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The physiology of males and females can be vastly different, complicating interpretation of toxicological and physiological data. The objectives of this study were to elucidate the sex differences in the microbiome-gastrointestinal (GI) transcriptome of adult zebrafish. We compared microbial composition and diversity in both males and females fed the same diet and housed in the same environment. There were no sex-specific differences in weight gain nor gastrointestinal morphology based on histopathology. There was no difference in gut microbial diversity, richness (Shannon and Chao1 index) nor predicted functional composition of the microbiome between males and females. Prior to post-hoc correction, male zebrafish showed higher abundance for the bacterial families Erythrobacteraceae and Lamiaceae, both belonging to the phyla Actinobacteria and Proteobacteria. At the genus level, Lamia and Altererythrobacter were more dominant in males and an unidentified genus in Bacteroidetes was more abundant in females. There were 16 unique differentially expressed transcripts in the gastrointestinal tissue between male and female zebrafish (FDR corrected, p < 0.05). Relative to males, the mRNA expression for trim35-9, slc25a48, chchd3b, csad, and hsd17b3 were lower in female GI while cyp2k6, adra2c, and bckdk were higher in the female GI. Immune and lipid-related gene network expression differed between the sexes (i.e., cholesterol export and metabolism) as well as networks related to gastric motility, gastrointestinal system absorption and digestion. Such data provide clues as to putative differences in gastrointestinal physiology between male and female zebrafish. This study identifies host-transcriptome differences that can be considered when interpreting the microgenderome of zebrafish in studies investigating GI physiology and toxicology of fishes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dietary exposure to chemicals alters the diversity of microbiome communities and can lead to pathophysiological changes in the gastrointestinal system. The organochlorine pesticide dieldrin is a persistent environmental contaminant that bioaccumulates in fatty tissue of aquatic organisms. The objectives of this study were to determine whether environmentally-relevant doses of dieldrin altered gastrointestinal morphology and the microbiome of zebrafish. Adult zebrafish at ∼4 months of age were fed a measured amount of feed containing either a solvent control or one of two doses of dieldrin (measured at 16, and 163.5 ng/g dry weight) for 4 months. Dieldrin body burden levels in zebrafish after four-month exposure were 0 (control), 11.47 ± 1.13 ng/g (low dose) and 18.32 ± 1.32 ng/g (high dose) wet weight [mean ± std]. Extensive histopathology at the whole organism level revealed that dieldrin exposure did not induce notable tissue pathology, including the gastrointestinal tract. A repeated measure mixed model analysis revealed that, while fish gained weight over time, there were no dieldrin-specific effects on body weight. Fecal content was collected from the gastrointestinal tract of males and 16S rRNA gene sequencing conducted. Dieldrin at a measured feed dose of 16 ng/g reduced the abundance of Firmicutes, a phylum involved in energy resorption. At the level of class, there was a decrease in abundance of Clostridia and Betaproteobacteria, and an increase in Verrucomicrobiae species. We used a computational approach called predicted relative metabolomic turnover (PRMT) to predict how a shift in microbial community composition affects exchange of metabolites. Dieldrin was predicted to affect metabolic turnover of uroporphyrinogen I and coproporphyrinogen I [enzyme]-cysteine, hydrogen selenide, selenite, and methyl-selenic acid in the fish gastrointestinal system. These pathways are related to bacterial heme biosynthesis and selenium metabolism. Our study demonstrates that dietary exposures to dieldrin can alter microbiota composition over 4 months, however the long-term consequences of such impacts are not well understood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

To improve physical characteristics of plastics such as flexibility and durability, producers enrich materials with phthalates such as di-2-(ethylhexyl) phthalate (DEHP). DEHP is a high production volume chemical associated with metabolic and immune disruption in animals and humans. To reveal mechanisms implicated in phthalate-related disruption in the gastrointestinal system, male and female zebrafish were fed DEHP (3 ppm) daily for two months. At the transcriptome level, DEHP significantly upregulated gene networks in the intestine associated with helper T cells' (Th1, Th2, and Th17) specific pathways. The activation of gene networks associated with adaptive immunity was linked to the suppression of networks for tight junction, gap junctional intercellular communication, and transmembrane transporters, all of which are precursors for impaired gut integrity and performance. On a class level, DEHP exposure increased Bacteroidia and Gammaproteobacteria and decreased Verrucomicrobiae in both the male and female gastrointestinal system. Further, in males there was a relative increase in Fusobacteriia and Betaproteobacteria and a relative decrease in Saccharibacteria . Predictive algorithms revealed that the functional shift in the microbiome community, and the metabolites they produce, act to modulate intestinal adaptive immunity. This finding suggests that the gut microbiota may contribute to the adverse effects of DEHP on the host by altering metabolites sensed by both intestinal and immune Th cells. Our results suggest that the microbiome-gut-immune axis can be modified by DEHP and emphasize the value of multiomics approaches to study microbiome-host interactions following chemical perturbations.

Background: Cercopithifilaria bainae is a tick-vectored filarioid nematode associated with erythematous dermatitis in dogs. It has not been reported previously in the United States., Hypothesis/objective: To describe clinical, histological and parasitological diagnosis and treatment of C. bainae in a dog., Animals: An 11-month-old golden retriever/standard poodle mixed breed dog from Florida (USA)., Methods and Materials: The dog had no travel history within or outside the United States, was presented with a one month history of annular erythematous plaques on the head and ulcers on the medial canthi. Lesions were unresponsive to antibiotic treatment., Results: Histopathological evaluation of skin biopsies revealed an eosinophilic to lymphohistiocytic perivascular dermatitis with multiple microgranulomas and rare 5-10 μm diameter microfilariae within microgranulomas. Microfilarial morphology was consistent with C. bainae. PCR and sequencing of 18S rRNA and mitochondrial cytochrome oxidase subunit I genes confirmed the nematodes as C. bainae. The dog was treated with a commercial spot-on containing imidacloprid and moxidectin, and clinical resolution occurred., Conclusions and Clinical Importance: To the best of the authors' knowledge, this is the first report of C. bainae in a dog in the United States and the first description of dermatological lesions caused primarily by C. bainae., (© 2018 ESVD and ACVD.)

Watercraft-related trauma is the predominant cause of human-induced mortality in manatees (Trichechus manatus latirostris), a federal- and state-listed endangered species. Pyothorax (documented in this case report) and other secondary infections are common sequelae of inhalation of water and the open wounds caused by boat propellers. These secondary infections can lead to the demise of the animal weeks to months after the traumatic incident when external wounds have healed. Diagnosis of underlying disease on physical examination during capture and restraint can be difficult. Acute phase proteins, including serum amyloid A, fibrinogen, and albumin can be used to diagnose inflammatory disease in manatees and improve quality of medical care and husbandry. We also provide the first report of polycystic kidneys in Sirenians.

Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.

Two young adult dogs with gastrointestinal signs were each found to have an intra-abdominal mass based on physical examination and diagnostic imaging. On exploratory laparotomy, small intestinal masses and mesenteric lymphadenopathy were found in both dogs; a liver mass was also found in dog 1. Cytologic and histologic examination of intestinal and liver masses and mesenteric lymph nodes revealed 2 distinct lymphoid cell populations: lymphoblasts and atypical Mott cells. With Romanowsky stains, the atypical Mott cells contained many discrete, clear to pale blue cytoplasmic inclusions consistent with Russell bodies that were positive by immunohistochemistry for IgM and CD79a in both dogs and for IgG in dog 2. The Mott cells and occasional lymphoblasts stained strongly positive with periodic acid-Schiff. Using flow cytometric immunophenotyping in dog 1, 60% of peripheral blood mononuclear cells and 85% of cells in an affected lymph node were positive for CD21, CD79a, IgM, and MCH II, indicative of B-cells. With electron microscopy, disorganized and dilated endoplasmic reticulum was seen in Mott cells in tumors from both dogs. Antigen receptor gene rearrangement analysis of lymph node and intestinal masses indicated a clonal B-cell population. Based on cell morphology, tissue involvement, and evidence for clonal B-cell proliferation, we diagnosed neoplasms involving Mott cells. To the authors' knowledge, this is the second report of Mott cell tumors or, more appropriately, B-cell lymphoma with Mott cell differentiation, in dogs. More complete characterization of this neoplasm requires further investigation of additional cases. This lymphoproliferative disease should be considered as a differential diagnosis for canine gastrointestinal tumors.

An endobronchial polyp was visible radiographically and bronchoscopically in an 11-year-old, mixed-breed dog with a persistent cough. The polyp was removed by traction. Initial histological examination suggested it was a myxomatous fibroma. The cough resolved but recurred with polyp regrowth. Two additional lung masses became visible radiographically. The polyp was removed twice more at 6-month intervals. Euthanasia was performed 15 months after first presentation when coughing recurred soon after the final bronchoscopy. Histological examination revealed that the mass was a myxomatous sarcoma. The lung contained two other unrelated tumors: a bronchioloalveolar carcinoma and a carcinoma of unknown origin.

Objective: To evaluate the efficacy of a percutaneously controlled hydraulic occluder (HO) in a rat model of gradual venous occlusion., Study Design: Experimental study., Animals: Ten male Sprague-Dawley rats., Methods: HOs and perivascular transit time ultrasound flow probes were applied to the caudal vena cava (CVC). Occluders in group I rats (n=6) were gradually attenuated over 8 weeks, whereas occluders in group II rats (n=4) were not attenuated. Vena caval blood flow measurements were performed weekly in all rats for 8 weeks. After euthanasia, the CVC was evaluated grossly and by histopathology., Results: Premature occlusion of the vena cava occurred during the 1st week in 3 rats (1 in group I, 2 in group II) because of kinking of the vena cava between the HO and the flow probe. For the remaining rats, mean blood flow in group I decreased significantly from 40.71 mL/min/kg at baseline to 4.68 mL/min/kg at 8 weeks (P=.0094, power=0.91). Group II rats maintained vena caval blood flow at all times during the study. Complete occlusion of the vena cava was confirmed at necropsy in all group I rats., Conclusions: Gradual occlusion of the CVC of rats was achieved with HOs over 8 weeks. This model is limited by the size of the experimental animals and comparatively large implants., Clinical Relevance: HOs may provide a method for gradual occlusion of congenital portosystemic shunts.

In September and October 2002, an epizootic of neurologic disease occurred at an alligator farm in Florida (USA). Three affected American alligators (Alligator mississippiensis) were euthanatized and necropsied, and results confirmed infection with West Nile virus (WNV). The most significant microscopic lesions were a moderate heterophilic to lymphoplasmacytic meningoencephalomyelitis, necrotizing hepatitis and splenitis, pancreatic necrosis, myocardial degeneration with necrosis, mild interstitial pneumonia, heterophilic necrotizing stomatitis, and glossitis. Immunohistochemistry identified WNV antigen, with the most intense staining in liver, pancreas, spleen, and brain. Virus isolation and RNA detection by reverse transcription-polymerase chain reaction confirmed WNV infection in plasma and tissue samples. Of the tissues, liver had the highest viral loads (maximum 10(8.9) plaque-forming units [PFU]/0.5 cm3), whereas brain and spinal cord had the lowest viral loads (maximum 10(6.6) PFU/0.5 cm3 each). Virus titers in plasma ranged from 10(3.6) to 10(6.5) PFU/ml, exceeding the threshold needed to infect Culex quinquefasciatus mosquitoes (10(5) PFU/ml). Thus, alligators may serve as a vertebrate amplifying host for WNV.

A 9-year-old Golden Retriever that had undergone left total hip arthroplasty 6 years previously was evaluated because of constipation and tenesmus. Abdominal radiography and ultrasonography revealed a large intrapelvic mass that was contiguous with a mass of polymethyl methacrylate that had been extruded through a defect in the medial wall of the acetabulum at the time of total hip arthroplasty. Clinical signs resolved following resection of the mass and associated polymethyl methacrylate from the pelvic canal. Results of histologic examination of the mass were consistent with a diagnosis of foreign body granuloma, most likely secondary to particulate debris. There was no clinical or radiographic evidence of aseptic loosening of the acetabular or femoral components, and the mass may have represented a response to wear debris.

Interferon gamma-knockout mice were challenged with 5000 Sarcocystis neurona sporocysts acquired from a naturally infected opossum. Ponazuril was administered once, by gavage, at day 1, 3, 7, 10, or 14 post-infection (pi). Ponazuril was given at either 20 or 200mg/kg. Mice that survived to day 30 pi were euthanized. Severity of CNS infection was quantified as schizont density in the cerebellum. Unchallenged mice in treatment and non-treatment groups remained free of disease and gained weight throughout the experiment. All challenged mice, regardless of treatment, developed histologic evidence of CNS infection even though clinical signs were prevented in some groups. The greatest treatment benefits were seen in mice given 200mg/kg ponazuril between days 4 and 14 pi. Weight gain over the course of the experiment occurred only in mice that were given 200mg/kg ponazuril on day 7 or 10 pi. With the exception of groups given 200mg/kg ponazuril on day 7 or 14 pi, mice in groups that got sporocysts developed abnormal neurologic signs. No deaths before day 30 pi occurred in mice given ponazuril at 20mg/kg on day 7 pi or 200mg/kg on day 1, 7, 10, or 14 pi. This effect was not significant. Mice given 200mg/kg on day 7 pi had significantly fewer cerebellar schizonts than did those of the control group that was not given ponazuril. These results indicate that single-dose administration of ponazuril for prevention of CNS infection is partially protective when given between days 4 and 14 pi.

The current report describes a malignant melanoma in the dermis of a 13-year-old bay Thoroughbred mare. Microscopic examination revealed that tumor cells were arranged in cords and packets within an abundant collagenous stroma containing scattered myxomatous foci. Tumor cells stained positively for S-100, neuron-specific enolase, and vimentin and some contained melanin granules. Some clusters of tumor cells were also positive for pancytokeratin. Expression of epithelial cell markers has been described in small numbers of human melanomas but has not been reported previously in equine melanomas.

Fifteen gamma-interferon gene knockout mice were each orally inoculated with 5 x 10(3) Sarcocystis sporocysts derived from Virginia opossums (Didelphis virginiana) fed nine-banded armadillo (Dasypus novemcinctus) muscle containing sarcocysts. Three mice were inoculated with similarly obtained homogenates, but in which no sporocysts were detected. Mouse M8 was pregnant when inoculated and gave birth during the trial. Fifteen of 15 (100%) mice inoculated with sporocysts developed neurologic signs and/or died by day 30 d.p.i. One of 3 (33.3%) mice inoculated with homogenates in which no sporocysts were detected developed clinical signs and died at 34 d.p.i. All young of mouse M8 had maternally acquired antibodies to Sarcocystis neurona, but none developed clinical neurologic signs or had protozoal parasites in their tissues. All brains from mice that developed clinical signs contained merozoites that reacted positively to S. neurona antibodies using immunohistochemical techniques. Evidence from this study further supports the nine-banded armadillo being an intermediate host of S. neurona.

Striped skunks, initially negative for antibodies to Sarcocystis neurona, formed sarcocysts in skeletal muscles after inoculation with S. neurona sporocysts collected from a naturally infected Virginia opossum (Didelphis virginiana). Skunks developed antibodies to S. neurona by immunoblot and muscles containing sarcocysts were fed to laboratory-reared opossums which then shed sporulated Sarcocystis sporocysts in their faeces. Mean dimensions for sporocysts were 11.0 x 7.5 microm and each contained four sporozoites and a residuum. Sarcocysts from skunks and sporocysts from opossums fed infected skunk muscle were identified as S. neurona using PCR and DNA sequence analysis. A 2-month-old, S. neurona-naive pony foal was orally inoculated with 5 x 10(5) sporocysts. Commercial immunoblot for antibodies to S. neurona performed using CSF collected from the inoculated pony was low positive at 4 weeks p.i., positive at 6 weeks p.i., and strong positive at 8 weeks p.i. Gamma-interferon gene knockout mice inoculated with skunk/opossum derived sporocysts developed serum antibodies to S. neurona and clinical neurologic disease. Merozoites of S. neurona present in the lung, cerebrum, and cerebellum of mice were detected by immunohistochemistry using polyclonal antibodies to S. neurona. Based on the results of this study, the striped skunk is an intermediate host of S. neurona.

The nine-banded armadillo (Dasypus novemcinctus) is an intermediate host of at least three species of Sarcocystis, Sarcocystis dasypi, Sarcocystis diminuta, and an unidentified species; however, life cycles of these species have not been determined. Following feeding of armadillo muscles containing sarcocysts to the Virginia opossum (Didelphis virginiana), the opossums shed sporulated Sarcocystis sporocysts in their faeces. Mean dimensions for sporocysts were 11.0x7.5 microm and each contained four sporozoites and a residual body. Sporocysts were identified as Sarcocystis neurona using PCR and DNA sequencing. A 2-month-old foal that was negative for S. neurona antibodies in the CSF was orally inoculated with 5x10(5) sporocysts. At 4 weeks post-infection, the foal had a 'low positive' result by immunoblot for CSF antibodies to S. neurona and by week 6 had a 'strong positive' CSF result and developed an abnormal gait with proprioceptive deficits and ataxia in all four limbs. Based on the results of this study, the nine-banded armadillo is an intermediate host of S. neurona.

Gamma-interferon knockout mice have become the model animal used for studies on Sarcocystis neurona. In order to determine the viability of S. neurona sporocysts and to evaluate the course of the disease in these mice, sporocysts were collected from opossums (Didelphis virginiana), processed, and stored for varying periods of time. Gamma-interferon knockout mice were then inoculated orally with different isolates at different doses. These animals were observed daily for clinical signs until they died or it appeared necessary to humanely euthanize them. 15 of 17 (88%) mice died or showed clinical signs consistent with neurologic disease. The clinical neurologic symptoms observed in these mice appeared to be similar to those observed in horses. 15 of 17 (88%) mice were euthanized or dead by day 35 and organisms were observed in the brains of 13 of 17 (77%) mice. Dose appeared not to effect clinical signs, but did effect the amount of time in which the course of disease was completed with some isolates. The minimum effective dose in this study was 500 orally inoculated sporocysts. Efforts to titrate to smaller doses were not attempted. Direct correlation can be made between molecularly characterized S. neurona sporocysts and their ability to cause neurologic disease in gamma-interferon knockout mice.

The influence of the number of sporocysts in the inoculum of Sarcocystis falcatula on the morphology of the sarcocysts has not been reported in the literature. To determine if there is a relationship, different number of sporocysts were inoculated orally into wild-caught cowbirds. After 14 weeks, the cowbirds were euthanised and muscle tissue was examined grossly and by histologic sections. Sarcocysts were compared based on the numbers which developed and their sizes. There was a linear increase in the number of sarcocysts as the size of the inoculum increased, however, the size of the sarcocysts became smaller with the increase in number of sporocysts inoculated.

Equine protozoal myeloencephalitis is a common neurologic disease of horses in the Americas usually caused by Sarcocystis neurona. To date, the disease has not been induced in horses using characterized sporocysts from Didelphis virginiana, the definitive host. S. neurona sporocysts from 15 naturally infected opossums were fed to horses seronegative for antibodies against S. neurona. Eight horses were given 5x10(5) sporocysts daily for 7 days. Horses were examined for abnormal clinical signs, and blood and cerebrospinal fluid were harvested at intervals for 90 days after the first day of challenge and analyzed both qualitatively (western blot) and quantitatively (anti-17kDa) for anti-S. neurona IgG. Four of the challenged horses were given dexamethasone (0.1mg/kg orally once daily) for the duration of the experiment. All challenged horses immunoconverted against S. neurona in blood within 32 days of challenge and in CSF within 61 days. There was a trend (P = 0.057) for horses given dexamethasone to immunoconvert earlier than horses that were not immunosuppressed. Anti-17kDa was detected in the CSF of all challenged horses by day 61. This response was statistically greater at day 32 in horses given dexamethasone. Control horses remained seronegative throughout the period in which all challenged horses converted. One control horse immunoconverted in blood at day 75 and in CSF at day 89. Signs of neurologic disease were mild to equivocal in challenged horses. Horses given dexamethasone had more severe signs of limb weakness than did horses not given dexamethasone; however, we could not determine whether these signs were due to spinal cord disease or to effects of systemic illness. At necropsy, mild-moderate multifocal gliosis and neurophagia were found histologically in the spinal cords of 7/8 challenged horses. No organisms were seen either in routinely processed sections or by immunohistochemistry. Although neurologic disease comparable to naturally occurring equine protozoal myeloencephalitis (EPM) was not produced, we had clear evidence of an immune response to challenge both systemically and in the CNS. Broad immunosuppression with dexamethasone did not increase the severity of histologic changes in the CNS of challenged horses. Future work must focus on defining the factors that govern progression of inapparent S. neurona infection to EPM.

Five Virginia opossums (Didelphis virginiana) were fed muscles of brown-headed cowbirds (Molothrus ater) containing sarcocysts of Sarcocystis falcatula. Shedding of sporocysts was confirmed in all five opossums by fecal flotation. Counts were conducted daily for 2 weeks and then biweekly until the animals were euthanized and necropsied. The average prepatent period was 9.8 (7-16) days. The number of sporocysts shed varied greatly between the opossums with maximum mean shedding occurring at 71.6 (26-112) days post-infection (DPI). Average sporocyst production was 1480 sporocysts/gram of feces (SPG). Maximum output was 37,000 SPG. Average fecal yield in captivity was 17.5g of feces/day. Opossums shed 25,900 sporocysts/day (average) and a maximum of 647,500 sporocysts/day. All opossums shed sporocysts until time of euthanasia (46-200 DPI). Histologically, numerous sporocysts were present in the lamina propria at necropsy, primarily in the proximal half of the small intestine. Sporocysts were generally in clusters within the lamina propria of the luminal two-thirds of the villi. Sporocysts were found less frequently in the epithelium. No evidence of ongoing gametogony or other development was evident.

Quantitative hepatobiliary scintigraphy using 99mTc-mebrofenin was performed on eight normal cats and on the same cats after induction of experimental cholangiohepatitis by infection with the liver fluke Platynosomum concinnum. Hepatobiliary scintigraphy was performed 3 times at 10 weeks, 4 months and 6 months after infection. In addition, routine biochemical tests, hepatic ultrasound and ultrasound guided hepatic biopsy samples were obtained at the same time points, and the results compared with hepatobiliary scintigraphy. The normal hepatic extraction fraction was determined to be 85%, and the normal hepatic excretion half time (T 1/2) was 14 minutes. There was no significant change in scintigraphic parameters compared to pre-infection values at any time following infection with the liver fluke. No correlation between scintigraphic parameters and histologic scores was found; however, significant correlation was identified between parasite burden and histologic scores 6 months following infection. Despite the presence of severe multifocal histologic abnormalities, minimal clinical, biochemical and scintigraphic derangements were identified using this model of cholangiohepatitis. Based on this study, hepatobiliary scintigraphy appears to be an insensitive test for structural hepatobiliary abnormalities. The role of hepatobiliary scintigraphy in functional hepatobiliary abnormalities of the feline liver has not been determined.

The morphologic changes of subclinical Johne's disease in North American Bison (Bison bison) are characterized by microgranulomas composed of epithelioid macrophages and individual multinucleate giant cells of Langhans'-type occasionally containing individual cytoplasmic acid-fast bacilli compatible with Mycobacterium avium paratuberculosis. The microgranulomas are best visualized in the mesenteric lymph nodes of infected subclinical animals. Macrophages that can be confused with infection-associated epithelioid macrophages in the mesenteric lymph nodes are pigment-carrying cells from the intestinal tract. Mesenteric lymph node biopsy may be a useful diagnostic tool for detection of mild subclinical infection in individual ruminants from herds of unknown infection status. The biopsy may also be useful for Johne's disease surveillance during test-and-cull programs.

Gross and histopathologic examinations were performed on 70 North American bison (Bison bison) from a Mycobacterium avium paratuberculosis culture-positive herd. The bison examined were part of a breeding herd totaling 2,800 animals. Eight of 70 (11%) animals had gross findings of intestinal mucosal thickening, and 16 of 70 (23%) of the animals had enlarged mesenteric lymph nodes. Histologic lesions compatible with Johne's disease were diagnosed in 30 of 70 (43%) bison on the basis of the demonstration of noncaseating granulomatous inflammatory infiltrates and of one or more acid-fast bacilli characteristic of Mycobacterium avium paratuberculosis. A suspicious diagnosis of Johne's disease was obtained in 11 of 70 (16%) bison on the basis of the observation of noncaseating granulomatous inflammatory infiltrates without demonstrable acid-fast bacteria. Twenty-nine of 70 (41%) animals were assessed as histologically paratuberculosis free. Histologic results were compared to Johne's disease tests such as culture, serology, and polymerase chain reaction, which were performed on some of the cohort animals.

A 13-yr-old ring-tailed lemur (Lemur catta) was evaluated for depression, anorexia, polyuria, and polydipsia. The lemur was in poor body condition and was anemic, hypoalbuminemic, and hyponatremic. Cytologic examination of aspirates of the spleen, liver, and bone marrow and histopathologic examination of liver and bone marrow biopsies revealed a disseminated round cell tumor. After euthanasia, necropsy revealed hepatomegaly, splenomegaly, and mesenteric lymphadenomegaly. Neoplastic cells were present within the spleen, liver, kidneys, multiple lymph nodes, bone marrow, lung, small intestine, pancreas, and testicle and were composed of large anaplastic round cells in a background of small well-differentiated lymphocytes. Immunohistochemical analysis revealed that the small well-differentiated lymphocytes labeled for the anti-human T-cell marker, CD3, and the large anaplastic round cells labeled with the anti-human B-cell marker, CD79a. On the basis of the immunohistochemical staining results and morphologic appearance, a diagnosis of a T-cell-rich B-cell lymphoma was made.

Magnetic resonance images of the cranial abdomen were acquired from 15 clinically normal cats. All cats had T1-weighted images, 8 cats had T2-images made and 7 cats had T1-weighted post Gd-DTPA images acquired. Signal intensity measurements for T1, T2, and T1 post contrast sequences were calculated for liver, spleen, gallbladder, renal cortex, renal medulla, pancreas, epaxial muscles, and peritoneal fat. On T1-weighted images the epaxial muscle had the lowest signal intensity, followed by renal medulla, spleen, renal cortex, pancreas, liver and fat, respectively. On T2-weighted images, epaxial muscle had the lowest signal intensity followed by liver, spleen, fat, and gallbladder lumen. Calculations of specific organ percent enhancement following contrast medium administration were made and compared with that reported in humans. A brief review of the potential clinical uses of MR in cats is presented.

Eighty-three canine cutaneous mast cell tumors were graded histologically and evaluated immunohistochemically for p53 tumor-suppressor protein expression. An avidin-biotin immunohistochemical protocol incorporated a rabbit polyclonal antibody (CM-1) directed against normal and mutant p53 protein. Positive staining was observed in 44.6% (37/83) of tumors and included 50% (12/24) of grade I (well differentiated) tumors, 46.9% (23/49) of grade II (intermediate differentiation) tumors, and 20% (2/10) of grade III (poorly differentiated) tumors. A statistically significantly higher proportion (P < 0.019) of tumors from the head and neck (83.3%, 10/12), stained positive for p53 than tumors from the thorax, back, abdomen, and axilla (39.4%, 13/33), legs (35.7%, 10/28), or prepuce, scrotal, or inguinal areas (44.4%, 4/9). No statistically significant difference between p53 labeling and histologic grade, breed, or tumor size was present. Survival data were available for 53/83 (63.9%) of dogs. Positive reactivity for p53 was observed in 47% (25/53) of tumors within this group, with 57.9% (11/19) of grade I, 43.3% (13/30) of grade II, and 25% (1/4) of grade III tumors labeled. Mean survival time for the 53 dogs was 12.1 months. The median survival time for dogs with grade III tumors or tumors >5 cm was statistically significantly shorter (P < 0.0001) than for dogs with grades I and II or smaller tumors. Although p53 protein abnormalities may play a role in tumor development or behavior in some canine cutaneous mast cell tumors, immunoreactivity was not associated with lack of tumor differentiation, tumor locations previously shown to demonstrate aggressive biological behavior, breed predisposition, or survival times.

Feline herpesvirus-associated dermatitis has rarely been reported. Recently we documented a unique ulcerative and often persistent facial dermatitis or stomatitis syndrome associated with feline herpesvirus 1. We believe this syndrome is relatively common, with the 10 cases in our series diagnosed between 1996 and 1997. The syndrome is associated with epithelial cell necrosis, eosinophilic inflammation, and intraepithelial herpesvirus inclusion bodies. The prevalence of eosinophilic inflammation and low number of inclusion bodies may lead to the misdiagnosis of allergic dermatitis or a lesion within the eosinophilic granuloma complex group of disorders. Feline herpesvirus 1 can be identified in lesional tissue by PCR methodology. Most of our cases developed under circumstances suggesting reactivation of latent herpesvirus infection, and previous glucocorticoid therapy or stress from overcrowding may have played a role in lesion development. Cats with ulcerative dermatitis, especially of the face and nose, and cats with stomatitis should be evaluated for the presence of feline herpesvirus. Treatment options include surgical excision, topical or systemic antibiotic therapy to treat secondary bacterial infection, and oral alpha interferon.

Objective: To determine whether healthy dogs given high doses of methylprednisolone sodium succinate (MPSS) develop gastrointestinal tract ulcers and hemorrhage., Animals: 19 healthy male hound-type dogs., Procedure: Dogs were assigned randomly to intravenously receive high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, every 6 hours for a total of 48 hours; n = 10) or an equal volume of saline (0.9% NaCl) solution (9). Gastroduodenoscopy was performed before and after treatment. Endoscopic evidence of gross hemorrhage in the cardia, fundus, antrum, and duodenum of each dog was graded from none (0) to severe (3), and a total stomach score was calculated as the sum of the regional gastric scores. Number of ulcers were recorded. The pH of gastric fluid and evidence of occult gastric and fecal blood were measured. Food retention was recorded., Results: Gastric hemorrhage was evident in all dogs after MPSS administration and was severe in 9 of 10 dogs but not visible in any dog after saline treatment. Occult gastric blood was detected more commonly (9/10 vs 2/9), median gastric acidity was greater (pH 1 vs pH 3), and food was retained more commonly (7/10 vs 1/9) in the stomach of MPSS-treated dogs., Conclusions and Clinical Relevance: High doses of MPSS cause gastric hemorrhage in dogs. All dogs treated with high doses of MPSS should be treated with mucosal protectants or antacids to prevent gastric hemorrhage.

Objective: To determine whether administration of misoprostol prevents gastric hemorrhage in healthy dogs treated with high doses of methylprednisolone sodium succinate (MPSS)., Animals: 18 healthy hound-type dogs of both sexes., Procedure: All dogs were given high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, q 6 h for a total of 48 hours) IV. Dogs were assigned randomly to receive concurrent treatment with misoprostol (4 to 6 microg/kg, PO, q 8 h; n = 9) or an empty gelatin capsule (9). Gastroduodenoscopy was performed before and after treatment. Hemorrhage was graded from none (0) to severe (3) for each cardia, fundus, antrum, and duodenum. A total stomach score was calculated as the sum of the regional stomach scores. Food retention was recorded, and pH of gastric fluid was determined. Gastric and fecal occult blood was measured., Results: Gastric hemorrhage was evident in all dogs after MPSS administration, and its severity was similar in both groups. Median total stomach score was 6 for misoprostol-treated dogs and 5.5 for dogs given the gelatin capsule. Difference in gastric acidity, frequency of food retention, and incidence of occult blood in gastric fluid and feces was not apparent between the 2 groups., Conclusions and Clinical Relevance: Administration of misoprostol (4 to 6 microg/kg, PO, q 8 h) does not prevent gastric hemorrhage caused by high doses of MPSS. Alternative prophylactic treatment should be considered.

Malignant histiocytosis is a well-recognized canine tumour, occurring primarily in Bernese mountain dogs and characterized by disseminated histiocytic infiltration of multiple visceral organs. This report describes the light microscopical and ultrastructural features of a neoplasm composed of malignant histiocytes and confined to the brain. A poorly demarcated mass in the right parieto-occipital lobe of a miniature schnauzer was composed of loosely aggregated, pleomorphic cells with abundant eosinophilic cytoplasm, expanding the meninges. Many binucleated and multinucleated giant cells and mitotic figures were seen. Immunohistochemically, the tumour cells reacted intensely for lysozyme. Ultrastructurally, the neoplastic cells had features of histiocytic cells with abundant lysosomes. The findings in this case were strikingly similar to those of disseminated malignant histiocytosis described in other dog breeds., (Copyright 1999 W.B. Saunders Company Ltd.)

Objective: To determine scintigraphic, sonographic, and histologic changes associated with renal autotransplantation in cats., Animals: 7 adult specific-pathogen-free cats: 5 males, 2 females, 1 to 9 years old., Procedure: Renal autotransplantation was performed by moving a kidney (5 left, 2 right) to the left iliac fossa. Before and at multiple times after surgery, for a total of 28 days, cats were evaluated by B-mode and Doppler ultrasonography, scintigraphy, and renal biopsy., Results: By 24 hours after surgery, a significant decrease (42%) in mean glomerular filtration rate (GFR) and an increase in mean renal size (81% increase in cross-sectional area) were evident in the transplanted kidney, compared with preoperative values. By postsurgery day 28, reduction in GFR was 23%. Significant changes in renal blood flow velocity were identified in both kidneys. Consistent changes in resistive index or pulsatility index for either kidney could not be identified. When all postoperative histologic data were combined, the histologic score, indicating degree and numbers of abnormalities detected, for the transplanted kidney was significantly higher than that for the control kidney., Conclusions: Significant changes in renal function, size, and histologic abnormalities develop secondary to acute tubular necrosis in cats after uncomplicated renal autotransplantation., Clinical Relevance: Evaluation of renal size and function may be of benefit for clinical evaluation of feline renal transplant patients, whereas measurement of the resistive index may be of little clinical value.

Clinical, electromyographic, and pathologic findings characteristic of lead toxicosis were detected in a turkey vulture (Cathartes aura). The bird had generalized lower motor neuron dysfunction that progressed over 5 days. Electromyography revealed diffuse denervation potentials and a presumed decrement in the sciatic-tibial nerve conduction velocity. Histologic examination of peripheral nerves obtained at necropsy revealed changes that could be compatible with lead-induced neuropathy. Lead toxicosis was confirmed by determination of blood lead concentrations. Lead toxicosis causing neurologic disorders in birds has been described. However, this report emphasizes the effects of lead on the peripheral nervous system and demonstrates the use of electromyography for diagnosis of peripheral neuropathy in birds.

Equine protozoal myeloencephalitis (EPM) is a debilitating neurologic disease of the horse. The causative agent. Sarcocystis neurona, has been suggested to be synonymous with Sarcocystis falcatula, implying a role for birds as intermediate hosts. To test this hypothesis, opossums (Didelphis virginiana) were fed muscles containing S. falcatula sarcocysts from naturally infected brown-headed cowbirds (Molothrus ater). Ten horses were tested extensively to ensure no previous exposure to S. neurona and were quarantined for 14 days, and then 5 of the horses were each administered 10(6) S. falcatula sporocysts collected from laboratory opossums. Over a 12-wk period, 4 challenged horses remained clinically normal and all tests for S. neurona antibody and DNA in serum and cerebrospinal fluid were negative. Rechallenge of the 4 seronegative horses had identical results. Although 1 horse developed EPM, presence of S. neurona antibody prior to challenge strongly indicated that infection occurred before sporocyst administration. Viability of sporocysts was confirmed by observing excystation in equine bile in vitro and by successful infection of naive brown-headed cowbirds. These data suggest that S. falcatula and S. neurona are not synonymous. One defining distinction is the apparent inability of S. falcatula to infect horses, in contrast to S. neurona, which was named when cultured from equine spinal cord.

The normal sonographic appearance of the stomach in various degrees of distension, the duodenum, the small intestine, and the large intestine was determined in awake and sedated cats. The mean stomach rugal fold thickness was 4.38 mm, and the interrugal thickness was 2.03 mm. No significant difference in stomach wall thickness was seen when the stomach was empty, half full, or full. The duodenal wall thickness was significantly greater than other parts of the small intestine, and this difference was accentuated by sedation (awake mean 2.4 mm; sedated mean 2.71 mm). The mean small intestinal wall thickness was 2.1 mm, and the mean colonic wall thickness was 1.67 mm. The five characteristic sonographic layers similar to that seen in the gastrointestinal tract of other species were routinely identified at all regions of the feline gastrointestinal tract.

A 9-year-old rabbit was evaluated for a mass on the right elbow. As a result of preoperative radiography, another mass was identified in the cranial portion of the mediastinum. Ultrasound guided fine needle aspiration was used for cytologic evaluation of the mass in the mediastinum and resulted in a presumptive diagnosis of thymoma. A median sternotomy approach was chosen to allow wide exposure for meticulous dissection in the cranial portion of the thoracic region. Histologic examination and immunoperoxidase labeling of lymphocytes with CD3 (a T cell marker) confirmed the diagnosis. The mass on the right elbow was subsequently removed and identified as a neurofibrosarcoma. Multiple appendicular masses that developed at separate locations and distinct times were excised and classified as locally invasive primary neurofibrosarcomas. Postmortem examination 9 months after initial evaluation confirmed recurrence of the neurofibrosarcoma at previous surgical sites. Gross or histologic evidence of thymoma was not evident. Prognosis is dismal for incompletely excised soft tissue sarcomas, because they are locally invasive and often recur.

Objective: To evaluate clinical and histologic effects of surgically created urethral intussusception and determine whether it creates a high-pressure zone that resists passive urine flow in clinically normal dogs., Animals: 8 healthy adult sexually intact female dogs., Procedure: Urethral pressure profilometry was used to measure maximal urethral closure pressure (MUCP) and functional profile length (FPL) in dogs sedated with xylazine hydrochloride and atropine before and 2, 4, 7, 14, 28, 60, and 90 days after surgery. Cystourethral leak point pressure (CLPP) and cystourethral leak point volume (CLPV) were determined in anesthetized dogs immediately before and after surgery. Dogs were assigned to 4 groups of 2 dogs each; groups were euthanatized 4, 14, 28, and 90 days later, and representative tissues were examined., Results: Dog 1 developed complete postoperative urethral obstruction. The procedure was altered, and all dogs recovered without complication. Mild inflammation attributable to surgical manipulation, but not ischemic damage or reduction of the intussusception, was evident. Comparison of preoperative MUCP and FPL with postoperative values did not yield significant differences. Immediate postoperative CLPP and CLPV were significantly higher than preoperative values, but were not significantly increased at euthanasia. A distinct but nonsignificant pressure spike was observed in postoperative urethral pressure profiles and persisted in 7 of 8 dogs., Conclusions: Urethral intussusception does not have deleterious effects when performed as described. Urodynamic data do not support the premise that urethral intussusception will create a high-pressure zone in the urethra that will resist passive urine flow long term in clinically normal dogs.

The prostate gland of 11 normal dogs and five dogs with histologically confirmed chronic lymphocytic or lymphoplasmocytic prostatitis were imaged with grey-scale and Doppler ultrasound. Three vessel types (prostatic artery, capsular artery and parenchymal artery) were identified with color Doppler and the resistive index and maximum and minimum velocities were measured with pulsed wave Doppler. No differences between normal dogs and dogs with prostatitis was identified in either grey-scale ultrasound or in any Doppler parameters measured. Regardless of histologic diagnosis, acepromazine (0.05 mg/kg i.v.) caused a significant decrease in capsular artery maximum and minimum velocities and prostatic artery resistive index. This study establishes normal Doppler ultrasound parameters for the intact male canine prostate gland. Additional studies are necessary to further evaluate the clinical utility of Doppler ultrasound in canine prostatic diseases.

A 9-year-old Arabian mare was admitted for evaluation of multiple subcutaneous nodules and infertility. Fine-needle aspiration of one of the subcutaneous nodules resulted in a cytologic diagnosis of histiolymphocytic lymphoma. Palpation per rectum and transrectal ultrasonography revealed a mass associated with the left ovary. Excision of the ovarian tumor was performed, and a histopathologic diagnosis of granulosa-theca cell tumor was made. After removal of the granulosa-theca cell tumor, subcutaneous nodules regressed. The referring veterinarian reported that the nodules had also disappeared and then recurred after administration of a synthetic progestin. To further characterize the lymphoma and investigate this possible hormonal relationship, immunophenotyping and estrogen and progesterone receptor assays were performed. The subcutaneous lymphoma was classified as a T-cell rich B-cell lymphoma, results of estrogen receptor assays were negative, and results of progesterone receptor assays were positive. Clinical observations of subcutaneous lymphoma in horses indicate that the waxing and waning nature of these tumors may be associated with the estrous cycle, pregnancy, foaling, and lactation. Clinical observations and identification of progesterone receptors suggest that a relationship between serum steroid hormone concentrations, such as estrogen and progesterone, and subcutaneous lymphoma may exists.

Motor neuron diseases of domestic animals have rarely been described. Three cats with adult-onset, chronic, progressive generalized muscle weakness characterized initially by trembling on exertion and later by extreme difficulty in walking, cervical ventroflexion, dysphagia, and marked muscle atrophy were elevated. Spinal reflexes were evident early but were nondetectable as the disease progressed. Electromyography revealed fibrillation potentials, with nerve conduction velocities within the reference range. Histologic examination of muscle specimens revealed denervation. Marked neuron loss and gliosis were detected in the ventral horns of the spinal cord, with atrophy of ventral nerve rootlets. Less dramatic neuron loss was seen in brain stem motor nuclei. Electron microscopic examination of the ventral horns disclosed hypertrophied astrocytes, with densely arrayed intermediate filaments, swollen axons with large filamentous accumulations, and many macrophages with lipofuscin-like inclusions. Clinical and pathologic findings were consistent with a progressive neurodegenerative disease affecting spinal and some bulbar motor nuclei.

Eighty canine epithelial colorectal tumors obtained by excisional biopsy were evaluated immunohistochemically for p53 tumor suppressor gene protein. Dogs in the study average 6.9 years of age (range, 1-12.5 years). A standard avidin-biotin immunohistochemical protocol incorporated a polyclonal antibody of rabbit origin (CM-1) as the primary antibody. Positive staining was observed within all subcategories of lesions, including hyperplastic polyps 1/2 (50%), adenomas 14/29 (48%), carcinomas in situ 9/22 (41%), adenocarcinomas 3/4 (75%), and invasive carcinomas 8/23 (35%). A total of 35/80 (44%) positive tumors wee identified. Fifteen of 31 (48%) benign tumors labeled for p53 protein compared to 20/49 (41%) malignant tumors. Survival data was available for 57/80 (71%) dogs. The average age of dogs within the group with survival data was 4.4 years. Males predominated 34/57 (60%). Mean survival time was 20.6 months. There was no significant difference in survival time between dogs grouped according to p53 immunoreactivity, cellular stain location, or tumor site. A statistically significant increase in survival time was observed between dogs with clean surgical margins and those without (P < 0.018) and for dogs with adenomas or carcinomas in situ over dogs with invasive carcinomas (P < 0.02). In this study, the overall greater positive staining frequency of benign lesions compared to malignant lesions is contrary to data derived from similar immunohistochemical analyses of human tumors and is incongruous with the theorized late-stage participation of the p53 protein in the development of human colorectal cancers. The results of this study suggest that if the p53 tumor suppressor gene protein is involved in the progression of canine colorectal tumors, it may play a relatively early role, possibly analogous to the early appearance of p53 overexpression in precancerous lesions of human ulcerative colitis. Immunohistochemical detection of p53 was not useful prognostically.

Sections from 35 formalin-fixed, paraffin-embedded, canine gastrointestinal stromal tumors consisting of 14 leiomyomas (five stomach, three small intestine, two colon, four rectum), 18 leiomyosarcomas (one stomach, five small intestine, nine cecum, three rectum), two undifferentiated sarcomas (two stomach), and one neurofibrosarcoma (small intestine) were examined for the expression of vimentin, S-100 protein, alpha-smooth muscle actin, and desmin via immunoperoxidase methodology using an avidin-biotin complex technique. The leiomyomas were 4/14 (29%) vimentin-positive, 3/14 (21%) S-100 protein-positive, 10/14 (71%) alpha-smooth muscle actin-positive and 13/14 (93%) desmin-positive. Leiomyosarcomas were 18/18 (100%) vimentin-positive, 11/18 (61%) S-100 protein-positive, 9/18 (50%) a-smooth muscle actin-positive, and 15/18 (83%) desmin-positive. The undifferentiated sarcomas were 2/2 (100%) vimentin-positive, 2/2 (100%) S-100 protein-positive, 1/2 (50%) alpha-smooth muscle actin-positive, and 0/2 (0%) desmin-positive. The neurofibrosarcoma was vimentin and S-100 protein-positive and alpha-smooth muscle actin- and desmin-negative. Thirty-one of thirty-five (89%) of all neoplasms demonstrated reactivity for either desmin and/or alpha-smooth muscle actin. S-100 protein reactivity occurred in 17/35 (49%) of all specimens. Lack of desmin and alpha-smooth muscle actin reactivity occurred in 4/35 (11%) of all specimens, all of which were vimentin-positive. The immunohistochemical results indicate that the majority of canine gastrointestinal stromal tumors (GIST) with light microscopic features of smooth muscle cells have immunohistochemical staining patterns supporting smooth muscle differentiation. Vimentin reactivity correlated with a light microscopic diagnosis of malignancy. The lack of smooth muscle cell markers in some tumors and the high percentage of cases positive for S-100 protein may suggest a more complex histogenesis or differentiation for subgroups of these tumors.

Physical examination of an adult female white-faced saki (Pithecia pithecia) revealed midabdominal multiple cystic structures. The animal developed a grade 3/4 reaction to old mammalian tuberculin injected into the right eyelid. Significant clinicopathologic findings included marked hyperproteinemia (9.2 g/dl), hyperglobulinemia (6.1 g/dl), and hypoalbuminemia (3.1 g/dl). Ultrasonography revealed multiple abdominal masses of varying echogenicity. The animal was euthanized and necropsied. Significant histopathologic findings included multifocal lymphadenitis with cystic degeneration of multiple visceral lymph nodes. Mycobacterium avium-intracellulare was cultured from a mesenteric lymph node.

Objective: To determine the effects of 3 sedative protocols (butorphanol and diazepam [BD] IV; acepromazine and butorphanol [AB] IV; diazepam and ketamine [DK] IV) on glomerular filtration rate (GFR) as measured by 99mTc DTPA nuclear scintigraphy and to compare them with GFR measured without sedation. Cardiovascular, respiratory, and sedative effects of each protocol also were measured., Animals: 12 adult male Walker Hounds., Procedure: Systolic, diastolic, and mean arterial blood pressures and heart and respiratory rates were measured before, during, and after scintigraphic measurement of GFR., Results: Difference in GFR was not significant between any of the sedative regimens and the control. The DK protocol caused significant increases in systolic, diastolic, and mean arterial blood pressure; compared with the AB and BD protocols, it caused significant increases in heart rate versus all protocols, and was associated with the lowest mean GFR (2.80 ml/min/kg of body weight). The AB protocol caused significant decreases in systolic, diastolic, and mean arterial blood pressures, compared with DK and the nonsedation protocols. Mean GFR for the BD protocol was 2.94 ml/min/kg, and was 3.13 ml/min/kg for the AB and the nonsedation protocols. The AB protocol provided the best sedation with minimal additional restraint required. The BD and nonsedation protocols often were associated with substantial dog movement. The DK protocol induced inadequate duration of immobilization (< 10 minutes) in some dogs and excitement in others., Conclusion: GFR measurements obtained with any of the sedative protocols were not significantly different, compared with measurements in awake dogs. The AB protocol provides the best sedative effects and was associated with GFR values identical to those in awake dogs. Systemic hypotension caused by acepromazine did not decrease GFR in clinically normal dogs.