Case report: Androgen-secreting adrenocortical tumors in eight cats.

Urine marking, aggression, and other behavioral concerns are common reasons for cat owners to seek veterinary care. Empiric treatment for lower urinary tract disease or primary behavior disorders are commonly pursued, especially in those cases with normal routine laboratory evaluations. Herein, we report the clinicopathologic findings in eight sexually altered cats that were diagnosed with androgen-secreting adrenocortical tumors. Nearly all cats (n = 7) initially were evaluated for inappropriate urination and pungent urine, with additional behavioral concerns including aggression (n = 3) and excess vocalization (n = 4) commonly reported. Penile barbs (n = 5) were identified in all five male cats, and an enlarged clitoris was observed in one female cat. Testing of serum androgen concentrations revealed abnormally high androstenedione (n = 1) or testosterone (n = 7) concentrations. In the five cases with available adrenal tissue, histopathologic evaluation identified either an adrenocortical adenoma (n = 3) or adrenocortical carcinoma (n = 2). Hormonal abnormalities resolved and clinical signs improved in the four cats that underwent surgical adrenalectomy, with each of these cats surviving >1 year. However, clinical signs were minimally impacted with medical treatments, including one cat in which trilostane treatment failed to improve clinical signs or testosterone concentrations. This collection of cases underscores the importance of a detailed physical examination as well as the consideration of endocrine disturbances in cats undergoing evaluation for inappropriate urination or aggression. Furthermore, this report adds to the growing body of evidence that sex-hormone secreting adrenal tumors in cats may be an under-recognized syndrome.

Urine electrolytes do not predict desoxycorticosterone pivalate efficacy in dogs with hypoadrenocorticism.

OBJECTIVE: To determine if urine electrolyte assessments can be used to monitor the adequacy of mineralocorticoid therapy in dogs with hypoadrenocorticism (HA). ANIMALS: 29 dogs with naturally occurring glucocorticoid- and mineralocorticoid-deficient HA. PROCEDURES: Urine sodium and potassium concentrations, sodium-to-potassium ratios, sodium-to-creatinine ratios, and potassium-to-creatinine (K:Cr) ratios were evaluated in dogs with newly diagnosed HA that were treated with desoxycorticosterone pivalate (DOCP). Dogs underwent measurements of urine and serum sodium, potassium, and creatinine concentrations and plasma renin activities twice monthly for up to 3 months. Regression analyses and calculation of coefficients of determination (R2) were performed to investigate potential associations between urine and serum variables. Urine variables also were compared between dogs considered to be undertreated or overtreated based on plasma renin activities. RESULTS: Urine K:Cr ratios were significantly associated with serum potassium concentrations 10 to 14 days (P = .002) and 30 days (P = .027) after the initial DOCP injection, but R2 values were only 0.35 and 0.17, respectively. Urine K:Cr ratios (median [IQR]) also were higher in dogs that were overtreated with DOCP (1.3 [0.7 to 2.3]) as compared to those dogs that were undertreated with DOCP (0.8 [0.5 to 0.9]) at 10 to 14 days after the initial DOCP injection (P = .039) but not at 30 days after the initial injection. Other urine variables were not significantly different between undertreated and overtreated dogs. CLINICAL RELEVANCE: Measures of urine electrolytes were not useful for assessing the adequacy of mineralocorticoid therapy in HA dogs that were treated with DOCP.

Clinical utility of an immunoglobulin A-based serological panel for the diagnosis of chronic enteropathy in dogs.

BACKGROUND: A panel of IgA-based serologic assays might aid in the diagnosis of chronic enteropathy (CE) in dogs, a syndrome encompassing conditions such as food-responsive enteropathy, immunosuppressant-responsive enteropathy, and inflammatory bowel disease (also referred to as chronic inflammatory enteropathy). However, it is unclear whether these biomarkers discriminate between CE and other types of primary intestinal disorders. OBJECTIVES: To evaluate a diagnostic panel that measures serum concentrations of IgA directed against OmpC (ACA), canine calprotectin (ACNA), and gliadin-derived peptides (AGA) in dogs with well-characterized intestinal diseases. ANIMALS: Fifty-five dogs with primary intestinal disease. METHODS: Serum ACA, ACNA, and AGA concentrations were measured in 30 dogs with CE and 25 dogs with other intestinal diseases (non-CE population), including histoplasmosis, parasitism, E. coli-associated granulomatous colitis, and lymphoma. Serum IgA concentrations were compared among populations, and sensitivities and specificities were calculated using laboratory-provided cut-points. RESULTS: Twenty-six of 30 (87%) CE dogs and 21 of 25 (84%) non-CE dogs had abnormal concentrations (intermediate or high) of at least 2 markers; these proportions were not significantly different (P = .99). A serum ACA concentration ≥15 EU/mL was 86.7% (95% confidence interval [CI], 69.3%-96.2%) sensitive and 24.0% (95% CI, 9.4%-45.1%) specific for CE diagnosis. High AGA concentrations were observed in 16 of 25 (64%) non-CE dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The evaluated serologic markers were poorly specific for CE diagnosis, which raises concerns that their use in clinical practice might lead to misdiagnoses and delayed or even detrimental treatments in dogs with non-CE intestinal diseases.

Relationship between serum magnesium, calcium, and parathyroid concentrations in dogs with abnormally low serum 25-hydroxyvitamin D concentration and chronic or protein-losing enteropathy.

BACKGROUND: The relationship between the development of SHPT and ionized magnesium (iMg) concentrations in blood of dogs with chronic gastrointestinal (GI) disease and abnormally low 25(OH)D is undefined. OBJECTIVES: Evaluate relationships between ionized magnesium (iMg), PTH, ionized calcium (iCa), and 25(OH)D in dogs with chronic enteropathy (CE) with or without protein-losing enteropathy (PLE) and abnormal 25(OH)D. Determine whether dogs with CE or PLE, decreased 25(OH)D and SHPT have differences in iMg, iCa, or 25(OH)D when compared to dogs that do not have SHPT. ANIMALS: Fifty dogs with CE +/- PLE and abnormally low serum 25(OH)D. METHODS: Retrospective search of submissions database at a veterinary diagnostic laboratory for vitamin D profiles submitted in years 2017 to 2020. Cases were excluded if supplemented with Ca, Mg, or vitamin D. Spearman correlation was performed to evaluate relationships between iMg, PTH, 25(OH)D, and iCa. Ionized Mg, iCa, and 25(OH)D concentrations were compared between dogs with SHPT and those with normal PTH concentrations. RESULTS: Concentrations of iMg were weakly negatively correlated with PTH (rho, -.31; P = .03), and weakly positively correlated with serum 25(OH)D (rho, .34, P = .02) and iCa (rho, .42, P = .003). Ionized magnesium concentrations were lower in dogs with abnormally low 25(OH)D and SHPT compared to dogs with abnormally low 25(OH)D and normal parathyroid hormone concentrations (P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Hypomagnesemia might contribute to alterations in iCa and parathyroid hormone in dogs with CE +/- PLE and abnormally low 25(OH)D.

Cardiovascular abnormalities in dogs with acute pancreatitis.

BACKGROUND: The prevalence and clinical importance of cardiac abnormalities in dogs with acute pancreatitis (AP) is unknown. ANIMALS: Twelve dogs with AP and 60 archived serum samples from dogs with suspected AP. METHODS: Two-phase study. PHASE I: Analysis of archived serum samples from dogs with clinical signs of AP and high Spec cPL concentrations. High sensitivity troponin I (TnIH) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were measured in achieved serum samples. PHASE II: Prospective observational study. Dogs with AP underwent echocardiography and Holter monitoring. Serum cardiac troponin I (cTnI) and plasma NT-proBNP concentrations were measured. Previously described disease severity indices were calculated for each dog. RESULTS: Phase I: 41 of 60 dogs suspected of having AP had abnormally high TnIH concentrations and 13 of 60 had abnormally high serum NT-proBNP concentrations. Higher TnIH concentrations were observed in dogs with Spec cPL concentration >2000 µg/L as compared to those with concentrations of 1000-2000 µg/L. PHASE II: 11 of 12 dogs diagnosed with pancreatitis had abnormal cTnI concentrations (median: 0.384 ng/mL, range: 0.041-2.966 ng/mL, RI: ≤0.06 ng/mL) and 7 of 12 dogs had plasma NT-proBNP concentrations above the reference interval (median: 971 pmol/L, range: 250-2215 pmol/L, RI: ≤900 pmol/L). Supraventricular and ventricular ectopic beats occurred in 3 dogs. Echocardiographic abnormalities were detected in 5 dogs. Cardiovascular variables were not associated with indices of disease severity. CONCLUSIONS AND CLINICAL IMPORTANCE: Myocardial injury is common in dogs with AP, but clinical consequences appeared to be uncommon in our small cohort. Cardiac biomarkers should be interpreted with caution in dogs with AP.

Peripheral biomarkers of oxidative stress in dogs with acute pancreatitis.

BACKGROUND: Oxidative stress is considered a pathomechanism of acute pancreatitis (AP), but no studies have extensively characterized oxidant status in dogs with naturally-occurring AP. HYPOTHESIS OR OBJECTIVES: Evaluate measures of oxidant status in dogs with AP and explore whether these measures correlate with AP severity. ANIMALS: Fifteen dogs with AP and 9 control dogs. METHODS: Prospective, controlled observational study. Plasma reactive metabolite (RM) concentrations, antioxidant potential (AOP), and urinary F2 isoprostane concentrations were measured in AP dogs and healthy controls. Severity of AP was assessed by length of hospitalization and 3 disease severity indices: canine acute pancreatitis severity (CAPS), modified canine activity index (M-CAI), and the acute patient physiologic and laboratory evaluation score (APPLEfull ). RESULTS: Reactive metabolite (RM) concentrations (median, 65 relative fluorescent units [RFU]/µL; range, 20-331 RFU/µL) and RM:AOP (median, 7; range, 4-109) were higher in AP dogs than healthy controls (median RM, 25 RFU/µL; range, 16-41 RFU/µL; median RM:AOP, 4; range, 2-7; P < .001 for both comparisons). Reactive metabolite (rS  = 0.603, P = .08) and RM:AOP (rS  = 0.491, P = .06) were not correlated with the duration of hospitalization or disease severity indices evaluated. However, disease severity indices did not predict mortality in our study. Normalized urine 2,3-dinor-8-iso-prostaglandin F2α concentrations were correlated with C-reactive protein (CRP; rS  = 0.491, P = .03), canine specific pancreatic lipase (Spec cPL; rS  = 0.746, P = .002), and CAPS (rS  = 0.603, P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Oxidant status is altered in dogs with naturally occurring AP, but the clinical relevance of this finding is unknown.

ATP7A, ATP7B, and RETN genotypes in Labrador Retrievers with and without copper-associated hepatopathy.

OBJECTIVE: To determine the frequency of previously reported coding variants in the ATP7A, ATP7B, and RETN genes in a US population of Labrador Retrievers and to explore potential associations of these genotypes with pathologic hepatic copper accumulation. SAMPLE: Archived hepatic specimens from 90 Labrador Retrievers collected between 2013 and 2021. PROCEDURES: The Michigan State University Veterinary Diagnostic Laboratory database was searched to identify archived tissues from Labrador Retrievers that had undergone hepatic histopathologic assessment. Cases were classified into control, copper-associated hepatopathy (CAH), and intermediate populations on the basis of histopathologic features and hepatic copper accumulation. The DNA was extracted from archived tissues and genotyped for reported variants in the 3 genes. Allele frequencies were determined, and associations of genotypes with CAH status were evaluated. RESULTS: 29 control dogs, 45 CAH dogs, and 16 intermediate dogs were included in the study. The overall ATP7A and RETN variant allele frequencies were 30% and 13%, respectively, and were not significantly different among control, CAH, and intermediate populations. The ATP7B variant allele frequency was significantly higher in the CAH population (30%) as compared to the control population (13%). However, 21 of 45 (47%) CAH dogs did not have an ATP7B variant allele whereas 7 of 28 (25%) control dogs did have an ATP7B variant allele. CLINICAL RELEVANCE: Study results supported a contributory role for the ATP7B variant in CAH pathogenesis in Labrador Retrievers. However, the application of genetic testing in a clinical setting is complicated by genotypic variability within healthy and diseased dogs.

Investigation of the urine cortisol to creatinine ratio for the diagnosis of hypoadrenocorticism in dogs.

OBJECTIVE: To evaluate the urine cortisol-to-creatinine ratio (UCCR) for the diagnosis of hypoadrenocorticism (HA) in dogs and to determine whether the method of urine cortisol measurement affects results. ANIMALS: 41 dogs with naturally occurring HA and 107 dogs with nonadrenal illness. PROCEDURES: Urine samples were prospectively collected from dogs undergoing testing for HA. Urine cortisol concentrations were measured at a veterinary diagnostic laboratory using either a radioimmunoassay (RIA) or a chemiluminescent immunoassay (CLIA). Receiver operating characteristic (ROC) curves were constructed to assess UCCR performance by both methods for HA diagnosis. Sensitivities, specificities, accuracies, and predictive values were calculated for various cutpoints. RESULTS: The areas under the ROC curves for UCCR diagnosis of HA were 0.99 (95% CI, 0.98 to 1.00) and 1.00 (95% CI, 1.00 to 1.00) when urine cortisol was determined by RIA and CLIA, respectively. An RIA UCCR of ≤ 2 was 97.2% sensitive, 93.6% specific, and 94.7% accurate for HA diagnosis, whereas a CLIA UCCR of ≤ 10 was 100% sensitive, specific, and accurate. An RIA UCCR > 4 and a CLIA UCCR of > 10 had negative predictive values of 100%. CLINICAL RELEVANCE: The UCCR was an accurate diagnostic test for HA in this study population, although equivocal results are possible. Case characteristics, method of cortisol measurement, and laboratory-specific cutpoints must be considered when interpreting results.

Localized alopecia and suppression of hypothalamic-pituitary-adrenal (HPA) axis in dogs following treatment with difluprednate 0.05% ophthalmic emulsion (Durezol®).

BACKGROUND: Despite the common use of topical ophthalmic corticosteroids in dogs, detailed reports on systemic and dermatologic adverse effects are limited. RESULTS: Nine purpose-bred research Beagles were treated with difluprednate 0.05% ophthalmic emulsion in one or both eyes 2-3 times daily. Some difluprednate treated dogs developed mild to severe alopecia of the periocular region, face, and distal pinna (5/9). The median duration of treatment prior to onset of dermatologic signs for difluprednate treated dogs was 550 days (453-1160 days). Diagnostic testing included complete blood count (CBC) and serum biochemistry, adrenocorticotropic hormone (ACTH) stimulation testing combined with endogenous ACTH measurement, and skin biopsy. The CBC and chemistry were within normal limits for all dogs. There were varying degrees of suppression of the hypothalamic-pituitary-adrenocortical (HPA) axis with difluprednate treatment. Dogs with the most profound alopecic changes had less pronounced HPA axis suppression compared to dogs with no integumentary changes. Skin biopsies demonstrated follicular atrophy and follicular keratosis. When topical difluprednate was reduced to unilateral therapy, the hair regrew on the untreated side of the face. In addition to the affected research dogs, a 7-year old female spayed Chihuahua that was being treated as a clinical patient with long-term difluprednate 0.05% ophthalmic emulsion developed generalized hypotrichosis on the head and body and a potbellied appearance. ACTH stimulation testing revealed suppression of the HPA axis with a mild increase in serum alkaline phosphatase (ALP) activity and a urine specific gravity of 1.016. The combination of clinical signs and laboratory abnormalities was supportive of iatrogenic hyperadrenocorticism. CONCLUSIONS: In dogs long-term use of difluprednate ophthalmic emulsion results in HPA axis suppression and in some cases iatrogenic hyperadrenocorticism. A novel pattern of localized alopecia is suspected to be related to dermal absorption and local action due to superior potency and penetration compared to other commonly utilized ophthalmic corticosteroids.

Evaluation of urine electrolytes for the diagnosis of hypoadrenocorticism in dogs.

BACKGROUND: Most dogs with primary hypoadrenocorticism (HA) have a mineralocorticoid deficiency, which decreases renal tubular sodium reabsorption and potassium excretion. Limited information is available concerning the clinical value of measuring urine electrolytes to aid in an HA diagnosis. OBJECTIVES: We aimed to evaluate the diagnostic utility of urine electrolyte measurements in dogs with HA. METHODS: Urine sodium and potassium concentrations were measured in 89 dogs, including 39 dogs with HA and 50 controls with nonadrenal illness. Fractional excretions of sodium (FENa ) and potassium (FEK ) were also calculated. Urine electrolytes and fractional excretion values were compared between the groups. Sensitivities and specificities were determined for various cut-points. RESULTS: The median urine sodium to potassium (Na:K) ratio was twofold greater (P < .001), and median FENa was fourfold greater (P < .001) in HA dogs as compared with controls. However, no cut-point for any variable with >90% sensitivity or specificity provided a corresponding specificity or sensitivity of >50%. When only dogs with abnormal serum or plasma electrolytes were included in the analyses, absolute urine electrolyte concentrations and FENa were not different between study populations (P > .05 for all comparisons), but the FEK was increased (P = .005) and the urine potassium:creatinine ratio was decreased (P < .001) in the control dogs compared with the dogs with HA. CONCLUSIONS: Urine electrolyte concentrations and fractional excretions are altered in dogs with HA. However, substantial overlap exists with control dogs with nonadrenal illness. Therefore, these values are unlikely to have diagnostic utility for dogs with HA.

Retrospective study of aldosterone and progesterone secreting adrenal tumors in 10 cats.

BACKGROUND: Primary hyperaldosteronism caused by adrenal neoplasia has been well described in cats. Multiple corticosteroid abnormalities occur in a subset of affected cats, but characterizations of this syndrome are limited to several case reports. OBJECTIVES: To describe a series of cats with adrenal tumors secreting aldosterone and additional corticosteroids. ANIMALS: Ten cats with multiple corticosteroid secreting adrenocortical tumors. METHODS: Retrospective case series. Medical records of cats with adrenal tumors secreting both aldosterone and progesterone were identified. Data concerning historical findings, clinicopathologic features, treatments, and outcomes were retrieved from medical records. RESULTS: All 10 cats had diabetes mellitus in addition to biochemical features of hyperaldosteronism such as hypokalemia. High corticosterone concentrations were observed in all 3 cats in which this corticosteroid was measured. Ultrasound examinations revealed unilateral adrenal tumors in all 10 cases, and the contralateral adrenal gland was either atrophied or not identified in 5 cats. Three of 4 cats developed hypoadrenocorticism after surgical adrenalectomy. Three cats achieved diabetic remission after adrenalectomy. Two cats treated with adrenalectomy survived >1 year, 1 cat survived 6.5 months, and 1 cat was alive 5.5 months after diagnosis. Survival >1 year occurred in 2 of 4 cats treated with medical management alone. Two cats were not treated. CONCLUSIONS AND CLINICAL IMPORTANCE: The presence of multiple corticosteroid abnormalities should be considered in cats with aldosterone secreting adrenal tumors, especially those with concurrent diabetes mellitus. Both surgical and medical management can result in long-term survival, although diabetic remission was documented only in cats undergoing adrenalectomy.

Assessment of iris vasculature abnormalities in dogs with diabetes mellitus.

OBJECTIVE: To identify and characterize abnormalities of iris vasculature in dogs with diabetes mellitus, compared to clinically normal, age-matched control dogs, by means of anterior segment angiography. ANIMALS: 10 dogs with naturally occurring diabetes mellitus and 10 age-matched control dogs with no ocular or systemic disease. PROCEDURES: The day before iris vasculature abnormality (IVA) assessment, all dogs underwent complete physical and ophthalmic examinations and baseline clinicopathologic analyses. For diabetic dogs, serum fructosamine concentration and a 12-hour blood glucose concentration curve were generated. The next day, all dogs were sedated and anterior segment angiography (following IV injection of indocyanine green [1 mg/kg] and subsequently sodium fluorescein [20 mg/kg]) was performed with a full-spectrum camera and camera adapter system. Group findings were compared, and multiple linear regression analysis was performed to identify potential factor associations with IVAs. RESULTS: During anterior segment angiography, the arterial, capillary, and venous phases were identified in all dogs. Times to onset of all phases in diabetic dogs were significantly less than those in control dogs. Vascular disruptions within the peripupillary region (evident following sodium fluorescein administration) were common in diabetic dogs. Severity of dye leakage into the iris stroma and aqueous humor was significantly greater in diabetic dogs than in control dogs. Duration of disease, mean blood glucose concentration, and serum fructosamine concentration were significantly associated with IVAs. CONCLUSIONS AND CLINICAL RELEVANCE: In diabetic dogs, anterior segment angiography revealed IVAs that were not evident in control dogs. The severity of those changes appeared to be associated with disease duration and blood glucose regulation.

Multiple corticosteroid abnormalities in cats with hyperaldosteronism.

BACKGROUND: The frequency with which multiple corticosteroid abnormalities occur in cats with aldosterone secreting adrenocortical tumors is unknown. OBJECTIVES: To evaluate adrenal-derived corticosteroids in cats in which blood samples were submitted for measure of aldosterone. ANIMALS: Two hundred ninety-seven cats. METHODS: Retrospective study. Analysis of a convenience sample of previously submitted serum or plasma. Progesterone, corticosterone, and cortisol were measured in feline serum or plasma samples submitted to an endocrinology laboratory for aldosterone measurements. Demographics and clinical history were retrieved from submittal forms when provided. Statistical testing was performed to investigate associations among the adrenal corticosteroids. RESULTS: Progesterone and corticosterone concentrations were strongly correlated (ρ = 0.74; P < .001). Progesterone (median, 5 nmol/L; interquartile range, 3-10 nmol/L) and corticosterone (113 nmol/L, 38-250 nmol/L) in cats with markedly increased aldosterone concentrations (≥3000 pmol/L) were higher than progesterone (1 nmol/L, 1-2 nmol/L) and corticosterone (12 nmol/L, 3-25 nmol/L) in cats with normal aldosterone concentrations (P < .001 for both comparisons). Progesterone concentrations ≥10 nmol/L (normal, ≤2 nmol//L) occurred in 24 of 76 (32%) cats with aldosterone concentrations ≥3000 pmol/L. Cortisol was lower in cats with aldosterone concentrations ≥3000 pmol/L as compared to those with aldosterone concentrations <500 pmol/L (59 nmol/L, 27-103 nmol/L vs 103 nmol/L, 49-182 nmol/L; P = .002). CONCLUSIONS AND CLINICAL IMPORTANCE: Multiple corticosteroid abnormalities occur in a subset of cats with hyperaldosteronism. The magnitude of increases in progesterone and corticosterone in some cats with hyperaldosteronism is likely to be clinically relevant.

Low-dose desoxycorticosterone pivalate treatment of hypoadrenocorticism in dogs: A randomized controlled clinical trial.

BACKGROUND: Desoxycorticosterone pivalate (DOCP) is a commonly used mineralocorticoid replacement for dogs with primary hypoadrenocorticism (HA), but manufacturer-recommended dosing protocols can be cost-prohibitive. Recent reports also have raised concerns that label dose protocols could be excessive. OBJECTIVE: To investigate the relative efficacy and adverse effects of 2 DOCP dosages in dogs with primary glucocorticoid and mineralocorticoid deficient HA. ANIMALS: Thirty-seven dogs, including 19 test population dogs and 18 controls. METHODS: Randomized controlled double-blinded clinical trial. Dogs with newly diagnosed primary HA were assigned to standard (2.2 mg/kg q30d, control population) or low-dose (1.1 mg/kg q30d, test population) DOCP treatment. Clinical and laboratory variables were assessed 10 to 14 days and approximately 30 days after each DOCP treatment for 90 days. RESULTS: Mean serum sodium to potassium ratios at reevaluations were ≥32 in both populations throughout the study. No dog developed electrolyte abnormalities warranting medical treatment, although hypokalemia occurred on at least 1 occasion in 9 controls and 6 test population dogs. Urine specific gravities (median, interquartile range) were lower in control dogs (1.022, 1.016-1.029) as compared to test population dogs (1.033, 1.023-1.039; P = .006). Plasma renin activity was overly suppressed on 84 of 104 (80.8%) assessments in control dogs whereas increased renin activity occurred on 23 of 112 (20.5%) assessments in test population dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose DOCP protocols appear to be safe and effective for treatment of HA in most dogs. Standard-dose protocols are more likely to result in biochemical evidence of overtreatment.

Association between biliary tree manipulation and outcome in dogs undergoing cholecystectomy for gallbladder mucocele: A multi-institutional retrospective study.

OBJECTIVE: To determine whether catheterization of the common bile duct (CBD) is associated with outcome in dogs undergoing cholecystectomy for gallbladder mucocele and to determine whether this association is modified by the catheterization method. STUDY DESIGN: Multi-institutional retrospective cohort study. ANIMALS: Dogs (n = 252) that underwent cholecystectomy for gallbladder mucocele. METHODS: Dogs were identified via electronic medical record review at four veterinary teaching hospitals. Baseline dog characteristics, surgical findings, and methods including normograde vs retrograde CBD catheterization, intraoperative outcomes, and postoperative outcomes and complications were recorded. Variables were compared between dogs with and without catheterization. RESULTS: Catheterized dogs had higher American Society of Anesthesiologists scores (P = .04), higher total bilirubin (P = .01), and were more likely to have dilated CBD at the time of surgery (P < .01). Incidence of major and minor intraoperative complications was similar between the two groups. Surgical time was longer for the catheterized group (P = .01). The overall incidence of postoperative complications was similar between the groups; however, postoperative pancreatitis was associated with performing CBD catheterization (P = .01). This association was retained as an independent association in a multivariable model that addressed baseline group differences (P = .04). Likelihood of developing postoperative pancreatitis was not different between normograde and retrograde catheterization (P = .57). CONCLUSION: Catheterization of the CBD was associated with development of postoperative pancreatitis. This was not influenced by the method of catheterization. CLINICAL SIGNIFICANCE: The requirement for catheterization of the CBD during open cholecystectomy in dogs should be carefully considered, particularly in dogs without evidence of biliary obstruction because the procedure may induce postoperative pancreatitis.

Liquid chromatography/tandem mass spectrometric analysis of penicillamine for its pharmacokinetic evaluation in dogs.

Copper storage disease occurs in multiple dog breeds and is one of the most common causes of chronic hepatitis in this species. The disease is caused by hereditary defects in copper metabolism in conjunction with high dietary copper levels. The progressive copper accumulation leads to hepatitis, cirrhosis, and eventually death if left untreated. Copper chelators are critical in modulating the effects of this disease. It is therefore of significant practicality to understand the pharmacokinetic (PK) parameters of chelating agents, particularly since they are oftentimes quite expensive. A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed to measure plasma levels of one of the most common chelators, d-penicillamine. The compound was discovered to exist in two forms, monomeric and dimeric, and various chemical derivatizations were tried to force the compound into one form or the other. Eventually, the simplest approach was individual determination of penicillamine and its dimer, with summation of the two quantities. This enabled determination of canine PK parameters for penicillamine based on comparison of oral and intravenous administration of the drug, including time to maximum drug level (Tmax), concentration at maximum (Cmax), clearance (Cls) and volume of distribution (Vdss). The drug was found to exist predominantly in the dimeric form in plasma, which is incapable of chelating copper owing to lack of free sulfhydryl groups and must therefore provide a storage form of the drug in equilibrium with its monomeric form in vivo. Mechanisms are discussed for the electrospray-induced fragmentation of penicillamine as well as of its dimer.

Metronidazole treatment of acute diarrhea in dogs: A randomized double blinded placebo-controlled clinical trial.

BACKGROUND: Metronidazole is commonly administered to dogs with acute diarrhea, but there is limited evidence to support this practice. OBJECTIVE: To investigate the effects of metronidazole administration on dogs with acute nonspecific diarrhea. ANIMALS: Thirty-one dogs, including 14 test population dogs and 17 controls. METHODS: Randomized controlled clinical trial. Dogs with acute diarrhea in which causation was not determined by routine fecal diagnostic testing were randomly assigned to metronidazole treatment (10-15 mg/kg PO q12h for 7 days) or placebo. Fecal cultures and characterization of Clostridium perfringens isolates also were performed. Owners maintained medication and fecal scoring logs, and fecal diagnostic tests were repeated on day 7. RESULTS: The mean ± SD time to resolution of diarrhea for test population dogs (2.1 ± 1.6 days) was less than that for controls (3.6 ± 2.1 days, P = .04). Potential relationships of C. perfringens with acute diarrhea pathogenesis were not investigated, but only 3 of 13 (23.1%) test population dogs had persistent C. perfringens carriage at day 7, which was less than the 11 of 14 (78.6%) controls with persistent growth (P = .007). CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that metronidazole treatment can shorten duration of diarrhea and decrease fecal culture detection of C. perfringens in some dogs with acute nonspecific diarrhea. Additional studies are needed to assess the benefits and risks of routine use of metronidazole for this purpose because most dogs achieve resolution of diarrhea within several days regardless of treatment.

Prevalence, distribution, and risk factors for canine blastomycosis in Michigan, USA.

Blastomycosis is a systemic fungal infection that most commonly affects dogs and humans. The disease is thought to be endemic in southern regions of Michigan, USA, but epidemiologic investigations have not been reported in detail for this state. The primary aims of this study were to investigate the prevalence and distribution of canine blastomycosis cases in Michigan and to identify risk factors for infection. Over 200 primary care veterinary clinics throughout the state were surveyed regarding blastomycosis prevalence, and demographic information was obtained from medical records of affected dogs that were evaluated at these clinics. A retrospective case control study was conducted for an additional 49 dogs with blastomycosis that were evaluated at specialty referral centers located in the southern mid-Michigan region. Prevalence rates were calculated for each county, and cases were mapped using geocoding software. Univariable and multivariable analyses were used to identify risk factors for infection. Prevalence rates were ≥100 cases per 100,000 dogs in five counties. Most blastomycosis cases originated from the Upper Peninsula or from a high-density area in the northern Lower Peninsula. Multivariable regression analysis identified travel or residence north of the 45th parallel as a strong risk factor for infection (P < .001). Blastomycosis was uncommon in southern counties. These results refute previous speculations and should be of value to both human and animal health. Given that many heightened risk areas are popular tourist destinations, practitioners across the USA should be mindful of the spatial distribution of blastomycosis in Michigan.