Myenteric ganglionitis and intestinal leiomyositis in a Jack Russell terrier.

A 9-year, 6-month old spayed female Jack Russell terrier presented with a 3-week history of intermittent vomiting, diarrhoea and weight loss. Serum biochemistry demonstrated severe panhypoproteinaemia, mild hypocalcaemia and mild hypocholesterolaemia, consistent with protein-losing enteropathy. Full-thickness biopsies obtained from the stomach and different sections of small intestine demonstrated histological features of both myenteric ganglionitis and early intestinal leiomyositis. Complete resolution of clinical signs occurred within 1 week of implementing immunosuppressive therapy. At the time of writing, 9 months following diagnosis, the dog remains in remission.

Biological variation of serum canine calprotectin concentrations as measured by ELISA in healthy dogs.

Calprotectin is a useful biomarker of inflammation in dogs. However, the biological variation of serum canine calprotectin is unknown. Indices of biological variation were determined in serial serum samples (n=147) from 11 healthy dogs (males/females: 4/7, median age: 5 years): analytical (3.0%), intra-individual (29.9%), and inter-individual variation (33.2%), reciprocal index of individuality (1.1), and index of heterogeneity (4.9). Serum calprotectin concentrations measured by ELISA and by the previous radioimmunoassay were highly correlated, but a constant and proportional bias exists between both assays. A de novo ELISA-reference interval (RI) for serum calprotectin concentration was established (0.6-11.8mg/L). Moderate changes in serum calprotectin (minimum critical difference: 6.4mg/L) between sequential measurements are needed to be considered relevant, and a population-based RI may or may not be appropriate for serum calprotectin.

Variability of Symmetric Dimethylarginine in Apparently Healthy Dogs.

BACKGROUND: Symmetric dimethylarginine (SDMA) is a screening tool for early kidney dysfunction and monitoring treatment in cases of chronic kidney disease (CKD). There are no current studies describing the suitability of this test for use with published population-based reference intervals. HYPOTHESIS/OBJECTIVES: To determine the components of biological variability, the index of individuality (IOI), the critical difference between sequential measurements (CD ) and the number of measurements required to assess the homeostatic set point (HSP), for both SDMA and serum creatinine (sCr), in apparently healthy dogs. ANIMALS: Twenty apparently healthy adult dogs owned by clients or staff at a veterinary teaching hospital. METHODS: Prospective, observational study. Blood was collected from each dog on 9 occasions, and SDMA and sCr were measured in duplicate using commercially available assays. RESULTS: SDMA and sCr had intermediate and low IOI values of 0.87 and 0.28, respectively. The CD of SDMA and sCr, was 1.34 µg/dL and 0.89 µmol/L, respectively. The sample numbers required for estimation of an individual's HSP (with 90 and 95% CI) for SDMA and sCr were 8 and 45, and 2 and 12 sequential measurements, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on our findings, in comparison to sCr, SDMA is better suited for use with population-based reference intervals. False-negative test results could occur when comparing a single test result from an individual to such intervals. Ideally CD should be used with sequential measurements.

The relationship of serum cobalamin to methylmalonic acid concentrations and clinical variables in cats.

BACKGROUND: Serum cobalamin concentration [CBL] suggests CBL deficiency in cats but serum methylmalonic acid concentration [MMA] more accurately indicates CBL deficiency. OBJECTIVE: To examine the ability of [CBL] to predict CBL deficiency defined by increased [MMA], and relationships of [CBL] and [MMA] with select clinical and clinicopathological variables. ANIMALS: One hundred sixty-three client-owned cats with [CBL] measurements, 114 cats with simultaneous [MMA] measurements; 88 cats with medical information. METHODS: Prospectively collected [CBL] and [MMA] were compared using scatter plots, receiver operating characteristic and correlative analyses with historical [CBL] thresholds and those identified in the study. [CBL] and [MMA] were compared retrospectively to specific clinical and clinicopathological variables. RESULTS: [CBL] correlated negatively with [MMA] (τ = -0.334, P < .0001). [MMA] ≥ 1,343 nmol/L identified CBL deficiency. [CBL] = 209 pg/mL optimized sensitivity (0.51), specificity (0.96), PPV (0.89), and NPV (0.74) for detecting [MMA] ≥ 1,343 nmol/L. Prevalence of CBL deficiency was 42% (48/114) when defined by [MMA] ≥ 1,343 nmol/L versus 23% (27/114) by [CBL] ≤ 209 pg/mL. Unexpectedly, 23 and 45% of 48 cats with [MMA] ≥ 1,343 nmol/L had [CBL] > 900 pg/mL and 290 pg/mL (historical thresholds). [CBL] correlated with mean corpuscular volume (τ = -0.199, P = .013) and [MMA] with hematocrit (τ = -0.28, P = .006). CONCLUSIONS AND CLINICAL IMPORTANCE: Cobalamin deficiency ([MMA] ≥ 1,343 nmol/L) occurred in 42% of cats and is predicted with high specificity by [CBL] ≤ 209 pg/mL. CBL status correlates with microcytosis and anemia. Discordance between [CBL] and [MMA] cautions against relying on any single marker for determining CBL status.

Cobalamin in companion animals: diagnostic marker, deficiency states and therapeutic implications.

Measurement of the water-soluble vitamin cobalamin has long been of interest as a marker of gastrointestinal disease in companion animals due to the highly localized presence of cobalamin receptors in the ileum. An increasing body of evidence suggests that cobalamin deficiency is an important co-morbidity in many companion animal patients with gastrointestinal and pancreatic disease. Congenital disorders of cobalamin absorption and cellular metabolism are also increasingly recognized in companion animal breeds. The early recognition of these disorders and timely treatment with parenteral cobalamin can be life-saving. In this article, the normal mechanisms of cobalamin absorption, the use of cobalamin as a marker of intestinal disease and data on the prevalence of hypocobalaminemia in a variety of diseases are described. The prognostic impact of and rational therapy for hypocobalaminemia in domestic animals are discussed.

Development and analytical validation of an enzyme-linked immunosorbent assay (ELISA) for the measurement of alpha(1)-proteinase inhibitor in serum and faeces from cats.

The objective of this study was to develop and analytically validate an ELISA for the measurement of alpha(1)-proteinase inhibitor (α(1)-PI) in serum and faeces from cats. Lower detection limit, linearity, accuracy, precision, reproducibility, and reference intervals were determined. The lower detection limits were 0.02 g/L for serum and 0.04 µg/g for faeces. The observed-to-expected (O/E) ratios for serial dilutions of serum and faecal samples ranged from 100.0 to 129.7% (mean±SD: 112.2±9.9%) and 103.5 to 141.6% (115.6±12.8%), respectively. The O/E ratios for samples spiked with seven known concentrations of α(1)-PI ranged from 82.3 to 107.8% (94.7±7.6%) for serum, and 78.5 to 148.7% (96.8±18.2%) for faeces. The coefficients of variation for intra-assay and inter-assay variability were <7.9% and <12.1% for serum, and 5.3%, 11.8%, 14.2%, and 7.7%, 10.2%, 20.4% for faeces, respectively. Reference intervals were 0.6-1.4 g/L for serum and upto 1.6 µg/g for faeces. We conclude that this ELISA is sufficiently linear, accurate, precise, and reproducible for clinical evaluation.

Biological variability of C-reactive protein and specific canine pancreatic lipase immunoreactivity in apparently healthy dogs.

BACKGROUND: C-reactive protein (CRP) and specific canine pancreatic lipase immunoreactivity (Spec cPL) are biomarkers of generalized or nonspecific inflammation and pancreatic inflammation in dogs, respectively. The extent of inter- and intraindividual variation over time of these analytes is not well defined in dogs. The minimal critical difference for sequential determinations of these markers (ie, the smallest change necessary to represent physiological change rather than biological variation), has not been defined. OBJECTIVES: To determine the inter- and intraindividual variability (CV(G) and CV(I) ) and minimal critical difference for sequential determinations of serum CRP and Spec cPL concentrations in apparently healthy dogs. ANIMALS: Eleven apparently healthy dogs owned by staff or students at a veterinary teaching hospital. METHODS: Blood was collected repeatedly at varying intervals over 12 weeks. CRP and Spec cPL concentrations were determined with commercially available assays. Indices of inter-, intraindividual, and assay variability and 1-sided minimal critical differences for sequential concentrations were calculated. RESULTS: For CRP, CV(G) was 90.8%, CV(I) was 115.5%, and the analytical variability (CV(A) ) was 6.3%; the index of individuality was 0.74, and 1-sided critical difference was 269.9%. For Spec cPL, CV(G) = 49.48%, CV(I) = 193.8%, CV(A) = 8.4%, index of individuality = 0.24, and 1-sided critical difference was 452.6%. CONCLUSIONS AND CLINICAL IMPORTANCE: A population-based reference range is appropriate for Spec cPL, but questionable for CRP in dogs. Large changes in serial measurements of Spec cPL are necessary to infer clinical importance, more modest changes in CRP are likely to be meaningful.

Relationships between low serum cobalamin concentrations and methlymalonic acidemia in cats.

BACKGROUND: Serum cobalamin concentrations below reference range are a common consequence of gastrointestinal disease in cats. Serum cobalamin 867 nmol/L. Sensitivity and specificity of serum cobalamin concentrations 867 nmol/L were analyzed using a receiver-operator characteristic curve. RESULTS: There was a negative correlation between serum cobalamin and MMA concentrations (Spearman's r=-0.74, P < 0.0001). The prevalence of MMA >or= 867 nmol/L in cats with serum cobalamin 867 nmol/L. No significant difference in serum folate concentrations was detected between affected and unaffected cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Elevated MMA concentrations, suggesting cobalamin deficiency, are common in cats with serum cobalamin

Early biochemical and clinical responses to cobalamin supplementation in cats with signs of gastrointestinal disease and severe hypocobalaminemia.

Domestic cats with small intestinal disease may develop cobalamin deficiency because of reduced small intestinal uptake of this vitamin. This study assessed the impact of cobalamin deficiency on biochemical and clinical findings in cats with intestinal disease. Nineteen pet cats, all with severe hypocobalaminemia (< or =100 ng/L) and histories of gastrointestinal signs, were studied. Cats received cobalamin, 250 microg SC once weekly, for 4 weeks. Biochemical indices of cobalamin availability (e.g., serum methylmalonic acid, homocysteine, and cysteine concentrations), serum feline trypsinlike immunoreactivity (fTLI) and serum folate concentrations, and clinical findings were recorded at the start of the study and after 4 weeks of cobalamin therapy. Serum methylmalonic acid (MMA) concentrations (median; range) decreased after cobalamin supplementation (5373.0; 708.5-29,329.0 versus 423.5; 214.0-7219.0 nmol/L, P < .0001). Serum homocysteine concentrations were not significantly altered (mean +/- SD 8.2 +/- 2.9 versus 10.3 +/- 4.5 micromol/L, P = .1198), whereas cysteine concentrations increased significantly (122.3 +/- 38.8 versus 191.5 +/- 29.4 micromol/L, P < .0001). Mean body weight increased significantly after cobalamin therapy (3.8 +/- 1.1 versus 4.1 +/- 1 kg, P < .01), and the average body weight gain was 8.2%. Significant linear relationships were observed between alterations in serum MMA and fTLI concentrations and the percentage body weight change (P < .05 for both, Pearson r2 = 0.26 and 0.245, respectively). Mean serum folate concentration decreased significantly (mean +/- SD 19 +/- 5 microg/L versus 15.4 +/- 6.2 microg/L, P < .001). Reduced vomiting and diarrhea were observed in 7 of 9 and 5 of 13 cats, respectively. These results suggest that cobalamin supplementation in cats with small intestinal disease and severe hypocobalaminemia is associated with normalization of biochemical test results and improvements in clinical findings in most affected cats.

Fecal alpha1-proteinase inhibitor concentration in dogs receiving long-term nonsteroidal anti-inflammatory drug therapy.

BACKGROUND: Fecal alpha(1)-proteinase inhibitor (alpha(1)-PI) clearance is a reliable, noninvasive marker for protein-losing enteropathy (PLE) in human beings. An assay for measurement of this protein in the dog has been developed and validated and may be useful for the investigation of gastrointestinal disease in this species. Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently are administered to dogs and may have adverse effects on the gastrointestinal tract, including gastroduodenal ulceration and altered mucosal permeability. The value of fecal alpha(1)-PI measurement in detecting unrelated gastrointestinal disease may be limited in dogs on NSAID therapy, but alpha(1)-PI may be a useful marker for NSAID-induced gastrointestinal damage. OBJECTIVE: The aim of this study was to evaluate the effects of long-term administration of NSAIDs on fecal alpha(1)-PI concentrations in dogs. METHODS: Fecal samples were collected from 2 groups of dogs: 1) 21 clinically-healthy client-owned dogs without signs of gastrointestinal disease and receiving no NSAIDs and 2) 7 dogs referred for investigation and treatment of orthopedic disorders; the dogs had received either meloxicam or carprofen daily for at least 30 days. Fecal alpha(1)-PI concentration was measured by ELISA. RESULTS: Fecal alpha(1)-PI concentrations, expressed as micro g/g of feces, were not significantly different between groups 1 and 2 (median [range], group 1: 9.9 micro g/g [0.0-32.1 micro g/g]; group 2: 5.6 micro g/g [1.1-32.3 micro g/g]; P =.81). CONCLUSIONS: These results suggest that use of cyclooxygenase-2-selective NSAIDs, such as carprofen and meloxicam, does not significantly affect fecal alpha(1)-PI measurements. However, study numbers were small, and larger prospective trials are required to assess more accurately the gastrointestinal effects of NSAIDs in dogs.

Fecal alpha1-proteinase inhibitor concentration in dogs with chronic gastrointestinal disease.

BACKGROUND: Fecal alpha(1)-proteinase inhibitor (alpha(1)-PI) clearance is a reliable, noninvasive marker for protein-losing enteropathy in human beings. An assay for use in dogs has been developed and validated. OBJECTIVE: The aim of this study was to evaluate fecal alpha(1)-PI concentration in dogs with chronic gastrointestinal disease, compared with healthy dogs, and to assess its correlation with serum albumin concentration. METHODS: Fecal samples were collected from 2 groups of dogs. Group 1 consisted of 21 clinically healthy client-owned dogs without signs of gastrointestinal disease. Group 2 consisted of 16 dogs referred for investigation of suspected gastrointestinal disease. On the basis of gastric and duodenal biopsies, group 2 was further subdivided into dogs with normal histology (n = 9) and those with histologic abnormalities (n = 7: inflammatory bowel disease, n = 3; lymphangiectasia, n = 4). An ELISA was used to measure alpha(1)-PI concentrations in fecal extracts. RESULTS: Fecal alpha(1)-PI concentrations, expressed as micro g/g of feces, were not significantly different between groups 1 and 2 as a whole. However, fecal alpha(1)-PI concentrations (median, minimum-maximum) were significantly higher in dogs with gastrointestinal diseases associated with histologic abnormalities (60.6 micro g/g, 7.4-201.7 micro g/g) compared with dogs with normal histology (3.8 micro g/g, 0.7-74.0 micro g/g) and control dogs (9.9 micro g/g, 0.0-32.1 micro g/g). There was no significant correlation between fecal alpha(1)-PI and serum albumin concentrations in dogs with gastrointestinal disease. CONCLUSIONS: Increased fecal alpha(1)-PI concentration may signal the need to obtain gastrointestinal biopsies for a final diagnosis. Fecal alpha(1)-PI concentration may be a useful test for early detection of protein-losing enteropathy before decreases in serum albumin concentration can be detected.

Comparison of direct and indirect tests for small intestinal bacterial overgrowth and antibiotic-responsive diarrhea in dogs.

Controversy exists over the diagnosis of idiopathic small intestinal bacterial overgrowth (SIBO) in dogs and some clinicians use the term antibiotic-responsive diarrhea (ARD) in preference. However, whether such terms are interchangeable is not clear. To examine the relationship between duodenal bacterial numbers and a clinical response to antibiotics, SIBO and ARD were defined by nonoverlapping criteria. Quantitative duodenal juice bacteriology and indirect serum biochemical tests were used to assess small intestinal bacterial populations in 30 dogs with gastrointestinal disorders, including 9 with ARD. Serum total unconjugated bile acid (TUBA) concentrations were measured in all dogs, serum folate and cobalamin concentrations were measured in 29 of 30 dogs, and quantitative culture of duodenal juice was performed in 22 of 30 dogs. Serum TUBA concentrations also were measured in samples from 38 control dogs. Twenty of 22 affected (clinical) dogs in which quantitative bacteriology was performed were classified as having SIBO (>10(5) colony-forming units of total bacteria per milliliter of duodenal juice), but bacterial numbers did not differ significantly between dogs with ARD and dogs with other disorders. Increased folate (19/29), decreased cobalamin (16/ 29), or a combination (9/29) were common, but increased TUBA concentrations were documented in only 5 of 30 clinical dogs. Again, no significant differences were observed between dogs with ARD and those with other disorders, and a similar proportion (5/38) of controls had abnormally high TUBA concentrations. Finally, no significant differences were noted when duodenal bacteriology and TUBA concentrations were assessed before and during antibiotic therapy. These results question the utility of quantitative duodenal juice bacteriology and indirect biochemical marker tests for SIBO in the investigation of canine gastrointestinal disorders.

Metabolism of amino acids in cats with severe cobalamin deficiency.

OBJECTIVE: To validate an automated chemiluminescent immunoassay for measuring serum cobalamin concentration in cats, to establish and validate gas chromatography-mass spectrometry techniques for use in quantification of methylmalonic acid, homocysteine, cysteine, cystathionine, and methionine in sera from cats, and to investigate serum concentrations of methylmalonic acid, methionine, homocysteine, cystathionine, and cysteine as indicators of biochemical abnormalities accompanying severe cobalamin (vitamin B12) deficiency in cats. SAMPLE POPULATION: Serum samples of 40 cats with severe cobalamin deficiency (serum cobalamin concentration < 100 ng/L) and 24 control cats with serum cobalamin concentration within the reference range. PROCEDURE: Serum concentrations of cobalamin were measured, using a commercial automated chemiluminescent immunoassay. Serum concentrations of methylmalonic acid, methionine, homocysteine, cystathionine, and cysteine were measured, using gas chromatography-mass spectrometry, selected ion monitoring, stable-isotope dilution assays. RESULTS: Cats with cobalamin deficiency had significant increases in mean serum concentrations bf methylmalonic acid (9,607 nmol/L), compared with healthy cats (448 nmol/L). Affected cats also had substantial disturbances in amino acid metabolism, compared with healthy cats, with significantly increased serum concentrations of methionine (133.8 vs 101.1 micromol/L) and significantly decreased serum concentrations of cystathionine (449.6 vs 573.2 nmol/L) and cysteine (142.3 vs 163.9 micromol/L). There was not a significant difference in serum concentrations of homocysteine between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Cats with gastrointestinal tract disease may have abnormalities in amino acid metabolism consistent with cobalamin deficiency. Parenteral administration of cobalamin may be necessary to correct these biochemical abnormalities.

The effect of ex vivo refrigerated storage and cell preservation solution (Cyto-Chex II) on CD11b expression and oxidative burst activity of dog neutrophils.

The expression of CD11b and oxidative burst activity of dog neutrophils undergoing ex vivo refrigerated storage was studied using flow-cytometry . Additionally, the effect of a proprietary cell stabilization reagent (Cyto-Chex) on the expression of CD11b and oxidative burst activity was studied. Expression of CD11b was very high (>90% positive) on dog neutr ophils isolated from peripheral blood. Dog neutrophils showed a rapid and sustained increase in CD11b antigen density (P<0.01) during refrigerated storage, this increase was prevented by treatment with Cyto-Chex but was not completely blocked on the first day. There were no significant differences in mean antigen density between any days in the non-preserved group or between Days 1 to 4 in the Cyto-Chex treated group. The non-treated group showed significantly greater mean antigen density at all time points when compared to the preservative treated group (P<0.0001). Treatment with Cyto-Chex did not interfere with measurement of oxidative burst function on the first 2 days. Alterations of both resting oxidative activity and stimulated response were observed over time in both treated and untreated blood samples. Cyto-Chex treated samples showed a dramatic, significant decline in stimulated response after the third day of storage (P<0.001), while non-treated cells showed steadily increasing, but non-significant differences in stimulated response. Cyto-Chex was demonstrated to be a useful reagent for stabilization of dog neutrophil membrane antigens during storage, however this reagent is not recommended for preservation of cells for functional assays.

Levels of total alpha-macroglobulin and trypsin-like immunoreactivity are poor indicators of clinical severity in spontaneous canine acute pancreatitis.

Trypsin-like immunoreactivity and total alpha-macroglobulin levels were assessed in serum and plasma samples taken at presentation from 60 cases of spontaneous canine acute pancreatitis of varying clinical severity. Total alpha-macroglobulin was significantly decreased in all severity groups when compared to 119 healthy controls, however there were no significant differences between severity groups. Trypsin-like immunoreactivity was significantly elevated above assay reference range in all groups. Trypsin-like immunoreactivity was significantly elevated in dogs with severe disease when compared to those with mild disease. These results suggest that zymogen release and protease activation, while components of the pathology of spontaneous canine acute pancreatitis, are not directly associated with the onset of multiple organ failure seen in the most severe cases.

Detection and measurement of canine alpha-macroglobulins by enzyme immuno-assay.

The alpha-macroglobulins are broad-specificity protease inhibitors important in the regulation and clearance from circulation of biologically active proteases. Inappropriate protease activation may be a feature of canine acute pancreatitis and the ability of the animal to clear these proteases may be important in determining survival. An enzyme immunoassay for the detection and measurement of canine alpha-macroglobulins in plasma samples was developed. A reference range for the canine alpha-macroglobulins of 1.20-2.72 mg ml-1 was established from a panel of canine plasma samples, and the stability of the alpha-macroglobulins in plasma samples stored at 4 degrees C was investigated. Changes in the level of the alpha-macroglobulins during disease states involving increased endogenous protease activity can now be investigated using a rapid, repeatable and quantifiable assay.

Tumor necrosis factor-alpha at presentation in 60 cases of spontaneous canine acute pancreatitis.

Tumor necrosis factor-alpha (TNF) is a pleiotropic cytokine with profound and broad ranging effects on many cell types. There have been few publications investigating the role of TNF in spontaneous disease processes of dogs, particularly the role of this cytokine during endotoxaemia, shock and multiple organ dysfunction syndromes. Plasma samples taken at presentation from 60 dogs with spontaneous acute pancreatitis of varying severity levels (scored 0-4 in ascending severity) were assessed for TNF activity by bioassay and total TNF protein levels through a dot-blot immunoassay. TNF activity by bioassay was detected in 31% (4/13) of dogs presenting with severe disease (>50% expected mortality) as defined using a scoring system for organ compromise, and was not detectable in the remaining animals or healthy controls. TNF activity was detected in 66% (4/6) animals in the highest severity group (Score 4), these animals were showing severe multiple organ dysfunction. Total TNF protein levels, measured by dot-blot immunoassay, exhibited a wide range in all severity groups and healthy dogs. Dogs with detectable TNF activity were not distinguished from the other severity or healthy groups by immunoassay. The absence of detectable differences in total TNF protein levels between the various severity groups suggests that other factors may be crucial in determining the role of TNF in spontaneous canine acute pancreatitis and subsequent endotoxaemia and shock.

A severity score for spontaneous canine acute pancreatitis.

OBJECTIVE: To derive a severity score for spontaneous canine acute pancreatitis applicable to general practice. DESIGN: Cohort study of canine pancreatitis cases. PROCEDURE: Cases (n = 68) of spontaneous canine acute pancreatitis presented to general practitioners were identified among accessions to Veterinary Pathology Services Brisbane. The primary veterinarian was surveyed by telephone to ascertain the outcome of each case. Scores were assigned for extent of hyperamylasaemia, hyperlipasaemia and number of organ systems other than the pancreas compromised. The probability of mortality with each score of each analyte was calculated. The strength of interaction between scores for each analyte and mortality rate was assessed by chi-square analysis where appropriate. Relationships between the organ system score, other physiological variables and likelihood of euthanasia were analysed. RESULTS: Scores derived mathematically from analysis of enzyme activities had poor abilities to predict mortality. The score based upon the number of organ systems compromised showed good ability to predict mortality and the interaction between the organ system score and mortality rate was significant by chi-square analysis (P < 0.01). Distribution of data within the amylase and lipase scores was not compatible with chi-square analysis. CONCLUSION: Assessment of severity of spontaneous canine acute pancreatitis using pancreatic enzyme activities is potentially inaccurate. The use of a severity score based upon organ system compromise was more accurate in determining the likelihood of mortality in spontaneous canine acute pancreatitis. This is compatible with the hypothesis that severe canine acute pancreatitis is a multiple organ failure syndrome.