachran, who doubled as Chief Veterinary Inspector for the Dominion Department of Agriculture. Osler left McGill University in 1884. Only after that year did other North American veterinary schools adopt pathology as a discipline of instruction. However, by 1884, Osler had already left his indelible imprint on the students (both medical and veterinary) he had taught in Montreal, one of whom took over the teaching of pathology in the veterinary college. Another, who followed Osler's example and also studied in Berlin with Virchow, wrote the first book in the English language on veterinary post mortem technique in 1889.(ABSTRACT TRUNCATED AT 400 WORDS)

A history of the Pathological Division of the Bureau of Animal Industry, United States Department of Agriculture, between 1891-1921.

As part of a continuing historical study of the evolution of the discipline of veterinary pathology in North America, this paper relates the role played by the Pathological Division of the Bureau of Animal Industry (BAI), formerly a unit of the United States Department of Agriculture. The work of this division of the BAI during its first three decades is examined with respect to its leadership, activities and attainments, and these are compared with similar activities in veterinary colleges and state experiment stations in the United States and in foreign veterinary colleges and research establishments. The Pathological Division devoted a good deal of its efforts to the production of biologic prophylactic products, with resounding success in controlling blackleg and other diseases. Its other activities were in laboratory diagnostic work and in research into animal diseases. The picture that emerges in those spheres is of an organizational unit that despite its name, made little use of the approaches and methods of pathology, but rather availed itself of the tools of microbiology whether or not these were appropriate. In so doing, it lagged considerably behind the comparable institutions both in the United States and abroad.

Virchow's contributions to veterinary medicine: celebrated then, forgotten now.

In 1858, Rudolf Virchow, the professor of pathology in Berlin University, published the book "Cellular Pathology". A compendium of his lectures to physicians and medical students, he introduced the use of microscopy for the study of human diseases. To an astonishing extent Rudolf Virchow was helpful to the disciplines of veterinary medicine (and veterinary pathology). Considered a scientific genius in several disciplines, this essay deals exclusively with the devotion of Virchow, a scholarly physician, to the profession of veterinary medicine. He respected veterinary research, supported governmental veterinary education, and provided a role model for the veterinarians who were drafting control legislation of contagious diseases in livestock. Repeatedly, he responded in help when seemingly irretrievable problems arose. Examples of Virchow's activities in the realms of veterinary medicine and pathology are marshalled here to shed light on this pioneer "veterinary pathologist". In celebration of 50 years of the American College of Veterinary Pathologists in 1999, it is timely to remember that Rudolf Virchow, the father of cellular pathology, also fathered veterinary pathology, whose offsprings in Canada and the U.S.A. (Osler, Clement, Williams, Olafson, Jones) had enabled them to form and foster the A.C.V.P.

Heavy metal nephropathy of rodents.

Heavy metal nephropathy is a pathologic entity of the renal tubular epithelium of rats, evoked by lead, gold, and other heavy metals. It is characterized acutely by coagulative necrosis, subacutely by cortical fibrosis, and chronically by cytomegaly and karyomegaly. Finally, adenomas develop, some of which become malignant.

The effect of longterm treatment with auranofin and gold sodium thiomalate on immune function in the dog.

Although gold compounds are recognized as effective immunomodulatory agents in the treatment of rheumatoid arthritis (RA), their mechanism of action is controversial. We examined the effect of longterm treatment with 0.6-3.6 mg/kg auranofin (AF) per os q24h, or intramuscular injections of 0.5-2.0 mg/kg gold sodium thiomalate (GSTM) q3d, on 13 variables of immune function in normal dogs. None of the changes in these variables previously attributed to treatment with AF or GSTM could be demonstrated after 6-7 years' dosing. As gold compounds are effective in treating spontaneous RA in dogs, these proposed actions may not be responsible for the remittive effects of chrysotherapy in this disease.

Carcinogenicity study of auranofin, an orally administered gold compound, in mice.

Auranofin, a gold-containing compound, was administered to Charles River CD-1 mice for 18 months to assess its possible carcinogenicity. The mice were dosed orally with 1.0, 3.0, or 6.0 (increased to 9.0 on Day 294) mg/kg/day. Each dose group and each of two control groups contained 110 males and 110 females. Survival was greater than 70% at the end of the study. No effect of the treatment on neoplastic or nonneoplastic lesions was found. This is in contrast to the results reported in rats. Auranofin in rats produced a heavy metal nephropathy characterized by acute coagulative necrosis, subacute renal cortical fibrosis, chronic cytomegaly and karyomegaly, and finally renal cortical neoplasia (adenomas and adenocarcinomas). The lack of effect of auranofin on tumor incidence in mice suggests the findings in rats may be species specific.

Gold-induced immune thrombocytopenia in the dog.

In two seven-year studies with gold compounds in dogs of both sexes, thrombocytopenia was observed after 45 to 72 months of dosing in three of 14 and two of 14 dogs in high-dose groups that received 2.4 to 3.6 mg/kg of auranofin per day orally or 0.5 to 2.0 mg/kg of gold sodium thiomalate intramuscularly once every three days, respectively. An immune basis for the disorder was suggested by the apparent consumptive nature of the thrombocytopenia (increased bone marrow megakaryocytes and large peripheral blood platelets), the response to corticosteroid therapy and the demonstration of increased platelet-associated immunoglobulin. The latter was demonstrated with a solid phase radioimmunoassay and by electron microscopy using a staphylococcal protein A-colloidal gold conjugate. Platelet-associated immunoglobulin decreased as the platelet counts rose, and in one dog monitored over periods of steroid-induced remissions and subsequent relapses, the amount of platelet-associated immunoglobulin G correlated inversely with the platelet count (r = 0.82). These findings suggest that the long-term administration of gold compounds in dogs is associated with a dose-dependent incidence of thrombocytopenia, which is immune-mediated and similar to that associated with parenteral chrysotherapy in man. The application of tests for platelet-associated immunoglobulin to canine patients with immune thrombocytopenia should be useful in the diagnosis of the disorder in clinical practice.

Arterial medial necrosis and hemorrhage induced in rats by intravenous infusion of fenoldopam mesylate, a dopaminergic vasodilator.

Fenoldopam mesylate, a selective, postsynaptic, dopaminergic vasodilator, was administered to rats for assessment of its clinical, toxicologic, and pathologic effects. Groups of 8 male and 8 female rats received 5, 25, 50, or 100 micrograms/kg/min by intravenous infusion for 24 hours. Groups of 12 male and 12 female rats received 2, 8, 16, or 20 mg/kg/day by intravenous injection once daily for 12 days. Tissues were examined by light microscopy. Rats infused for 24-hours with 5-100 micrograms/kg/min of fenoldopam had lesions of renal and splanchnic arteries characterized by medial necrosis and hemorrhage. None were seen in control rats or those administered the compound by intravenous injection. Arteries with four to five layers of medial smooth-muscle cells were most severely and frequently affected. Lesions were particularly severe in interlobular pancreatic arteries and subserosal gastric arteries. They occurred first at 4 hours, were present at low incidence at 8 hours, were induced in unrestrained rats, and were not caused by the experimental procedures employed. The nature and disposition of this novel arterial lesion in the rat suggests that its pathogenesis may be related to the pharmacologic activity of fenoldopam mesylate at the dopamine receptor.