Novel patch biomaterial treatment for colon diverticulosis in swine model.

Current leading managements for diverticular disease cannot prevent the recurrence of diverticulitis, bleeding and/or other complications. There is an immediate need for developing new minimal invasive therapeutic strategies to prevent and treat this disease. Through a biomechanical analysis of porcine colon with diverticular lesions, we proposed a novel adhesive patch concept aiming at mechanical reconstruction of the diseased colon wall. This study aims to evaluate the surgical feasibility (safety and efficacy) of pulmonary visceral pleura (PVP) patch therapy using a pig model of diverticulosis. Six female Yucatan miniature pigs underwent collagenase injection (CI) for the development of diverticular lesions. The lesions in each animal either received patch implantation (treated group, n = 40 for 6 pigs) or left intact (untreated group, n = 44 for 6 pigs). The normal colonic wall in each animal received patch implantation at two spots to serve as control (n = 12 for 6 pigs). After 3 months of observation, the performance and safety of the patch treatment were evaluated through macroscopic and histological examination. We found that 95% of pouch-like herniation of the mucosa was prevented from the colon wall with the treatment. The pouch diameter was significantly reduced in the treated group as compared to the untreated group (p < 0.001). The patch application caused a significant increase in the levels of collagen of the colon tissue as compared to the untreated and control groups (p < 0.001). No difference was found in the lymphocyte and macrophage inflammatory infiltrate between the groups. Our results suggest that patch treatment efficiently inhibits the diverticular pouch deformation and promotes the healing of the colon wall with a normal inflammatory response, which may minimize the risk of diverticulosis reoccurrence and complications over time.

Comparison of Fibered versus Nonfibered Coils for Venous Embolization in an Ovine Model.

PURPOSE: To compare nylon fibered (F) with nonfibered (NF) coils for embolization in an ovine venous model. MATERIALS AND METHODS: Four- to 8-mm-diameter, 0.035-inch F and NF coils were deployed in 24 veins in 6 sheep. The number of coils, total length of the coils, and length of implanted coil pack required to achieve complete stasis were recorded, as were vessel diameter, radiation dose, ease of packing, damage to embolized vessel, and time to stasis. Venography at 1 and 3 months was used to assess the migration and durability of vessel occlusion. Veins were harvested at 3 months. RESULTS: F and NF coils were deployed in 24 veins, and stasis was achieved, without immediate coil migration or vessel damage. The mean numbers of F and NF coils per vein were 5 and 8.75, respectively (P = .007). The vessel diameter between the groups was not statistically different. The total coil length (F, 70 cm vs NF, 122.5 cm; P = .0007), coil pack length (F, 29.3 mm vs NF, 39.4 mm; P = .003), time to stasis (F, 5.3 minutes vs NF, 9.0 minutes; P = .008), and radiation dose (F, 25.3 mGy vs NF, 34.9 mGy; P = .037) were significantly different between the groups. Challenges with the animal model prevented conclusive long-term results. Migration occurred with 8 of 11 (72%) coil packs in the femoral veins and 0 of 13 (0%) coil packs in the internal iliac and deep femoral veins. Venography demonstrated that of 16 remaining coil packs, 11 were occluded at 1 month and 10 remained occluded at 3 months. CONCLUSIONS: Fibers allow for significantly fewer coils to achieve immediate venous occlusion.

The cytologic and histologic diagnosis of ureteral fibroepithelial polyp in a dog.

A 6-year-old, intact male, brindled, 30-Lb English Bulldog presented to the Purdue University Veterinary Teaching Hospital with a recurrent history of hematuria, periuria, and lethargy that responded temporarily to antibiotic therapy. The work-up included a complete blood count, serum biochemical profile, complete urinalysis, diagnostic imaging (abdominal radiographs and ultrasound with contrast urography), and exploratory laparotomy. The diagnostic imaging findings and subsequent exploratory revealed a unilateral, intraluminal, right-sided, 3-cm ureteral mass extending from the proximal ureter into the renal pelvis. Subsequently, a unilateral right-sided ureteronephrectomy followed by biopsy with cytopathology/cytology (impression smears) and histopathology of the ureteral mass was performed. The cytopathologic interpretation was benign mesenchymal proliferation with mildly atypical urothelial cells. The association of this mass with vascular tissue and a benign nuclear appearance on cytology is similar to reports of fibroepithelial polyps (FEPs) and myxomatous tumors. Histopathology diagnosed the mass as an FEP. Cytopathology proved useful in the presumptive diagnosis of this benign urothelial polyp. To the authors' knowledge, this is the first report using cytopathology to depict and characterize FEPs in veterinary and human medical literature.

Novel swine model of colonic diverticulosis.

The pathophysiology of colonic diverticulosis has not been completely understood. The development of appropriate animal models is essential to study diverticular disease. To date, no large animal models are available for this disease condition. The objective of this study was to develop a swine model by damaging the colon wall, combined with or without a low-fiber diet to mimic the pathogenesis of diverticulosis. To create a weakness on the colon wall, collagenase was applied in vivo to degrade the collagen in the colon wall. Three groups of Yucatan minipigs were included. Group 1 (n = 12) underwent collagenase injection (CI) with a low-fiber diet for 6 mo, group 2 (n = 8) underwent CI alone with a standard swine diet for 6 mo, and group 3 (n = 12) received a low-fiber diet alone for 6 mo. We found that diverticulosis occurred in 91.7% (11 of 12) of pigs in the CI + diet group and 100% (8 of 8) in CI-alone group. Moreover, around 30-75% of colon CI spots for each pig developed diverticular lesions. Diet alone for 6 mo did not induce diverticulosis. The endoscopic and histological examinations revealed the formation of multiple wide-mouthed diverticular lesions along the descending colon. Our results provide convincing evidence of the high efficacy of the reduced colon wall strength caused by CI in the development of a swine model of diverticulosis. Low-fiber diet consumption for 6 mo had no influence on the generation time or incidence rate of diverticulosis. In this model, digestion of the collagen in the colonic wall is sufficient to cause diverticulosis. NEW & NOTEWORTHY Effective large animal models of diverticulosis are currently lacking for the study of diverticular disease. This study marks the first time that a swine model of diverticulosis was developed by damaging colon wall structure, combined with or without a low-fiber diet. We found that a defect of colon wall could result in colon diverticular lesions within 6 mo in swine. This animal model mimicking the pathological process of diverticulosis is of great clinical value.

Effect of High-Calcium Diet on Coronary Artery Disease in Ossabaw Miniature Swine With Metabolic Syndrome.

BACKGROUND: Calcium is a shortfall essential nutrient that has been a mainstay of osteoporosis management. Recent and limited findings have prompted concern about the contribution of calcium supplementation to cardiovascular risk. A proposed mechanism is through the acceleration of coronary artery calcification. Determining causality between calcium intake and coronary artery calcification has been hindered by a lack of sensitive methodology to monitor early vascular calcium accumulation. The primary study aim was to assess the impact of high calcium intake on coronary artery calcification using innovative calcium tracer kinetic modeling in Ossabaw swine with diet-induced metabolic syndrome. Secondary end points (in vitro wire myography, histopathology, intravascular ultrasound) assessed coronary disease. METHODS AND RESULTS: Pigs (n=24; aged ≈15 months) were fed an atherogenic diet with adequate calcium (0.33% by weight) or high calcium (1.90% from calcium carbonate or dairy) for 6 months. Following 5 months of feeding, all pigs were dosed intravenously with (41)Ca, a rare isotope that can be measured in serum and tissues at a sensitivity of 10(-18) mol/L by accelerator mass spectrometry. Kinetic modeling evaluated early coronary artery calcification using (41)Ca values measured in serial blood samples (collected over 27 days) and coronary artery samples obtained at sacrifice. Serum disappearance of (41)Ca and total coronary artery (41)Ca accumulation did not differ among groups. Secondary end points demonstrated no treatment differences in coronary artery disease or function. CONCLUSION: There was no detectable effect of high calcium diets (from dairy or calcium carbonate) on coronary artery calcium deposition in metabolic syndrome swine.

Early postnatal respiratory viral infection induces structural and neurochemical changes in the neonatal piglet brain.

Infections that cause inflammation during the postnatal period are common, yet little is known about their impact on brain development in gyrencephalic species. To address this issue, we investigated brain development in domestic piglets which have brain growth and morphology similar to human infants, after experimentally infecting them with porcine reproductive and respiratory syndrome virus (PRRSV) to induce an interstitial pneumonia Piglets were inoculated with PRRSV on postnatal day (PD) 7 and magnetic resonance imaging (MRI) was used to assess brain macrostructure (voxel-based morphometry), microstructure (diffusion tensor imaging) and neurochemistry (MR-spectroscopy) at PD 29 or 30. PRRSV piglets exhibited signs of infection throughout the post-inoculation period and had elevated plasma levels of TNFα at the end of the study. PRRSV infection increased the volume of several components of the ventricular system including the cerebral aqueduct, fourth ventricle, and the lateral ventricles. Group comparisons between control and PRRSV piglets defined 8 areas where PRRSV piglets had less gray matter volume; 5 areas where PRRSV piglets had less white matter volume; and 4 relatively small areas where PRRSV piglets had more white matter. Of particular interest was a bilateral reduction in gray and white matter in the primary visual cortex. PRRSV piglets tended to have reduced fractional anisotropy in the corpus callosum. Additionally, N-acetylaspartate, creatine, and myo-inositol were decreased in the hippocampus of PRRSV piglets suggesting disrupted neuronal and glial health and energy imbalances. These findings show in a gyrencephalic species that early-life infection can affect brain growth and development.

Early postnatal respiratory viral infection alters hippocampal neurogenesis, cell fate, and neuron morphology in the neonatal piglet.

Respiratory viral infections are common during the neonatal period in humans, but little is known about how early-life infection impacts brain development. The current study used a neonatal piglet model as piglets have a gyrencephalic brain with growth and development similar to human infants. Piglets were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) to evaluate how chronic neuroinflammation affects hippocampal neurogenesis and neuron morphology. Piglets in the neurogenesis study received one bromodeoxyuridine injection on postnatal day (PD) 7 and then were inoculated with PRRSV. Piglets were sacrificed at PD 28 and the number of BrdU+ cells and cell fate were quantified in the dentate gyrus. PRRSV piglets showed a 24% reduction in the number of newly divided cells forming neurons. Approximately 15% of newly divided cells formed microglia, but this was not affected by sex or PRRSV. Additionally, there was a sexual dimorphism of new cell survival in the dentate gyrus where males had more cells than females, and PRRSV infection caused a decreased survival in males only. Golgi impregnation was used to characterize dentate granule cell morphology. Sholl analysis revealed that PRRSV caused a change in inner granule cell morphology where the first branch point was extended further from the cell body. Males had more complex dendritic arbors than females in the outer granule cell layer, but this was not affected by PRRSV. There were no changes to dendritic spine density or morphology distribution. These findings suggest that early-life viral infection can impact brain development.

Respiratory viral infection in neonatal piglets causes marked microglia activation in the hippocampus and deficits in spatial learning.

Environmental insults during sensitive periods can affect hippocampal development and function, but little is known about peripheral infection, especially in humans and other animals whose brain is gyrencephalic and experiences major perinatal growth. Using a piglet model, the present study showed that inoculation on postnatal day 7 with the porcine reproductive and respiratory syndrome virus (PRRSV) caused microglial activation within the hippocampus with 82% and 43% of isolated microglia being MHC II(+) 13 and 20 d after inoculation, respectively. In control piglets, <5% of microglia isolated from the hippocampus were MHC II(+). PRRSV piglets were febrile (p < 0.0001), anorectic (p < 0.0001), and weighed less at the end of the study (p = 0.002) compared with control piglets. Increased inflammatory gene expression (e.g., IL-1ß, IL-6, TNF-α, and IFN-γ) was seen across multiple brain regions, including the hippocampus, whereas reductions in CD200, NGF, and MBP were evident. In a test of spatial learning, PRRSV piglets took longer to acquire the task, had a longer latency to choice, and had a higher total distance moved. Overall, these data demonstrate that viral respiratory infection is associated with a marked increase in activated microglia in the hippocampus, neuroinflammation, and impaired performance in a spatial cognitive task. As respiratory infections are common in human neonates and infants, approaches to regulate microglial cell activity are likely to be important.

Gene expression differences during the heterogeneous progression of peripheral atherosclerosis in familial hypercholesterolemic swine.

BACKGROUND: The heterogeneous progression of atherosclerotic disease in the peripheral arteries is currently not well understood. In humans, artery specific disease progression is partly attributed to the local hemodynamic environments. However, despite similar hemodynamic environments, porcine brachial arteries are protected while femoral arteries are highly susceptible to advanced lesion formation. The aim of this investigation was to determine whether artery specific gene expression patterns contribute to the uneven distribution of peripheral arterial disease (PAD) in Rapacz Familial-Hypercholesterolemic (FHC) swine. RESULTS: Histological results confirmed rapid atherosclerotic disease progression in femoral but not brachial arteries. A total of 18,922 probe sets had sufficient signal abundance. A main effect for age and artery was observed for 1784 and 1256 probe sets, respectively. A significant age x artery interaction was found for 184 probe sets. Furthermore, comparison between arteries found a decrease from 714 to 370 differentially expressed transcripts from nine months to two years of age. Gene ontology analysis of the 56 genes with a main effect for artery and an age x artery interaction identified vascular smooth muscle contraction as enhanced biological signaling pathway. CONCLUSION: This is the first investigation to report that the total number of differential genes decreases with diverging atherosclerotic disease pattern between porcine brachial and femoral arteries.

Double BioDisk: a new bioprosthetic device for transcatheter closure of atrial septal defects - a feasibility study in adult sheep.

BACKGROUND: To evaluate the long-term effectiveness and safety of a new Double BioDisk (DBD) device for closure of atrial septal defect (ASD). MATERIALS AND METHODS.: ASD was created with transeptal needle (TS) followed by balloon dilatation in 12 sheep weighing 40.1 to 64 kg (mean 55.2 ± 7.1). The ASD diameters were measured after creation and two weeks later before DBD implantation. The DBDs consists of two nitinol rings 18 to 28 mm in diameter connected with small cannulas and covered with a porcine small intestinal submucosa (SIS). They were implanted via a 10 Fr sheath. DBD effectiveness was evaluated by angiocardiography and by intra-cardiac echogram (ICE) with Doppler studies. Two animals were acute, two were followed for 6 weeks, three for 3 months, three for 6 months and two for 12 months. RESULTS: TS punctures were successful in 10 sheep. In two sheep ASD was created by existing PFO dilation. The ASD size ranged from 13-15 mm (mean 14.1± 0.73 mm) after initial balloon dilation and from 9-13 mm (mean 10.06 ± 1.37 mm) after two weeks. In all animals none of the successfully implanted DBDs spontaneously embolized on release or on follow up. ICE demonstrated no shunting around the DBDs during follows ups. Macroscopic and histologic evaluation of the 6, 12, 24 and 52 weeks animals showed that DBDs were well incorporated in the atrial septum with complete shunt closure. The SIS showed progressive remodeling with the host cells, including endothelization of the DBD devices. CONCLUSIONS: ASD closure with the Double BioDisk is safe and effective in adult sheep.

Dual infection with Pythium insidiosum and Blastomyces dermatitidis in a dog.

A 4-year-old male neutered Labrador Retriever with severe gastrointestinal signs, but no respiratory signs, was diagnosed with multifocal pyogranulomatous gastritis, enteritis, and lymphadenitis with intralesional hyphae and multifocal pyogranulomatous pneumonia with intralesional yeast. Based on cytologic evaluation, histologic examination with special stains, and immunohistochemical analysis of tissues collected antemortem or at necropsy, dual infections with Pythium insidiosum and Blastomyces dermatitidis were detected and are reported for the first time.

Zwitterionic chitosan derivative, a new biocompatible pharmaceutical excipient, prevents endotoxin-mediated cytokine release.

Chitosan is a cationic polymer of natural origin and has been widely explored as a pharmaceutical excipient for a broad range of biomedical applications. While generally considered safe and biocompatible, chitosan has the ability to induce inflammatory reactions, which varies with the physical and chemical properties. We hypothesized that the previously reported zwitterionic chitosan (ZWC) derivative had relatively low pro-inflammatory potential because of the aqueous solubility and reduced amine content. To test this, we compared various chitosans with different aqueous solubilities or primary amine contents with respect to the intraperitoneal (i.p.) biocompatibility and the propensity to induce pro-inflammatory cytokine production from macrophages. ZWC was relatively well tolerated in ICR mice after i.p. administration and had no pro-inflammatory effect on naïve macrophages. Comparison with other chitosans indicates that these properties are mainly due to the aqueous solubility at neutral pH and relatively low molecular weight of ZWC. Interestingly, ZWC had a unique ability to suppress cytokine/chemokine production in macrophages challenged with lipopolysaccharide (LPS). This effect is likely due to the strong affinity of ZWC to LPS, which inactivates the pro-inflammatory function of LPS, and appears to be related to the reduced amine content. Our finding warrants further investigation of ZWC as a functional biomaterial.

Gene expression differences in healthy brachial and femoral arteries of Rapacz familial hypercholesterolemic swine.

The mechanisms underlying the unequal distribution of atherosclerotic disease in the peripheral arteries are currently unclear. Gene expression differences in healthy arteries may influence the heterogeneous distribution of atherosclerosis. Therefore, this investigation compares gene expression in healthy atheroprotected brachial and atherosusceptible femoral arteries of young and disease free Rapacz familial hypercholesterolemic (FHC) swine. We hypothesized that transcripts related to atherosusceptibility would be differentially expressed between these arteries prior to the onset of disease. Femoral and brachial arteries were harvested from four 13-day-old Rapacz FHC swine. No atherosclerotic disease was detected using Sudan IV, Verhoeff-van Gieson, and hematoxylin-eosin staining. Gene expression was quantified using Affymetrix GeneChip Porcine Genome Arrays. An average of 15,552 probe sets had detectable transcripts, while 430 probe sets showed a significant differential expression between arteries (false discovery rate < 0.05). The human orthologs of 63 probe sets with differential expression and a 1.5-fold or greater transcript abundance between arteries are associated with Wnt/ß-catenin, lysophospholipid, and Ca-signaling, as well as apoptosis. This is the first investigation reporting that differences in relative abundance of gene expression exist between brachial and femoral arteries in young Rapacz FHC swine prior to the development of atherosclerotic lesions.

Polymer-free paclitaxel-coated Zilver PTX Stents--evaluation of pharmacokinetics and comparative safety in porcine arteries.

PURPOSE: To evaluate the pharmacokinetics and safety of the Zilver PTX Drug-Eluting Stent (Cook Medical, Bloomington, Indiana) in a normal porcine artery model. MATERIALS AND METHODS: Pharmacokinetic analyses were performed using 18 pigs, each implanted with four paclitaxel-coated stents. Paclitaxel remaining on the stents, delivered locally (to artery wall), regionally (to adjacent and downstream muscle), and systemically (to plasma), was determined at various times through 56 days. For safety evaluation, local, regional, and systemic responses were grossly and histologically assessed at 1 month, 3 months, and 6 months in 21 additional pigs and compared with the responses to bare metal stents in 21 separate pigs. RESULTS: Stents delivered approximately 95% of the total paclitaxel within 24 hours after deployment. Nonetheless, there were sustained paclitaxel levels in the artery wall through 56 days, maintained at approximately 20% of the peak level through 14 days. Very little paclitaxel was distributed regionally or systemically, becoming undetectable in plasma at 10 hours. Complete necropsy, hematology, and serum chemistry revealed no adverse effects associated with the paclitaxel-coated stents. Within 3 months, vessels with both paclitaxel-coated and bare metal stents showed comparable, complete healing. CONCLUSIONS: The Zilver PTX stent appears to be safe, achieves sustained paclitaxel levels in the artery wall, and shows complete vessel healing comparable to bare metal stents within 3 months.

Retained fetal membranes in C57BL/6NCrl mice: description of clinical case presentations and related epidemiologic findings.

During a triinstitutional study to test whether individually ventilated caging systems impaired welfare and reproduction relative to static housing systems, varying numbers (2 to 7) of discoid-shaped, fleshy structures were found in utero of 17 postpartum female mice on study. Further investigation revealed these structures to be retained fetal membranes (RFM). A point prevalence of 24.3% was calculated based on a total population of 70 postpartum female mice on study. This finding was preceded by 3 typical clinical presentations, which are described here. We designed a case-control matched cross-sectional epidemiologic study to identify associated risk factors and antemortem indicators of RFM. Housing on the bottom shelves and attachment to the rack systems were factors associated with a diagnosis of the condition. In addition, neutrophilia, monocytosis, lymphopenia, and decreasing hematocrit values were associated with the diagnosis of RFM. These results confirmed that a CBC can be a useful antemortem screening test for the identification of affected mice. We conclude that RFM are likely an incidental finding although they may present concurrent with other pregnancy complications.

Zwitterionic chitosan derivatives for pH-sensitive stealth coating.

Zwitterionic chitosan, a chitosan derivative with a unique pH-dependent charge profile, was employed to create a stealth coating on the cationic surface of drug carriers. Zwitterionic chitosans were synthesized by amidation of chitosan with succinic anhydride. The succinic anhydride-conjugated chitosan had an isoelectric point, which could be easily tuned from pH 4.9 to 7.1 and showed opposite charges below and above the isoelectric point. The succinic anhydride-conjugated chitosan was able to inhibit the protein adsorption to the cationic surface at physiological pH, compatible with blood components and well tolerated upon intraperitoneal injection. The succinic anhydride-conjugated chitosan has the potential to serve as a coating material to prevent protein adsorption to cationic surfaces, which can be removed in a pH-responsive manner.

Sudden death associated with hypertrophic cardiomyopathy in an alpaca (Llama pacos).

A healthy, 3-year-old, intact male alpaca (Llama pacos) died suddenly and unexpectedly and had an unusual pattern of hypertrophic cardiomyopathy that was restricted to the interventricular septal and right ventricular myocardium. Grossly pale areas in the affected myocardium corresponded histologically to thickened and disorganized myofibers with excessive branching and marked nuclear pleomorphism. Mitoses were absent. Inflammation and fibrosis were minimal. A few thickened muscular arteries were scattered in the affected myocardium.

Infection of cesarean-derived colostrum-deprived pigs with porcine circovirus type 2 and Swine influenza virus.

Porcine circovirus type 2 (PCV2) and swine influenza virus (SIV) are important pathogens for porcine respiratory disease complex, which is economically significant worldwide. The pathogenesis of PCV2-SIV coinfection is unknown. In this study, we focused on establishing a challenge model for PCV2 to determine whether SIV influences PCV2 replication and increases the severity of PCV2-associated disease. Cesarean-derived colostrum-deprived pigs were inoculated intratracheally with cell culture medium only (negative control group), PCV2 only, or PCV2 followed 1 wk later with SIV H1N1. Two pigs from each group were necropsied at 12, 21, 28, and 35 d after inoculation. Coinfection with SIV did not increase the number of PCV2 genomic copies in serum or target tissues or the severity of microscopic lesions associated with PCV2 in lung or lymph node. The antibody titer to PCV2 did not differ significantly between PCV2-SIV- and PCV2-infected groups. In conclusion, SIV H1N1 did not influence PCV2 replication in dually infected pigs in this study.

Deployment performance and retrievability of the Cook Celect vena cava filter.

PURPOSE: To test the safety, performance, and retrievability of the Cook Celect vena cava filter. MATERIALS AND METHODS: Twenty female or castrated male sheep were implanted with two Celect filters in series, in the inferior vena cava. The animals were divided into five groups of four animals according to day of filter retrieval. Filter retrieval occurred at approximately 30, 60, 90, 180, and 360 days after implantation. At each time point, two sheep underwent retrieval attempts of both the cranial and caudal filters. These animals were recovered for 30 days, at which time healing was assessed. In two additional sheep at each time point, retrieval of only the cranial filter was attempted and the caudal filter was left in situ. These sheep were euthanized after retrieval, and the segment of vena cava encompassing the sites of both the retrieved filter and the filter left in situ was excised for gross and histopathologic analysis. RESULTS: Retrieval attempts occurred at 34, 62, 90, 188, and 393 days after implantation. All retrievals were successful (30 of 30). Tilt was detected in eight filters at implantation; six had self-centered before retrieval. At retrieval, no filter migration or deformation was reported. All filters were retrieved with acceptable levels of force. At each time point, there was evidence of mild intimal hyperplasia at the filter anchoring sites and no evidence of vena cava injury. CONCLUSIONS: The Celect vena cava filter was safely used as a retrievable filter for up to 393 days in an ovine model.

Cholangiectasis and duodenal diverticulosis in a farm-raised elk (Cervus elaphus).

A 6-year-old male elk presented in August with a 4-month history of weight loss and a 1-day history of being recumbent and unable to rise. The elk's body condition score was 1.5/5. Hematology and blood chemistry showed an inflammatory leukogram, mild electrolyte abnormalities, and elevated liver enzyme activities. Because of poor prognosis, the owner elected euthanasia. On necropsy, 8 diverticula were in the duodenum distal to the common bile duct, which was dilated and filled with feed material. Many intrahepatic bile ducts were dilated up to 5 cm, were filled with ingesta and gritty material, and had walls thickened up to 1.5 mm. On histologic examination, mural thickening of dilated bile ducts was because of increased fibrous connective tissue with inflammatory cell infiltration and hyperplastic and hypertrophic epithelial lining. Portal tracts diffusely contained hyperplastic bile ducts and had increased amounts of fibrous connective tissue. Abscesses that contained bacteria were scattered throughout the liver. Duodenal diverticula lacked the tunica muscularis, and the muscularis mucosa was hypertrophied. Caudal to some diverticula, the duodenal lumen was narrowed. An additional finding was embolic pneumonia with fungi morphologically and immunohistochemically consistent with Aspergillus spp.