Evaluation of Aldosterone Concentrations in Dogs with Hypoadrenocorticism

Background

Some dogs with primary hypoadrenocorticism (HA) have normal sodium and potassium concentrations, a phenomenon called atypical Addison''s disease. The assumption that the zona glomerulosa and aldosterone secretion in these dogs are normal seems widely accepted; however, aldosterone measurements are missing in most published cases.

Objectives

To measure aldosterone in dogs with HA with and without electrolyte abnormalities and to determine the time point of aldosterone peak concentrations during ACTH stimulation.

Animals

Seventy dogs with HA, 22 dogs with diseases mimicking HA, and 19 healthy dogs.

Methods

Prospective study. Blood samples were taken before and 60 minutes after injection of 250 μg ACTH in all dogs. Additional blood samples were taken 15, 30, and 45 minutes after ACTH in 7 dogs with HA and in 22 with diseases mimicking HA.

Results

Baseline and ACTH‐stimulated aldosterone was significantly lower in dogs with HA than in the other groups. Aldosterone was low or undetectable in 67/70 dogs with HA independently of sodium and potassium levels. In 3 dogs, sodium/potassium concentrations were normal; in 1 dog, sodium was normal and potassium decreased. In all 4, ACTH‐stimulated aldosterone concentrations were below the detection limit of the assay. Aldosterone concentrations were not different at 30, 45, or 60 minutes after ACTH administration.

Conclusion and Clinical Importance

Cortisol and aldosterone secretion is compromised in dogs with HA with and without electrolyte abnormalities. The term atypical Addison''s disease, used for dogs with primary HA and normal electrolytes, must be reconsidered; other mechanisms allowing normal electrolyte balance without aldosterone should be evaluated in these dogs.     

Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH

Background

The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice.

Objectives

The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs.

Animals

Twenty‐two healthy dogs, 10 dogs with suspected hypoadrenocorticism (HA) and 15 dogs with suspected hyperadrenocorticism (HC).

Methods

Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 μg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation.

Results

Peak cortisol concentrations were reached after 2–4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 μg/dL in all healthy dogs and >5 μg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol‐increase above the detection‐limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours.

Conclusions and Clinical Importance

The depot formulation can be used in place of the short‐acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA‐suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time.     

Cortisol Concentrations in Well‐Regulated Dogs with Hyperadrenocorticism Treated with Trilostane

Background

There are no clear treatment guidelines for dogs with clinically well‐regulated hyperadrenocorticism in which serum cortisol concentrations before and after an ACTH stimulation test performed 3–6 hours after trilostane administration are < 2.0 μg/dL.

Objective

To determine if serum cortisol concentrations measured before (Pre1) and after (Post1) ACTH stimulation at 3–6 hours after trilostane administration are significantly lower than cortisol concentrations measured before (Pre2) and after (Post2) ACTH stimulation 9–12 hours after trilostane administration, in a specific population of dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 <2 μg/dL.

Animals

Thirteen client‐owned dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 serum cortisol concentrations <2.0 μg/dL 3–6 hours after trilostane administration.

Methods

Prospective study. Dogs had a second ACTH stimulation test performed 9–12 hours after trilostane administration, on the same day of the first ACTH stimulation test. Cortisol concentrations before and after ACTH stimulation were compared using a paired t‐test.

Results

Cortisol concentrations before (1.4 ± 0.3 μg/dL) and after the first stimulation (1.5 ± 0.3 μg/dL, mean ± SD) were significantly lower than cortisol concentration before the second stimulation (3.3 ± 1.6 μg/dL, P = .0012 each). Cortisol concentration before the first stimulation was also significantly lower than cortisol concentration after the second stimulation (5.3 ± 2.4 μg/dL, P = .0001).

Conclusions and clinical importance

In dogs with clinically well‐regulated, trilostane‐treated, hyperadrenocorticism, and cortisol concentrations <2 μg/dL before and after the first stimulation, a second ACTH stimulation test performed 9–12 hours after treatment can result in higher cortisol concentrations that could support continued trilostane treatment.     

Serial Evaluation of Abdominal Fluid and Serum Amino‐terminal pro‐C‐type Natriuretic Peptide in Dogs with Septic Peritonitis

Background

Serum N‐terminal pro‐C‐natriuretic peptide (NT‐proCNP) has shown promise as a diagnostic biomarker for sepsis. Its sensitivity to detect dogs with septic peritonitis (SP) is reportedly low, perhaps attributable to the compartmentalization of NT‐proCNP in the abdominal cavity.

Objectives

To evaluate the use of an ELISA for the measurement of NT‐proCNP in canine abdominal fluid and to describe the peri‐operative pattern of abdominal fluid and serum NT‐proCNP concentrations in dogs with SP.

Animals

Five client‐owned dogs with nonseptic abdominal effusion of varying etiologies and 12 client‐owned dogs with SP undergoing abdominal surgery and placement of a closed‐suction abdominal drain (CSAD). Six dogs were included upon hospital admission; 6 were included the day after surgery.

Methods

Prospective pilot study. A commercially available ELISA kit was analytically validated for use on canine abdominal fluid. The NT‐proCNP concentrations were measured in the abdominal fluid of control dogs, and in serum and abdominal fluid of dogs with SP from admission for CSAD removal.

Results

In dogs with SP, admission abdominal fluid NT‐proCNP concentrations were lower than the concurrent serum concentrations (P = 0.031), and lower than control canine abdominal fluid concentrations (P = 0.015). Postoperatively, abdominal fluid NT‐proCNP concentrations remained lower than serum concentrations (P < 0.050), except on day 4.

Conclusions and Clinical Importance

The ELISA kit was able to measure NT‐proCNP in canine abdominal fluid. In dogs with SP, low serum NT‐proCNP concentrations cannot be explained by abdominal compartmentalization.     

Use of the Cortisol‐to‐ACTH Ratio for Diagnosis of Primary Hypoadrenocorticism in Dogs

Background

The ACTH stimulation test is currently required for definitive diagnosis of hypoadrenocorticism. Increased cost of synthetic ACTH (cosyntropin) has prompted a search for alternative diagnostic methods.

Objective

The purpose of this study was to determine whether a cortisol‐to‐ACTH ratio (CAR) can be used to differentiate dogs with hypoadrenocorticism from normal dogs and those with nonadrenal illness.

Animals

Eight healthy dogs (H), 19 dogs with nonadrenal illness (NAI), and 15 dogs with hypoadrenocorticism (HAD).

Methods

Dogs in the HAD group were retrospectively identified from PUVTH medical records. The NAI group consisted of hospitalized dogs with clinical signs, clinicopathologic findings, or both, consistent with a diagnosis of hypoadrenocorticism, but in which hypoadrenocorticism was ruled out based on ACTH stimulation test results. Healthy dogs were recruited from hospital staff and students. Endogenous ACTH concentrations and cortisol concentrations before and after ACTH stimulation were measured in all dogs.

Results

Baseline cortisol concentration was significantly lower, and ACTH concentration was significantly higher, in the HAD group versus the H and NAI group (P < .001). However, there was overlap among groups. Cortisol‐to‐ACTH ratio was significantly lower in the HAD group versus the H and NAI groups (P < .001), and there was no overlap between the HAD group and the other 2 groups.

Conclusions and Clinical Importance

CAR can be used for definitive diagnosis of primary hypoadrenocorticism.     

Co‐infections with Respiratory Viruses in Dogs with Bacterial Pneumonia

Background

Bacterial pneumonia (BP) is an inflammation of the lower airways and lung parenchyma secondary to bacterial infection. The pathogenesis of BP in dogs is complex and the role of canine respiratory viruses has not been fully evaluated.

Objectives

The aim of this study was to investigate the occurrence of viral co‐infections in dogs with BP and to assess demographic or clinical variables as well as disease severity associated with viral co‐infections.

Animals

Twenty household dogs with BP caused by opportunistic bacteria and 13 dogs with chronic (>30 days) tracheobronchitis caused by Bordetella bronchiseptica (BBTB).

Methods

Prospective cross‐sectional observational study. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and cytologic and microbiologic analysis of bronchoalveolar lavage or transtracheal wash fluid. Canine parainfluenza virus (CPIV), canine adenovirus, canine herpes virus, canine influenzavirus, canine distemper virus, canine respiratory coronavirus (CRCoV) and canine pneumovirus, as well as B. bronchiseptica and Mycoplasma spp. were analyzed in respiratory samples using PCR assays.

Results

CPIV was detected in 7/20 and CRCoV in 1/20 dogs with BP. Respiratory viruses were not detected in dogs with BBTB. There were no significant differences in clinical variables between BP dogs with and without a viral co‐infection.

Conclusion and Clinical Importance

Respiratory viruses were found frequently in dogs with BP and may therefore play an important role in the etiology and pathogenesis of BP. Clinical variables and disease severity did not differ between BP dogs with and without viral co‐infection.     

Quantitative Contrast‐enhanced Ultrasonographic Assessment of Naturally Occurring Pancreatitis in Dogs

Background

Quantitative contrast‐enhanced ultrasonography (CEUS) can detect pancreatic perfusion changes in experimentally induced canine pancreatitis. However, its usefulness in detecting perfusion changes in naturally occurring pancreatitis is unclear.

Hypothesis/Objectives

To determine the feasibility of using CEUS to detect pancreatic and duodenal perfusion changes in naturally occurring canine pancreatitis.

Animals

Twenty‐three client‐owned dogs with pancreatitis, 12 healthy control dogs.

Methods

Dogs diagnosed with pancreatitis were prospectively included. CEUS of the pancreas and duodenum were performed. Time‐intensity curves were created from regions of interest in the pancreas and duodenum. Five perfusion parameters were obtained for statistical analyses: time to initial up‐slope, peak time (Tp), time to wash‐out (TTW), peak intensity (PI), and area under the curve (AUC).

Results

For the pancreas, Tp of the pancreatitis group was prolonged when compared to controls (62 ± 11 seconds versus 39 ± 13 seconds; P < .001). TTW also was prolonged but not significantly (268 ± 69 seconds versus 228 ± 47 seconds; P = .47). PI and AUC were increased when compared to controls (95 ± 15 versus 78 ± 13 MPV; P = .009 and 14,900 ± 3,400 versus 11,000 ± 2,800 MPV*s; P = .013, respectively). For the duodenum, PI and AUC were significantly increased in the pancreatitis group when compared to controls.

Conclusions and Clinical Importance

Contrast‐enhanced ultrasonography can detect pancreatic perfusion changes in naturally occurring canine pancreatitis characterized by delayed peak with prolonged hyperechoic enhancement of the pancreas on CEUS. Additionally, duodenal perfusion changes secondary to pancreatitis were observed.     

Pulmonary Vein‐to‐Pulmonary Artery Ratio is an Echocardiographic Index of Congestive Heart Failure in Dogs with Degenerative Mitral Valve Disease

Background

Early recognition of left‐sided congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD) is important because it influences medical therapy, timing of follow‐up, and outcome.

Hypothesis

Pulmonary vein diameter‐to‐pulmonary artery diameter ratio (PV/PA) measured by echocardiography can predict CHF.

Animals

Ninety‐eight client‐owned dogs, 37 controls, and 61 dogs with DMVD.

Methods

Prospective clinical cohort study. History, physical examination and Doppler‐echocardiography were performed. Dogs were classified as International Small Animal Cardiac Health Council class I, II or III. Congestive heart failure was identified in a subset of 56 dogs based on radiographic findings. The PV/PA was measured in bidimensional (2D) and M‐mode by 2 investigators blinded to the radiologists’ conclusions.

Results

Interobserver coefficients of variation for PV/PA acquisition and measurement were <10%. The PV/PA in control dogs was approximately 1 and increased with class of heart failure. The presence of CHF could be best predicted by measuring PV/PA in 2D echocardiography (cut‐off, 1.7; area under the curve, 0.98; CI, 0.97–0.98; P < .001) with a sensitivity of 96% and a specificity of 91%.

Conclusion and clinical importance

The PV/PA is a simple and reproducible echocardiographic variable that increases with class of heart failure and may help discriminate dogs in CHF from asymptomatic dogs with DMVD. Additional studies are required to determine whether PV/PA might provide additional information in the integrated interpretation of Doppler‐echocardiographic indices of left ventricular filling pressures and could be used for rapid assessment of CHF in dogs in a critical care setting.     

Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Background

Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.

Hypothesis/Objectives

The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse‐administered toceranib phosphate (TOC) combined with lomustine.

Animals

Forty‐seven client‐owned dogs with measurable MCT.

Methods

Toceranib phosphate was given PO on days 1, 3 and 5 of a 21‐day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m². All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.

Results

The MTD of lomustine was established at 50 mg/m² when combined with pulse‐administered TOC; the dose‐limiting toxicity was neutropenia. Forty‐one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression‐free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.

Conclusions and clinical importance

Combined treatment with pulse‐administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.     

The Prognostic Value of Perioperative Profiles of ACTH and Cortisol for Recurrence after Transsphenoidal Hypophysectomy in Dogs with Corticotroph Adenomas

Background

Transsphenoidal hypophysectomy is an effective treatment for dogs with pituitary‐dependent hypercortisolism (PDH). However, long‐term recurrence of hypercortisolism is a well‐recognized problem, indicating the need for reliable prognostic indicators.

Objectives

The aim of this study was to evaluate the prognostic value of perioperative plasma ACTH and cortisol concentrations for identifying recurrence of hypercortisolism after transsphenoidal hypophysectomy.

Animals

A total of 112 dogs with PDH that underwent transsphenoidal hypophysectomy met the inclusion criteria of the study.

Methods

Hormone concentrations were measured preoperatively and 1–5 hours after surgery. Both absolute hormone concentrations and postoperative concentrations normalized to preoperative concentrations were included in analyses. The prognostic value of hormone concentrations was studied with Cox''s proportional hazard analysis.

Results

Median follow‐up and disease‐free period were 1096 days and 896 days, respectively. Twenty‐eight percent of patients had recurrence, with a median disease‐free period of 588 days. Both absolute and normalized postoperative cortisol concentrations were significantly higher in dogs with recurrence than in dogs without recurrence. High ACTH 5 hours after surgery, high cortisol 1 and 4 hours after surgery, high normalized ACTH 3 hours after surgery, high normalized cortisol 4 hours after surgery and the random slope of cortisol were associated with a shorter disease‐free period.

Conclusions and clinical importance

Individual perioperative hormone curves provide valuable information about the risk of recurrence after hypophysectomy. However, because no single cutoff point could be identified, combination with other variables, such as the pituitary height/brain area (P/B) ratio, is still needed to obtain a good estimate of the risk for recurrence of hypercortisolism after hypophysectomy.     

Incidence,Timing, and Risk Factors of Azathioprine Hepatotoxicosis in Dogs

Background

The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias.

Hypothesis and Objectives

To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias.

Animals

Fifty‐two dogs treated with AZA with clinical and biochemical follow‐up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum.

Methods

Retrospective medical record review, from January 2009 through December 2013.

Results

Hepatotoxicosis (as defined by a >2‐fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13–22 days). Dogs had a median 9‐fold increase in ALT and 8‐fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over‐represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow‐up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45–196 days) compared to hepatotoxicosis (P = .016).

Conclusions and Clinical Importance

These results support the routine monitoring of liver enzymes during the first 1–4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.     

An Open‐label Phase 1 Dose‐escalation Clinical Trial of a Single Intravenous Administration of Gemcitabine in Dogs with Advanced Solid Tumors

Background

A broad range of gemcitabine dosages have been used in dogs.

Hypothesis/Objectives

To determine maximally tolerated dose (MTD), dose‐limiting toxicity (DLT), and preliminary antitumor activity of intravenous administration of gemcitabine in dogs with advanced solid tumors.

Animals

Twenty‐two client‐owned dogs.

Methods

Dogs with advanced cancer were prospectively enrolled in an open‐label Phase 1 study of gemcitabine. Gemcitabine was administered as a 30‐minute intravenous bolus starting at 800 mg/m², using escalation of 50 mg/m² increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Treatment continued until disease progression or unacceptable toxicosis. Additional dogs were enrolled at MTD to better characterize tolerability, and to assess the extent and duration of gemcitabine excretion.

Results

Twenty‐two dogs were treated at 4 dose levels, ranging from 800 to 950 mg/m². Neutropenia was identified as DLT. MTD was 900 mg/m². DLT consisting of grade 4 febrile neutropenia was observed at 950 mg/m² in 2 dogs. There were no nonhematologic DLTs. Twenty dogs received multiple doses, and none had evidence of severe toxicosis from any of their subsequent treatments. At 900 mg/m², 2 complete and 5 partial responses were observed in dogs with measurable tumors. The amount of gemcitabine excreted in urine decreased over time, and was undetectable after the first 24 hours.

Conclusions and Clinical Importance

The recommended dose of gemcitabine for future Phase 2 studies is weekly 900 mg/m². In chemotherapy‐naïve dogs with advanced solid tumor this dose level merits further evaluation.     

Procoagulant Microparticles in Dogs with Immune‐Mediated Hemolytic Anemia

Background

Studies of some human prothrombotic diseases suggest that phosphatidylserine‐positive (PS+) and tissue factor‐positive (TF+) microparticles (MPs) might play a role in the pathogenesis of thrombosis or serve as biomarkers of thrombotic risk.

Hypothesis/Objectives

To determine if circulating levels of PS+MP and procoagulant activity (PCA) associated with PS+MPs and TF+ MPs are increased in dogs with IMHA.

Animals

Fifteen dogs with primary or secondary IMHA and 17 clinically healthy dogs.

Methods

Prospective case‐controlled observational study. Circulating PS+MPs were measured by flow cytometry. PCA associated with PS+MPs and TF+MPs was measured by thrombin and Factor Xa generating assays, respectively.

Results

Circulating numbers of PS+MPs were not significantly higher in dogs with IMHA [control median 251,000/μL (36,992–1,141,250/μL); IMHA median 361,990/μL (21,766–47,650,600/μL) P = .30]. However, PS+MP PCA [control median 2.2 (0.0–16.8) nM PS eq; IMHA median 8.596, (0–49.33 nM PS eq) P = .01] and TF+MP PCA [control median 0.0, (0.0–0.0 pg/mL); IMHA median 0.0; (0–22.34 pg/mL], P = .04) were increased. Intravascular hemolysis, which we showed might increase PS+ and TF+MP PCA, was evident in 3 of 5 dogs with PS+MP PCA and 2 of 4 dogs with TF+MP PCA higher than controls. Underlying disease in addition to IMHA was detected in 1 of 5 dogs with PS+PCA and 3 of 4 dogs with TF+MP PCA higher than controls.

Conclusions and Clinical Importance

TF+ and PS+MP PCA is increased in some dogs with IMHA. Further studies that determine if measuring TF+ and PS+ MP PCA can help identify dogs at risk for thrombosis are warranted.     

Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case‐Control Study

Background

The cause of gallbladder mucocele (GBM) formation in dogs currently is unknown. Many available drugs represent a newer generation of xenobiotics that may predispose dogs to GBM formation.

Objective

To determine if there is an association between the histologic diagnosis of GBM in dogs and administration of selected drugs.

Animals

Eighty‐one dogs with a histologic diagnosis of GBM and 162 breed, age, and admission date‐matched control dogs from a single referral institution.

Methods

Medical records of dogs with GBM and control dogs from 2001 to 2011 were reviewed. Owner verification of drug history was sought by a standard questionnaire. Reported use of heartworm, flea, and tick preventatives as well as nonsteroidal anti‐inflammatory drugs, analgesics, corticosteroids, or medications for treatment of osteoarthritis was recorded.

Results

Dogs with GBM were 2.2 times as likely to have had reported use of thyroxine (as a proxy for the diagnosis of hypothyroidism) as control dogs (95% confidence interval [CI], 0.949–5.051), 3.6 times as likely to have had reported treatment for Cushing''s disease (95% CI, 1.228–10.612), and 2.3 times as likely to have had reported use of products containing imidacloprid (95% CI, 1.094–4.723). Analysis of a data subset containing only Shetland sheepdogs (23 GBM and 46 control) indicated that Shetland sheepdogs with GBM formation were 9.3 times as likely to have had reported use of imidacloprid as were control Shetland sheepdogs (95% CI, 1.103–78.239).

Conclusions and Clinical Importance

This study provides evidence for an association between selected drug use and GBM formation in dogs. A larger epidemiologic study of Shetland sheepdogs with GBM formation and exposure to imidacloprid is warranted.     

Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy

Background

Dogs with a chronic enteropathy (CE) have a lower vitamin D status, than do healthy dogs. Vitamin D status has been associated with a negative clinical outcome in humans with inflammatory bowel disease.

Objectives

To examine the relationship between serum 25 hydroxyvitamin D (25(OH)D) concentrations at diagnosis and clinical outcome in dogs with a CE.

Animals

Forty‐one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary Studies, Hospital for Small Animals between 2007 and 2013.

Methods

Retrospective review. Serum 25(OH)D concentrations were compared between dogs which were alive at follow up or had died because of non‐CE‐related reasons (survivors) and dogs which died or were euthanized due to their CE (non‐survivors). A binary logistic regression analysis was performed to determine significant predictors of death in dogs with CE.

Results

Serum concentrations of 25(OH)D at the time a CE was diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors 4.36 ng/mL, interquartile range 1.6–17.0 ng/mL), median survivors (n = 26) (24.9 ng/mL interquartile range 15.63–39.45 ng/mL, P < .001). Serum 25(OH)D concentration was a significant predictor of death in dogs with CE (odds ratio 1.08 [95% CI 1.02–1.18)]).

Conclusions

Serum 25(OH)D concentrations at diagnosis are predictive of outcome in dogs with CE. The role of vitamin D in the initiation and outcome of chronic enteropathies in dogs is deserving of further study.     

Atlanto‐Axial Malformation and Instability in Dogs with Pituitary Dwarfism due to an LHX3 Mutation

Background

Canine pituitary dwarfism or combined pituitary hormone deficiency (CPHD) in shepherd dogs is associated with an LHX3 mutation and can lead to a wide range of clinical manifestations. Some dogs with CPHD have neurological signs that are localized to the cervical spine. In human CPHD, caused by an LHX3 mutation, anatomical abnormalities in the atlanto‐axial (C1‐C2) joint have been described.

Objectives

To evaluate the presence of atlanto‐axial malformations in dogs with pituitary dwarfism associated with an LHX3 mutation and to investigate the degree of similarity between the atlanto‐axial anomalies found in canine and human CPHD patients with an LHX3 mutation.

Animals

Three client‐owned Czechoslovakian wolfdogs and 1 client‐owned German shepherd dog, previously diagnosed with pituitary dwarfism caused by an LHX3 mutation, with neurological signs indicating a cervical spinal disorder.

Methods

Radiography, computed tomography, and magnetic resonance imaging of the cranial neck and skull, necropsy, and histology.

Results

Diagnostic imaging identified abnormal positioning of the dens axis and incomplete ossification of the suture lines between the ossification centers of the atlas with concurrent atlanto‐axial instability and dynamic compression of the spinal cord by the dens axis. The malformations and aberrant motion at C1–C2 were confirmed at necropsy and histology.

Conclusions and Clinical Importance

The atlanto‐axial abnormalities of the dwarf dogs resemble those encountered in human CPHD patients with an LHX3 mutation. These findings suggest an association between the LHX3 mutation in dogs with CPHD and atlanto‐axial malformations. Consequently, pituitary dwarfs should be monitored closely for neurological signs.     

Vitamin D Status in Different Stages of Disease Severity in Dogs with Chronic Valvular Heart Disease

Background

In humans with heart disease, vitamin D deficiency is associated with disease progression and a poor prognosis. A recent study showed that serum 25‐hydroxyvitamin D [25(OH)D] concentration, the hallmark of vitamin D status, was lower in dogs with heart failure than in normal dogs, and a low concentration was associated with poor outcome in dogs with heart failure.

Objectives

To elucidate the vitamin D status of dogs with chronic valvular heart disease (CVHD) at different stages of disease severity.

Animals

Forty‐three client‐owned dogs with CVHD.

Methods

In this cross‐sectional study, dogs were divided into 3 groups (14 dogs in Stage B1, 17 dogs in Stage B2, and 12 dogs in Stage C/D) according to ACVIM guidelines. Dogs underwent clinical examination including echocardiography. Serum 25(OH)D concentrations were measured in each dog.

Results

Serum 25(OH)D concentration was significantly lower in Stage B2 (median, 33.2 nmol/L; range, 4.9–171.7 nmol/L) and C/D (13.1 nmol/L; 4.9–58.1 nmol/L) than in Stage B1 (52.5 nmol/L; 33.5–178.0 nmol/L) and was not significantly different between Stage B2 and Stage C/D. Among clinical variables, there were significant negative correlations between 25(OH)D concentration and both left atrial‐to‐aortic root ratio and left ventricular end‐diastolic diameter normalized for body weight.

Conclusions and Clinical Importance

These results indicate that vitamin D status is associated with the degree of cardiac remodeling, and the serum 25(OH)D concentration begins to decrease before the onset of heart failure in dogs with CVHD.     

Plasma Vitamin D Metabolites and C‐Reactive Protein in Stage‐Stop Racing Endurance Sled Dogs

Background

Dogs are a unique model for examining the effects of exercise on vitamin D status because of their lack of vitamin D synthesis by UV exposure. In addition, the inflammatory response may be associated with hypovitaminosis D.

Objectives

To investigate the effects of several days of endurance exercise on plasma vitamin D (25‐(OH)D₃, 24,25‐(OH)D₃ and 1,25(OH)D₃) and serum C‐reactive protein (CRP) concentrations in stage‐stop racing sled dogs.

Animals

12 racing sled dogs and 8 control dogs.

Methods

Blood was collected before the race and immediately after racing on days 2 and 8. Plasma vitamin D metabolites and serum CRP concentrations were measured.

Results

Racing dogs showed a significant increase in 25(OH)D₃ on day 2 (P = .027) and day 8 of the race (P < .001), whereas no increases were observed in control dogs. The plasma concentration of 24,25(OH)D₃ showed a significant increase by day 8 (P < .001). There were no significant changes in 1,25(OH) D₃ concentrations across all time points and groups. Racing dogs had significantly increased CRP concentrations by day 2 (39.3 ± 30.1 μg/mL; P < .001).

Conclusions and Clinical Importance

Increases in vitamin D metabolites as well as increases in CRP concentrations were observed in racing sled dogs. This finding was contrary to the hypothesis that decreases in vitamin D status in athletes may be related to the acute phase inflammatory response during exercise. In addition, the increased 24,25(OH)D₃ concentrations compared to what is observed in other species suggests metabolic variations in dogs that lead to enhanced disposal of vitamin D.     

Neutrophil Gelatinase‐Associated Lipocalin in Dogs With Sepsis Undergoing Emergency Laparotomy: A Prospective Case–Control Study

Background

Neutrophil gelatinase‐associated lipocalin (NGAL) is an early indicator of acute kidney injury (AKI) in dogs and its use has not been evaluated in dogs with sepsis.

Animals

Fifteen dogs with sepsis requiring laparotomy (study dogs) and 10 dogs undergoing surgery for intervertebral disc disease (control dogs).

Objective

To determine whether NGAL increases in dogs with sepsis undergoing emergency laparotomy and whether it is correlated with development of AKI and survival.

Methods

Longitudinal study conducted at a referral teaching hospital. Serum neutrophil gelatinase‐associated lipocalin (sNGAL), urinary NGAL normalized to urinary creatinine concentration (UNCR), and serum creatinine concentration were measured at 4 time points (admission, after anesthesia, and 24 and 48 hours postsurgery). Development of AKI (increase in serum creatinine concentration of 0.3 mg/dL) and in‐hospital mortality were recorded. Linear mixed‐model analysis was employed to assess differences between groups over time. Mann–Whitney U‐test was performed for comparison of continuous variables between groups and Chi square or Fisher''s exact tests were used to assess correlation between discrete data.

Results

Serum NGAL and UNCR were significantly higher in study dogs across all time points (P = .007 and P < .001, respectively) compared with controls. Urinary NGAL normalized to creatinine in the study group was not significantly different between survivors (n = 12) and nonsurvivors (n = 3). Dogs that received hydroxyethyl starch had significantly higher UNCR across all time points (P = .04) than those that did not.

Discussion—Conclusion

Serum neutrophil gelatinase‐associated lipocalin and UNCR are increased in dogs with sepsis requiring emergency laparotomy. Additional studies are needed to evaluate its role as a marker of AKI in this population.     

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long‐Term Follow‐Up Study

Background

Lagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long‐term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult‐onset epilepsies.

Hypothesis/Objectives

The objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood.

Animals

A total of 25 LR with a history of BFJE and 91 control dogs of the same breed.

Methods

Owners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dog''s activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case–control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy.

Results

Lagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P = .003; P = .021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood.

Conclusions and Clinical Importance

Although the long‐term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.