A 16-year-old, 473-kg, Thoroughbred mare was referred to the Cornell University Hospital for Animals with a 1-year history of chronic cough, halitosis, weight loss, and lethargy. Nine months earlier, the mare had been treated for a bacterial or viral respiratory infection with a course of potentiated sulfonamides. During the 6-week treatment period, the owner reported that the horse had decreased appetite and had lost weight but that the respiratory signs seemed improved. More recently, over the last 2–3 months, the mare exhibited intermittent respiratory signs, inappetence, and weight loss. On presentation, the mare (body condition score 4/9) was alert and responsive and had a normal rectal temperature (100.6°F) and heart rate (40 beats/min), but was tachypneic (32 breaths/min). Her mucous membranes were pink and capillary refill time was normal (<2 seconds). During the examination, a nonproductive cough occurred intermittently and was associated with foul-smelling breath. Cardiothoracic auscultation was normal and a rebreathing examination disclosed decreased lung sounds in the cranioventral lung fields. Auscultation of abdomen was normal. Clinical laboratory tests identified the presence of mature neutrophilia (7.2 × 103/μL; reference range, 2.7–6.6 × 103/μL), hyperproteinemia (9.7 g/dL; reference range, 5.7–7.7 g/dL), hyperglobulinemia (7.1 g/dL; reference range, 2.4–4.4 g/dL), hyperfibrinogenemia (400 mg/dL; reference range, 0–200 mg/dL), and hypoalbuminemia (2.8 g/dL; reference range, 3–3.7 g/dL). Red cell indices (HCT, RBC numbers, MCV, RDW) were within normal limits. Serum electrolyte concentrations (sodium, potassium, chloride, calcium, and phosphorus) were normal, and CK and AST activities were decreased (95 and 161 U/L, respectively; reference range CK, 142–548 U/L; reference range AST, 199–374). Serum creatinine concentration, hepatic enzyme activities (SDH, GLDH, GGT), and serum bilirubin (indirect, direct) concentrations also were within the reference range. Thoracic radiography disclosed the presence of 3 lesions: Cranio-ventrally, there was lung consolidation and air bronchograms consistent with pneumonia. Caudo-dorsally, there was a single, oval, well-margined, soft tissue opacity that spanned 4 intercostal spaces and silhouetted with the diaphragm. Because this lesion silhouetted with the diaphragm, its abdominal extension could not be confirmed by radiography. Cranio-dorsally, within the abdomen and close to the diaphragm, were 2 well-marginated structures with fluid–gas interfaces that spanned 4 intercostal spaces (Fig 1). Based upon the radiographic findings, the gas accumulations were considered to represent abscesses within the liver or gas-filled segments of bowel. Thoracic sonography confirmed the presence of bilateral ventral lung consolidation consistent with pneumonia. The caudo-dorsal lung lesion, visible on radiographs, was not observed on ultrasound examination because it was surrounded by aerated lung. Sonography of the right cranio-dorsal abdomen confirmed that the liver contained an encapsulated, well-marginated, multi-loculated mass (or multi-focal masses) containing gas and a complex echogenicity fluid consistent with abscessation (Fig 2). Sonography was not able to determine the association between the liver abscess, which spanned the 13th through 16th intercostal spaces, and the focal craniodorsal lung lesion because the deeper and cranial aspects of the diaphragm and liver were obscured by aerated lung. Aspiration of the mass or biopsy of the hepatic tissue was not considered because of the potential risk of spreading the infection into the peritoneal or pleural cavities. Measurement of serum bile acids, although potentially helpful in cases of extensive hepatic abscessation, was not performed. A rectal examination was performed but no abnormalities were detected on palpation. An abdominocentesis failed to yield any peritoneal fluid. A transtracheal aspirate yielded degenerative neutrophils, moderate numbers of intracellular and extracellular Gram-negative rods, and occasional Gram-positive cocci indicative of a septic suppurative inflammation. Aerobic and anaerobic culture of the aspirate yielded Actinobacillus equuli and Peptostreptococcus asaccharolyticus, respectively. Blood culture yielded no bacterial growth. The mare was hospitalized for 5 days and treated with potassium penicillin1 22,000 IU/kg IV q6h, gentamicin sulfate2 6.6 mg/kg IV q24h, and metronidazole3 25 mg/kg per rectum q8h. She was nebulized4 q8h with a 25-mL solution containing 5 mL of acetylcysteine,5 1 mL of albuterol sulfate solution,6 and 19 mL of 0.9% saline.7 While hospitalized, the mare showed mild clinical improvement in her demeanor and appetite. At the time of her discharge, the client was instructed to administer chloramphenicol8 (50 mg/kg PO q8h) and omeprazole9 (1.1 mg/kg PO q24h) and to have the horse re-evaluated in 3 weeks. On the return visit, laboratory evaluation disclosed a persistent hyperproteinemia (8.6 g/dL), hyperglobulinemia (6.4 g/dL), hypoalbuminemia (2.4 g/dL), and neutrophilic leukocytosis (10,900/μL). Thoracic and abdominal ultrasound examination demonstrated an increase in the size of the hepatic abscesses within the right dorsal liver. Because of the poor response to treatment, the owner elected to euthanize the mare. A complete postmortem examination was performed approximately 20 hours after euthanasia. On gross examination, an encapsulated 18 × 15 × 5 cm abscess was found in the left caudo-dorsal lung. The mass communicated transdiaphragmatically with the left lateral liver lobe; the liver and lung were adhered to the diaphragm at the location of the mass. The abscess contained approximately 500 mL of white-tan thick liquid and an accumulation of inspissated material. An aseptic aspirate of the hepatic abscess subsequently yielded Fusobacterium necrophorum and Bacteroides vulgatus. Other findings included diffusely thickened and hypertrophic ileal musculature (1 cm wall thickness) containing approximately a dozen diverticula present in the antimesenteric border ranging in size from 1 mm3 to 2 × 1 × 1 cm, some of which were impacted with feed whereas others contained purulent material (Fig 3). There was evidence of moderate, diffuse peritonitis with fibrin strands present throughout the abdomen. No lesions consistent with cranioventral pneumonia were identified. All tissues were fixed in 10% neutral-buffered formalin, processed routinely for histopathology, and stained with hematoxylin and eosin (H&E). The hepatic abscess was characterized by a central area of liquefactive necrosis, fibrin, cellular debris, degenerate and nondegenerate neutrophils, lymphocytes, and extracellular bacterial rods surrounded by a fibrovascular capsule. The ileal musculature was diffusely hypertrophied except in areas of the diverticula. These diverticula were formed by layers of the longitudinal and circular ileal muscles forming serosal outpouchings. The lumina of the the diverticula were lined by variably inflamed mucosa and submucosa. Several diverticula contained a neutrophilic, lymphoplasmacytic inflammatory cell population that dissected through the muscular layers extending to within 1 mm of the serosal surface (Fig 4). To the authors' knowledge, this is the first reported case of a transdiaphragmatic hepato-pulmonary abscess in a horse. In contrast to cattle, hepatic abscessation in horses is uncommon and most often is a sequela to Streptococcus equi or Corynebacterium pseudotuberculosis infections1 or secondary to bacterial translocation from the gastrointestinal tract.2 Hepatic abscesses also develop secondary to penetrating foreign objects within the gastrointestinal tract.2-5 As occurs in cattle, caudal vena caval phlebitis and secondary embolic pneumonia may result from hepatic abscessation in horses.2, 6 However, neither sequelae were apparent in this case. Given the microbiologic results of a mixed anaerobic infection along with the presence of ileal diverticulitis, it is likely that translocation of bacteria through the compromised ileal wall either via the peritoneum or the portal circulation caused the hepatic abscess. In humans, diverticulitis of the small intestine or large colon has been associated the development of hepatic abscesses.7, 8 The virulence factors of F. necrophorum, which include leukotoxins, lipopolysaccharide, hemolysins, dermonecrotic toxins, and extracellular enzymes9, 10 likely resulted in tissue necrosis and subsequent extension of the hepatic abscess through the diaphragm and into the adjacent lung in this horse. A primary pulmonary abscess originally was considered possible, but the discrete and caudo-dorsal location of the affected lung along with the presence of intestinal diverticulitis made this less likely to be a primary event. The discrepancy between the imaging of the liver abscess and the location at necropsy is considered to have occurred because the left liver lobe extends to the right of the caudal vena cava in the horse. Small intestinal muscular hypertrophy typically is a condition of mature horses, and there is no reported breed or sex predisposition.11 The lesion often is found incidentally at postmortem examination. Suggested predisposing factors for small intestinal muscular hypertrophy include Anoplocephala perfoliata at the ileocecal junction, mucosal inflammation, uncontrolled peristalsis, and intestinal sand accumulation. An association between ileal muscular hypertrophy and ileal diverticula has been suggested.12, 11, 13-18 In contrast to the current case report, the most common clinical presentation of horses with small intestinal diverticula is chronic colic. In a retrospective study of 11 horses with idiopathic muscular hypertrophy, 10 horses presented with chronic colic, from 1 to 6 months duration, and a single horse presented with acute colic. Of these horses, 45% had small diverticula present in the ileum. Intestinal rupture and subsequent peritonitis also have been reported secondary to jejunal diverticulosis in 2 horses.16 In humans, the relationship between intestinal muscular hypertrophy and diverticula has been more defined. Most intestinal diverticula are thought to be acquired pulsion lesions. Luminal pressure is increased secondary to distorted smooth muscle contractions leading to formation of diverticula.19 Antemortem diagnosis of diverticula is difficult in veterinary medicine. The large size of horses, extensive nature of the gastrointestinal tract, and relatively small proportion of the intestine that may be affected make noninvasive diagnosis difficult. In human medicine, computed tomography is the diagnostic test of choice, but the finding of a diverticulum often is serendipitous during abdominal surgery. This case represents an unusual combination of clinical and postmortem findings and is the first report of a transdiaphragmatic abscess in a horse. Intestinal diverticulum should be considered in horses with nonspecific abdominal signs, peritonitis, or hepatic abscessation with atypical culture results. Conflict of Interest: Authors disclose no conflict of interest.

REASONS FOR PERFORMING STUDY A consistent and clinically relevant model for the induction of core lesions confined to the mid-metacarpal superficial digital flexor tendon (SDFT) has not been previously reported. Injection of bacterial collagenase is commonly used but often results in large, irregular and inconsistent lesions that disrupt the superficial tendon layers and epitenon. OBJECTIVE To develop and evaluate a new injection technique for collagenase induction of SDFT injury. METHODS Collagenase gel was injected into a physical columnar defect created by longitudinally placing a curved 16 gauge 8.89 cm needle in the mid-metacarpal SDFT in a randomly selected forelimb of 10 horses. A placebo treatment injection was performed 1 week later. Serial ultrasound examinations were performed. Horses were subjected to euthanasia at 2 (n = 2), 4 (n = 2), 8 (n = 4) and 16 (n = 2) weeks post treatment injection. Post mortem magnetic resonance imaging and histological analysis were performed. Gene expression (18S, SCX, TNC, TNMD, COL1A1, COL3A1, COMP, DCN, MMP1, MMP3 and MMP13), total DNA, glycosaminoglycan and collagen content were determined for experimental tendons (n = 10) and unaffected tendons (n = 9). RESULTS Mid-metacarpal SDFT core lesion induction was successful in all tendons with consistent lesion cross-sectional area and minimal epitenon disruption. Histology confirmed loss of normal tendon architecture after tendonitis induction and subsequent healing of the tendon core lesion. Compared with gene expression in unaffected tendons, several tested genes were significantly upregulated (COL1A1, COL3A1, TNMD, SCX, TNC, MMP13), while others showed significant downregulation (COMP, DCN, and MMP3). CONCLUSION Compared with the previously used direct injection of collagenase, this injection technique was easily performed and induced more consistent lesions that were mid-metacarpal and did not disrupt the epitenon. POTENTIAL RELEVANCE This model will allow for objective assessment of therapies for tendon regeneration in the mid-metacarpal SDFT prior to clinical trials and routine clinical application.

Nasopharyngeal and laryngeal evaluation is important when examining horses with upper airway signs for poor performance. Currently endoscopy is the most common method to evaluate the equine upper airway. Ultrasonography of the equine larynx has not previously been described. Using six cadaveric specimens and four standing horses, the ultrasonographic appearance of the equine larynx was established. A scanning technique, including useful acoustic windows and the normal ultrasonographic appearance at each site, is described. Ultrasound allowed visualization of portions of the hyoid apparatus, laryngeal cartilages, associated soft tissues, and intrinsic and extrinsic laryngeal musculature, that are not seen using endoscopy. Additionally, real-time ultrasound allowed observation of the movement of the vocal folds and the arytenoid cartilages during respiration. In three horses with arytenoid chondritis, ultrasonography aided in the diagnosis and localization of arytenoid abcessation and perilaryngeal inflammation. The establishment of this technique will serve as the basis for future investigations in the evaluation of clinical patients with upper airway abnormalities.

Somatostatin receptors expressed by insulinomas in 5 dogs were imaged in vivo by means of indium in 111 pentetreotide (OctreoScan) scintigraphy. The diagnosis in each dog was supported by the presence of hypoglycemia (<60 mg/dL), hyperinsulinemia (>20 microU/mL), and histopathologic review of neoplastic tissue. All insulinomas expressed high-affinity somatostatin receptors of subtype sst2, as shown by receptor autoradiography in vitro using 125I-[tyrosine3]-octreotide and 125I-[leucine8, Dtryptophan22, tyrosine25]-somatostatin-28 with an sst2 subtype-selective analogue. Scintigrams were obtained at 1, 4, 12, and 24 hours after the i.v. administration of 74-222 MBq of OctreoScan to each patient. Abnormal foci of activity were 1st observed from 1 hour after administration of the radioligand in dog 3, to 24 hours after its administration in dog 4; in dogs 1 and 2, abnormal foci of activity were visible from 12 hours. Dog 5 showed a questionable abnormal focus of activity at 12 hours, but not at 24 hours. Scintigraphy enabled accurate prediction of the anatomical location of the primary tumor in 1 of 4 dogs, but was unable to differentiate a right- from a left-pancreatic lobe tumor, or vice versa, in 3 dogs; the 5th dog had equivocal results. 111In-pentetreotide scintigraphy is a useful diagnostic adjunct to the clinical evaluation of the insulinoma patient, but is unable to localize the tumor in some cases.

Integrations of woodchuck hepatitis virus (WHV) DNA and rearrangements of the N-myc 2 gene have been detected frequently in hepatocellular carcinoma (HCC) of Eastern woodchucks (Marmota monax) chronically infected with WHV. Fifty-five hepatocellular neoplasms and matched nontumor hepatic tissue specimens obtained postmortem from 13 chronic WHV carriers were analyzed and the frequency of WHV DNA integrations and of N-myc rearrangements compared in tumors of different size and histologic grade. Four small tumor nodules were classified histologically as adenomas and integrated sequences of WHV DNA were detected in two of the four tumor nodules. In one of the two nodules, there was evidence of N-myc rearrangement. Fifty-one neoplasms were classified as HCC. Seven were grade 1 HCCs. WHV DNA integrations were demonstrated in 43% but none had N-myc rearrangements. Twenty grade 2 HCCs had WHV DNA integrations in 80% and in 38% N-myc rearrangements were present. Twenty-four grade 3 HCCs had integrations of WHV DNA in 79% and N-myc rearrangements in 74%. In two other grade 3 HCCs, rearrangements of N-myc were detected in the absence of WHV DNA integrations. The 12 largest tumors in the series all were grade 2 or 3 HCCs, and in 83%, both WHV DNA integrations and N-myc rearrangements were demonstrated. In conclusion, molecular changes observed in this study suggest a progression of genetic alterations providing either a significant proliferative stimulation and/or a growth advantage in hepatocarcinogenesis of woodchucks with chronic WHV infection.

The length of canine gestation is 65 days from the luteinizing hormone (LH) surge. Early and accurate determination of canine gestational age is useful for predicting and managing parturition. We performed a retrospective study on fetal measurements obtained by transabdominal ultrasonographic examination of 83 bitches (32 breeds) to estimate gestational age. Gestational age was estimated using two published tables correlating either (1). embryonic vesicle diameter (EVD), crown-rump length (CRL), body diameter (BD), and biparietal diameter (HD) to the LH surge in mid-gestational beagles or (2). BD and HD to parturition in late-gestation retrievers. Parturition date was predicted by obtaining the difference between the gestational age estimate and 65 days. Bitches were divided into four body weight (BW) groups based on nonpregnant body weight: small (9-20 kg), large (>20-40 kg), and giant (>40 kg). Mean+/-S.D. litter size (LS) was calculated for each BW group. The BW groups were then divided into small, average, or large LS groups. The accuracy of the prediction was not affected by LS but was affected by maternal body weight for small and giant BW groups only. When adjusted for weight, the accuracy of prediction within +/-1 day and +/-2 day intervals was 75 and 87%, respectively. Using stepwise logisitic regression, the most accurate prediction of parturition date was obtained when fetuses were measured at 30 days after the LH surge, regardless of body weight or LS. Parturition date predictions made after 39 days of gestation using only biparietal and BD fetal measurements were <50% accurate within +/-2 days.

OBJECTIVE To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. ANIMALS 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. PROCEDURE Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. RESULTS For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

OBJECTIVE To determine whether sensitivity of detecting an anomalous portosystemic blood vessel during operative mesenteric portography varied with patient positioning. DESIGN Retrospective study. ANIMALS 34 dogs with a portosystemic shunt diagnosed via scintigraphy or surgery. PROCEDURE Portograms were evaluated for a portosystemic blood vessel. Sensitivity was calculated from results obtained with dogs in left lateral, right lateral, and dorsal recumbency and from results obtained with dogs in 2 or 3 positions. Differences in sensitivity among positions and between 2 examiners were evaluated. RESULTS Sensitivity was 85, 91, and 100% in dorsal, right lateral, and left lateral recumbency, respectively. Sensitivity was lower in dorsal recumbency than in left lateral recumbency, although differences were not significant. There was no significant difference between sensitivity of results obtained in dorsal and right lateral recumbency or right lateral and left lateral recumbency. Sensitivity for combined right lateral and dorsal positions was 97%, which was better than that in dorsal recumbency alone, although the difference was not significant. Because sensitivity in left lateral recumbency was 100%, there was no need to evaluate the improvement obtained by combining the result of this position with the results of other positions. CONCLUSION AND CLINICAL RELEVANCE Results of mesenteric portography varied with patient positioning. The optimal position varied among patients but left lateral recumbency may be better and dorsal recumbency worse. Sensitivity may be improved by performing the test with the patient in orthogonal recumbent positions.

The efficacy, safety, and metabolic consequences of rapid weight loss in privately owned obese cats by means of a canned weight-reduction diet and the influence of orally administered L-carnitine on rate of weight loss, routine clinical evaluations, hepatic ultrasonography, plasma amino acid profiles, and carnitine analytes were evaluated. A double-blinded placebo-controlled design was used with cats randomly divided into 2 groups: Group 1 (n = 14) received L-carnitine (250 mg PO q24h) in aqueous solution and group 2 (n = 10) received an identical-appearing water placebo. Median obesity (body condition scores and percentage ideal body weight) in each group was 25%. Caloric intake was restricted to 60% of maintenance energy requirements (60 kcal/kg) for targeted ideal weight. The reducing formula was readily accepted by all cats. Significant weight loss was achieved by week 18 in each group without adverse effects (group 1 = 23.7%, group 2 = 19.6%). Cats receiving carnitine lost weight at a significantly faster rate (P < .05). Significant increases in carnitine values developed in each group (P < .02). However, significantly higher concentrations of all carnitine moieties and a greater percentage of acetylcarnitine developed in cats of group 1 (P < .01). The dietary formula and described reducing strategy can safely achieve a 20% weight reduction within 18 weeks in obese cats. An aqueous solution of L-carnitine (250 mg PO q12h) was at least partially absorbed, was nontoxic, and significantly increased plasma carnitine analyte concentrations as well as rate of weight loss.

A prospective clinical study in dogs with transudative abdominal effusions examined the clinical usefulness of the serum albumin-effusion albumin (SA-EA) gradient. In humans, the SA-EA gradient facilitates classification of abdominal effusion, with a gradient > or = 1.1 indicating the presence of portal hypertension. Gradient values proved useful for predicting therapeutic response to sodium restriction and diuresis in humans. Of 49 dogs evaluated, 25 had hepatobiliary disease (group 1) and 24 had other nonhepatobiliary conditions (group 2). Portal hypertension was clinically suspected in 24 of 25 dogs in group 1 and in 15 of 24 dogs in group 2. A broad range of SA-EA gradients was found. A gradient > or = 1.1 was found in 22 of 25 (88.0%) dogs with liver disease and in 14 of 24 (58.3%) dogs with other disorders. The median SA-EA gradient was higher in group 1 than in group 2, with values of 1.4 (range, 0.7-3.1) and 1.1 (range, 0.3-2.6), respectively (P < .04). Considerable overlapping of SA-EA gradients occurred between groups and among dogs with diverse conditions such that gradient values could not distinguish dogs with hepatobiliary disease from dogs with other conditions. The overall diagnostic accuracy of the SA-EA gradient in predicting portal hypertension in dogs with and without hepatobiliary disease (69.4%) exceeded that of hypoalbuminemia (57.1%). These findings suggest that portal hypertension is a predominant force in formation of transudative abdominal effusion in dogs with hepatobiliary disease and in dogs with other disorders. Whether the SA-EA gradient can be used to guide therapeutic mobilization of effusion in dogs remains to be proved.

Pulmonary lymphomatoid granulomatosis was diagnosed in a 9-year-old castrated male domestic shorthair cat with a history of coughing, lethargy, and anorexia. Radiographic examination revealed multiple pulmonary opacities, consolidation of left lung lobes, and enlarged tracheobronchial lymph nodes. Cytologic examination of impression smears of abnormal pulmonary tissue revealed erythrocytes, lymphocytes, and macrophages, with scattered atypical lymphocytes and binucleate cells. Histopathologic evaluation of abnormal lung tissue revealed multiple, coalescing, densely cellular nodules composed of anaplastic and pleomorphic lymphocytes, with scattered binucleate and multinucleate cells. Marked infiltration and effacement of bronchiolar and vascular smooth muscle were present. These features are characteristic of lymphomatoid granulomatosis. To the authors' knowledge, this is the first report of pulmonary lymphomatoid granulomatosis in a cat.

Glomerular filtration rate (GFR) and renal volume were evaluated in dogs with confirmed portosystemic vascular anomalies (PSVA) before and after surgical ligation of their PSVA. Pre- and postligation CBC, serum biochemistry, urinalysis, abdominal ultrasonography with measurement of renal volume, and per rectal scintigraphy were performed to document resolution of abnormalities consistent with portosystemic shunting. GFR was estimated by plasma 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance before (n = 21) and after (n = 12) surgical correction of PSVA. Preligation 99mTc-DTPA GFR was increased (median, 5.64 mL/minute/kg; range, 3.53-8.49 mL/minute/kg; reference range, 2.83-4.47 mL/minute/kg) in 81% (17/21) of dogs. Postligation 99mTc-DTPA GFR decreased in all 12 evaluated dogs (median change = -42%; P < .001). Preligation renal volume was above the reference range for the left and right kidneys in 71% (10/14) and 69% (11/16) of dogs evaluated, respectively. Right renal volume decreased significantly (n = 5; median change, -45%; P = .03) after surgical ligation of PSVA. These findings document increased GFR and renal volume in dogs with PSVA, which may explain in part the low blood urea nitrogen and serum creatinine concentrations encountered in these dogs. Knowledge of changes in GFR associated with PSVA ligation may prove helpful in the anesthetic, drug, and dietary management of affected dogs.

We describe 4 young male Doberman Pinschers (3 littermates and 1 unrelated dog) with a syndrome resembling idiopathic or noncirrhotic portal hypertension of humans. Each dog was evaluated for a hepatopathy resulting in portal hypertension, development of portosystemic collateral vessels, and hepatic encephalopathy. These dogs differ from previous reports of young dogs with hepatic insufficiency associated with portal hypertension and acquired portal systemic shunting by their lack of intrahepatic arteriovenous fistulae, portal vein atresia, or intrahepatic fibrosis. Clinicopathologic features included erythrocyte microcytosis, normal to mildly increased liver enzyme activities, increased concentrations of serum bile acids, reduced plasma indocyanine green clearance, and normal total bilirubin concentration. Abdominal ultrasonography disclosed a small liver and portosystemic collateral vessels. Radiographic imaging studies confirmed hepatofugal portal circulation and discounted hepatic arteriovenous fistulae. Histopathologic features in liver tissue from each dog were similar and consistent in all sections examined. Common findings included increased cross-sectional views of hepatic arterioles; hepatic lobular atrophy; scanty increase in connective tissue around some large portal triads; and absence of inflammation, disturbed lobular architecture, bile duct proliferation, or intrahepatic cholestasis.

Woodchucks were used to study the antiviral activity and toxicity of fialuridine (FIAU; 1,-2′deoxy-2′fluoro-1-β-d-arabinofuranosyl-5-iodo-uracil). In an initial experiment, groups of six chronic woodchuck hepatitis virus (WHV) carrier woodchucks received daily doses of FIAU by intraperitoneal injection for 4 weeks. At 0.3 mg/kg/d, the antiviral effect was equivocal, but at 1.5 mg/kg/d, FIAU had significant antiviral activity. No evidence of drug toxicity was observed during the 4-week period of treatment or during posttreatment follow-up. In a second experiment, groups of nine WHV carriers or uninfected woodchucks were given 1.5 mg/kg/d of FIAU orally for 12 weeks, and the results compared with placebo-treated controls. After 4 weeks, the serum WHV-DNA concentration in the FIAU-treated carrier group was two to three logs lower than that in the placebo-treated group. After 12 weeks of FIAU treatment, serum WHV DNA was not detectable by conventional dot-blot analysis, hepatic WHV-DNA replicative intermediates (RI) had decreased 100-fold, and hepatic expression of WHV core antigen was remarkably decreased. No evidence of toxicity was observed after 4 weeks, but, after 6 to 7 weeks, food intake decreased and, after 8 weeks, the mean body weights of woodchucks treated with FIAU were significantly lower than controls. Anorexia, weight loss, muscle wasting, and lethargy became progressively severe, and all FIAU-treated woodchucks died or were euthanized 78 to 111 days after treatment began. Hepatic insufficiency (hyperbilirubinemia, decreased serum fibrinogen, elevated prothrombin time), lactic acidosis, and hepatic steatosis were characteristic findings in the final stages of FIAU toxicity in woodchucks. The syndrome of delayed toxicity in woodchucks was similar to that observed previously in humans treated with FIAU, suggesting that the woodchuck should be valuable in future investigations of the molecular mechanisms of FIAU toxicity in vivo and for preclinical toxicological evaluation of other nucleoside analogs before use in patients.