Raccoon ascarid larvae (Baylisascaris procyonis) as a cause of ocular larva migrans.

Larvae of the common raccoon roundworm, Baylisascaris procyonis, are known causes of visceral larva migrans and CNS disease in animals and human beings. In the present experiments we examined the ability of B. procyonis to cause ocular larva migrans (OLM) in subhuman primates, as an indication of its possible ocular zoonotic importance. Squirrel monkeys given 5,000 or 10,000 infective B. procyonis eggs per os and cynomolgus monkeys given 20,000 eggs had clinical and histologic evidence of OLM, beginning 7 days after inoculation. Clinically, multifocal retinal hemorrhages, white spots, chorioretinitis, inflammatory tracks, vascular sheathing, diffuse retinal degeneration, and motile intraretinal larvae were seen. Histologically, primarily subretinal larvae caused varying degrees of retinal disruption, degeneration and necrosis, retinitis, vasculitis, and perivascular sheathing, primarily with eosinophils. Larvae were also present in choroidal granulomas. It was concluded that B. procyonis larvae have marked ability to produce OLM in subhuman primates following oral infection and should be considered as a possible etiology in human ocular disease.

Teratogenicity of 3,3-dimethyl-1-phenyltriazene: distribution in rats and rat embryos.

3,3-Dimethyl-1-phenyltriazene (DMPT) is a methylating agent which is carcinogenic, teratogenic and mutagenic which, in the rat, provides a reproducible animal model with which to study the basis of chemically-induced micrognathism. The basis of teratogenic organotropism of DMPT and other methylating teratogens is unknown. The present study was undertaken to determine if limited chemical distribution within the embryo was responsible for the organotropism of DMPT. Whole-embryo autoradiographs and liquid scintillation analysis indicated that although DMPT may have some limitations of chemical distribution within the embryo, these limitations are not sufficient to explain its teratogenic organotropism.

Histopathology of nymphal pentastomid infections (Sebekia mississippiensis) in paratenic hosts.

The histopathologic alterations occurring in mice, hamsters, turtles, and a frog were described following experimental infection with nymphs of Sebekia mississippiensis. Initially, nymphal migration caused traumatic tissue damage and hemorrhage characteristic of larva migrans. Subsequent inflammatory responses included cellular infiltration with eosinophils, macrophages, and lymphocytes, and fibrotic encapsulation of the nymphs. Dead nymphs were surrounded by a necrotic granulomatous response similar to that reported previously in humans and other animals. Differences were not seen in animals given single or multiple infections, but mice and hamsters exhibited a more marked inflammatory response than turtles. Overall, the histopathologic response to nymphal infections resembled those seen in infections resulting from ingestion of eggs, and both sources of infection should be considered in epidemiologic investigations of naturally occurring pentastomiasis.

Experimental infection of domestic swine with Baylisascaris procyonis from raccoons.

Six 8-week-old ascarid-naive pigs which were experimentally infected with 72,000 embryonated Baylisascaris procyonis eggs of raccoon origin developed lesions limited to the intestines and liver. Intestinal lesions consisted of multifocal areas of inflammation by macrophages, eosinophils, and lymphocytes in the mucosa and submucosa, in association with Baylisascaris larvae; similar lesions were seen in the mesenteric lymph nodes. Typical white, granulation type, multifocal interstitial hepatitis ("milk-spots"), 1 to 5 mm in diameter, were seen in the livers by 7 days, with resolution by 47 days. Microscopically, these consisted of multifocal areas of marked periportal and interlobular edema, and influx of eosinophils, and large intralobular aggregates of eosinophils. At 47 days, hundreds to thousands of small white granulomas were seen on the serosa of the intestines; microscopically, they were discrete collections of macrophages, lymphocytes, and eosinophils in the submucosa and muscle layers surrounding nonviable remnants of Baylisascaris larvae. Larvae or lesions were not seen in other tissues, including the brain. These experiments indicated that B procyonis will undergo limited migration in swine and can produce typical white spots in the liver. The larvae were killed by cellular reactions in the intestinal wall and liver, and, unlike the situation in most other animals infected with this parasite, no somatic migration or CNS disease occurred after infection.

Pathology of pentastomid infections (Sebekia mississippiensis) in fish.

Differential pathogenesis was observed in two species of fish naturally infected with the pentastome Sebekia mississippiensis. Mosquitofish (Gambusia affinis) showed a mild inflammatory response to developing nymphs, whereas swordtails (Xiphophorus helleri) had an extensive granulomatous inflammatory reaction with accompanying hemorrhage, myositis, and myodegeneration. This suggested that certain species of tropical fish reared in the southeastern United States may be at risk to potentially harmful infections with this parasite.

Ocular, naso-maxillary, and neural anomalies in raccoons, Procyon lotor (L.).

Congenital ocular and related anomalies were studied in two unrelated young raccoons. One animal was anophthalmic and had severe anomalies of the central nervous system, consisting of meningoencephalocele, pachygyria, hydranencephaly, cerebellar cavitation, syringomyelia, and other defects. A second animal was microphthalmic with congenital defects of the nose, maxilla and teeth. Ocular lesions were severe and included chorioretinal coloboma, retinal folds, disorganized neuroectodermal cell layers, spherophakia, cataract and other defects. The nose had unilateral abnormal epithelium, hair follicles, sweat glands and sebaceous glands, and a lack of parietal cartilage on the affected side.

Pancreatic abscess in dogs: six cases (1978-1986).

Pancreatic abscess was diagnosed by exploratory celiotomy in 6 dogs. The most common clinical signs included acute onset of lethargy (n = 5), anorexia (n = 6), vomiting (n = 5), and diarrhea (n = 2). Physical examination revealed pain response to abdominal palpation (n = 5), depression (n = 5), icterus (n = 3), fever (n = 3), and cranial abdominal mass (n = 2). Consistent preoperative clinicopathologic abnormalities included leukocytosis with left shift, observance of toxic neutrophils on the blood smear, hyperlipasemia, hyperamylasemia, hyperbilirubinemia, and increased serum alkaline phosphatase activity. In 5 of 6 dogs, abdominal radiography revealed increased soft tissue density in the cranial portion of the abdomen. Ultrasonography performed on 4 dogs confirmed pancreatic mass. In all dogs, exploratory celiotomy revealed a cavitary pancreatic mass that contained sterile, mucopurulent material. Histopathologic diagnoses included acute necrotizing or chronic-active pancreatitis and steatitis. Two dogs were euthanatized at the time of diagnosis, and the remaining 4 were treated by use of pancreatic debridement(s), open abdominal drainage, and intensive administration of fluids and antibiotics. One dog was euthanatized 4 days after surgery, because of progressive pancreatic abscessation. Three dogs recovered and were discharged.

Cerebrospinal nematodiasis and visceral larva migrans in an Australian (Latham's) brush turkey.

Cerebrospinal nematodiasis and visceral larva migrans were diagnosed in an Australian (Latham's) brush turkey (Alectura lathami) that died at the Indianapolis Zoo following a progressive neurologic disease. Histologically, multifocal areas of malacia, necrosis, and inflammation were seen in sections of cerebrum, cerebellum, and midbrain; lesions were most severe in the cerebellum. A large granuloma in a lung contained cross sections of a large ascarid larva identified as Baylisascaris. The CNS lesions were typical of larval migration, as documented in other avian species. An epizootiologic investigation indicated that Baylisascaris procyonis was the etiologic agent and that the bird had acquired the parasite through contact with fecal contamination from wild raccoons at the St Louis Zoo, where the bird had been raised.

Fatal cerebrospinal disease caused by Baylisascaris procyonis in domestic rabbits.

Infection with Baylisascaris procyonis, the common roundworm of raccoons, was found to be the cause of an epizootic of fatal CNS disease in domestic rabbits (Oryctolagus cuniculus). Clinical signs included torticollis, ataxia, tremors, and falling. Gross lesions were limited to white, raised nodules (1 to 1.5 mm) on the epicardium, endocardium, and liver serosa, and they were found to be larval granulomas. Microscopic lesions included multifocal myocarditis, multifocal hemorrhagic tracks and associated necrosis and inflammation in the liver, multifocal eosinophilic myositis, focal nephritis, and mild interstitial pneumonia; larval granulomas were seen in the heart, liver, lung, and mandibular salivary gland. Lesions in the brain consisted of multifocal areas of necrosis and inflammation in the cerebrum, cerebellum, midbrain, and medulla, with accompanying perivascular leukocyte aggregates and neuronal and axonal degeneration. Large numbers of large ascarid larvae were seen in the brain. Epidemiologically, infection was linked to the use of contaminated straw from a barn used by raccoons. On the basis of this study as well as that of similar studies, it was concluded that barn use and contamination by raccoons may be an important source of infection of animals and possibly man with this parasite.

Teratogenicity of 3,3-dimethyl-1-phenyltriazene in the rat: gross malformations including micrognathism.

3,3-Dimethyl-1-phenyltriazene (DMPT), an alkylating agent, has been reported to be teratogenic in chickens, mice, and rats. One of the most commonly affected structures is the mandible; however, a complete description and incidence rates of all malformations produced have not been published. Rats were treated on day 12 of gestation (day 0 = sperm in vaginal smear) with a single intraperitoneal injection of 30 mg DMPT/kg. Fetuses were examined on each subsequent day of gestation for external and skeletal abnormalities. Standard soft tissue examinations were performed on day-20 fetuses. A high percentage (greater than or equal to 80%) of treated litters contained numerous fetuses with micrognathism, cleft palates, syndactyly, adactyly, and misshapen digits and limbs. Lordosis, cerebellar and cerebral hypoplasia, decreased fetal size, and generalized delayed ossification were also observed. Dams exposed to DMPT had decreased food consumption and weight gains, although clinicopathologic and histopathologic evaluations failed to indicate other evidence of maternal toxicity. DMPT caused numerous permanent structural alterations that were not attributed to maternal toxicity.

Sequential ultrastructural changes of the pancreas in zinc toxicosis in ducklings.

The sequential ultrastructural alterations of the pancreas in zinc toxicosis were examined in ducklings fed 2500 ppm Zn (as ZnSO4) for 56 days. From days 3 to 17, acinar cells had cytoplasmic vacuoles that contained electron-dense, zymogen-like material and increased autophagocytosis. Other changes were swollen mitochondria and dilatation, vesiculation, degranulation and intracisternal sequestration of rough endoplasmic reticulum. Apoptosis was the predominant form of cell deletion. By day 10, acinar cellular atrophy and interstitial fibrosis were noted. Islets appeared normal. After day 19, the pancreas consisted of ductlike structures embedded in fibrous connective tissue with a minimal inflammatory cell response. These ductlike structures were lined by attenuated to cuboidal, atrophic acinar cells. Many cells contained granular, electron-dense cytoplasmic debris that served as a marker of previous cell damage. This ultrastructural study provides support for a previously proposed theory that ductlike structures (tubular complexes) arise by atrophy and dedifferentiation of acinar cells.

Histologic characterization of the thymus in canine X-linked severe combined immunodeficiency.

This study describes the thymic morphology in 52 dogs (ranging in age from 1 to 79 days) with X-linked severe combined immunodeficiency disease (XSCID). The thymuses from the XSCID dogs and age-matched controls were evaluated histologically for the presence of Hassall's corpuscles and branchial duct remnants, the degree of corticomedullary differentiation, and lymphoid development and organization. Within this population of XSCID dogs with the same genetic defect, three histologic patterns of thymic dysplasia were recognized. Simple dysplasia, noted in 27 XSCID thymuses, was characterized by varying numbers of lymphocytes, no corticomedullary demarcation, and an absence of Hassall's corpuscles. Dysplasia with Hassall's corpuscles was noted in 21 dogs and consisted of varying numbers of lymphocytes, no corticomedullary demarcation, and varying numbers of Hassall's corpuscles. Dysplasia with partial corticomedullary demarcation, noted in 4 dogs, consisted of relatively normal-looking thymuses with well-defined corticomedullary demarcation and numerous Hassall's corpuscles; however, the lobules were extremely small and the subcapsular cortical region was devoid of lymphocytes. Cystic branchial duct remnants were present in 46 of the 52 XSCID thymuses and were more numerous in those thymuses with the pattern of simple dysplasia. The thymuses of XSCID pups less than 4 weeks of age were of the simple dysplastic type and thymuses of XSCID dogs greater than 4 weeks of age were more developed, as evidenced by increased numbers of Hassall's corpuscles and greater corticomedullary demarcation. In conclusion, the thymic dysplasia and lymphoid hypoplasia associated with X-linked severe combined immunodeficiency disease in the dog does not appear to be due to a developmental arrest but rather due to an active process dependent on factors probably related to the overall genetic defect.

The raccoon ascarid. A probable cause of human ocular larva migrans.

The ability of raccoon roundworm larvae, Baylisascaris procyonis, to produce ocular larva migrans (OLM) was studied in various experimental animals. In addition, the clinical and pathologic lesions were compared to those in suspected cases of human ocular baylisascariasis, in patients with diffuse unilateral subacute neuroretinitis (DUSN). Ocular larva migrans was produced in squirrel monkeys, cynomolgus monkeys, mice, hamsters, grey squirrels, and woodchucks orally infected with B. procyonis eggs. The clinical and histologic lesions were primarily those of retinitis, retinal hemorrhages, retinal tracks, disruption, and vasculitis; pigment migration; choroiditis; vitritis; and free or encysted larvae in ocular and extraocular tissues. The lesions of experimental OLM correlated well with those of suspected cases of human ocular baylisascariasis and DUSN. Based on these studies, B. procyonis of raccoons should be considered as a probable cause of OLM and DUSN in humans.

Teratogenicity of 3,3-dimethyl-1-phenyltriazene in the rat: histopathologic and ultrastructural alterations.

3,3-Dimethyl-1-phenyltriazene (DMPT) is a methylating agent which is teratogenic, carcinogenic, and mutagenic. A single intraperitoneal injection of 30 mg DMPT/kg given to pregnant rats on day 12 of gestation produces malformations with minimal maternal toxicity. Malformations include skeletal deformities such as micrognathism, cleft palate, and digital malformations, as well as central nervous system hypoplasia. The purpose of the present study was to characterize the light and electron microscopic alterations produced by DMPT. Electron microscopy (EM) revealed that at 4 hr postinjection of DMPT, rare cells of the neural tube contained few membrane-bound aggregations of organelles and condensed chromatin; this change was consistent with apoptosis, a type of cell death characterized by morphologic and biochemical alterations distinct from necrosis. At 8 hr postinjection, apoptosis was more prominent in the neural tube and also observed in the mandibular process. At 16 hr postinjection, numerous apoptotic cells were interspersed with unaffected cells that contained phagocytized apoptotic bodies. Light microscopic examination of DMPT-exposed conceptuses showed apoptosis in the neural tube at 24 hr postinjection. Forty-eight hours postinjection, apoptosis, in decreasing order of severity, was observed in the neural tube, craniofacial processes, limb buds, and somites and liver. Apoptosis was absent in all tissues by 72 hr postinjection. Nervous tissues failed to achieve proper histologic organization, but all other tissues appeared microscopically normal from 72 hr postinjection until the end of gestation. There appeared to be some degree of tissue specificity to the effects of DMPT.

Effects of flunixin meglumine on dogs with experimental gastric dilatation-volvulus.

Gastric dilatation-volvulus (GDV) was created experimentally and maintained for 90 minutes in 16 anesthetized, mixed-breed dogs. After the GDV was corrected, normal saline solution (0.044 mL/kg intravenously [IV]) was administered to eight dogs (controls), and flunixin meglumine (2.2 mg/kg IV) was administered to eight dogs. Microspheres labeled with radioactive cobalt, scandium, tin, or niobium were injected intravenously at baseline (before GDV) and minutes 90, 100, and 270, respectively, to determine tissue blood flows. Plasma endotoxin and prostacyclin were measured at the same intervals. Electrocardiogram, mean arterial pressure, portal pressure, and cardiac output were recorded continuously. Dogs were euthanatized at minute 270 and necropsied. There was no significant difference between treatment groups for any measured variable at any time. Endotoxin levels increased significantly during GDV. Prostacyclin levels were lower in dogs treated with flunixin meglumine than in controls at minutes 210 and 270. Histopathologic findings were similar for all dogs and consistent with those associated with endotoxemia. Flunixin meglumine treatment did not alter cardiac indices or tissue blood flows significantly. However, elevation of prostacyclin was inhibited by flunixin meglumine, which suggested that continued effects of endotoxic damage might be attenuated or inhibited.

Pathologic features of naturally occurring juvenile polyarteritis in beagle dogs.

Eighteen young Beagle dogs (eight males and 10 females), ages 6-40 months, with canine juvenile polyarteritis syndrome (CJPS), a naturally occurring vasculitis and perivasculitis of unknown etiology, were necropsied, and their tissues were examined by histopathologic and histochemical methods. The condition is characterized by recurring episodes of an acute onset of fever (> 40 C) and neck pain that persist for 3-7 days. The major histopathologic alterations were a systemic vasculitis and perivasculitis. During the febrile, painful period of CJPS, the vascular lesions ranged from a histiocytic-lymphocytic periarterial infiltration to transmural arterial inflammation with concomitant fibrinoid necrosis and vascular thrombosis. Massive periarterial accumulations of inflammatory cells were common and often extended into adjacent tissues. The small- to medium-sized muscular arteries of the heart, cranial mediastinum, and cervical spinal meninges were consistently involved. Vasculitis occasionally occurred in other organ systems. The vascular lesions in dogs examined during clinically normal periods consisted of intimal and medial fibrosis, ruptured elastic laminae, and mild perivasculitis; these lesions were probably related to previous episodes of vasculitis. Eight dogs that had experienced repeated acute episodes also developed splenic, hepatic, and renal amyloidosis. The clinical signs, laboratory abnormalities, and the vascular lesions suggest that the condition may be immune-system mediated. CJPS may serve as a naturally occurring animal model of human immune-system-mediated vasculitides such as polyarteritis nodosa, infantile polyarteritis, and Kawasaki disease.