Copper-associated chronic hepatitis in Labrador Retrievers

This study summarizes the clinical and pathologic findings in 15 Labrador Retrievers with copper-associated chronic hepatitis (CACH). Our hypothesis was that this form of hepatitis is caused by a defect in hepatic copper metabolism, which most likely originates from a genetic defect. Affected Labradors consisted of 11 female and 4 male Labrador Retrievers. Eight family members of 2 of these patients were examined prospectively, as were 6 unrelated healthy Labrador Retrievers. All dogs were registered at the breed club. The average age at clinical presentation was 7 years (range, 2.5-10.5 years). All dogs were presented for anorexia, which was associated with vomiting in 8 patients. The diagnosis of CACH was based on histologic examination of liver biopsy specimens in all dogs, including semiquantitation of copper. A disproportionate increase in alanine aminotransferase (ALT) activity relative to alkaline phosphatase (ALP) activity, as well as the centrolobular localization of copper and the association of copper accumulation with hepatic lesions, suggested a primary copper storage disease rather than primary cholestatic liver disease causing copper accumulation. Mean hepatic copper concentration measured in related Labradors was 1,317 microg/g dry weight liver (range, 402-2,576 microg/g). Mean hepatic copper concentration of unrelated normal Labradors was 233 microg/g dry weight liver (range, 120-304 microg/g). Our findings support the hypothesis that a hereditary form of hepatitis occurs in Labrador retrievers and is caused by a defect in hepatic copper metabolism.     

Dietary Management of Labrador Retrievers with Subclinical Hepatic Copper Accumulation

Background

Genetic and environmental factors, including dietary copper intake, contribute to the pathogenesis of copper‐associated hepatitis in Labrador retrievers. Clinical disease is preceded by a subclinical phase in which copper accumulates in the liver.

Objective

To investigate the effect of a low‐copper, high‐zinc diet on hepatic copper concentration in Labrador retrievers with increased hepatic copper concentrations.

Animals

Twenty‐eight clinically healthy, client‐owned Labrador retrievers with a mean hepatic copper concentration of 919 ± 477 mg/kg dry weight liver (dwl) that were related to dogs previously diagnosed with clinical copper‐associated hepatitis.

Methods

Clinical trial in which dogs were fed a diet containing 1.3 ± 0.3 mg copper/Mcal and 64.3 ± 5.9 mg zinc/Mcal. Hepatic copper concentrations were determined in liver biopsy samples approximately every 6 months. Logistic regression was performed to investigate effects of sex, age, initial hepatic copper concentration and pedigree on the ability to normalize hepatic copper concentrations.

Results

In responders (15/28 dogs), hepatic copper concentrations decreased from a mean of 710 ± 216 mg/kg dwl copper to 343 ± 70 mg/kg dwl hepatic copper after a median of 7.1 months (range, 5.5–21.4 months). Dogs from a severely affected pedigree were at increased risk for inability to have their hepatic copper concentrations normalized with dietary treatment.

Conclusions and Clinical Importance

Feeding a low‐copper, high‐zinc diet resulted in a decrease in hepatic copper concentrations in a subset of clinically normal Labrador retrievers with previous hepatic copper accumulation. A positive response to diet may be influenced by genetic background. Determination of clinical benefit requires further study.     

Relationship among Plasma Amino Acids, C-Reactive Protein, Illness Severity, and Outcome in Critically Ill Dogs

Background: Alterations in circulating amino acids have been documented in animal models and in critically ill people but have not been evaluated in dogs with spontaneously occurring disease.
Hypothesis/Objectives: To compare amino acid concentrations in critically ill dogs and healthy controls and to investigate potential relationships among amino acids, markers of inflammation, illness severity, and clinical outcome.
Animals: Forty-eight critically ill dogs and 24 healthy control dogs.
Methods: Plasma was analyzed for amino acids and C-reactive protein (CRP) was measured in serum. The Fischer ratio (the molar ratio of branched chain amino acids [BCAA] to aromatic amino acids [AAA]) and survival prediction index (SPI2) were calculated.
Results: Median CRP concentrations were significantly higher in the critically ill dogs compared with controls ( P < .001). Critically ill dogs had significantly lower concentrations of alanine ( P = .001), arginine ( P < .001), citrulline ( P < .001), glycine ( P < .001), methionine ( P < .001), proline ( P < .001), and serine ( P = .001) but significantly higher concentrations of lysine ( P = .02) and phenylalanine ( P < .001; Table 1 ). This pattern resulted in a significantly lower Fischer ratio ( P = .001) in the critically ill group. Median SPI2 score was significantly higher in dogs that survived ( P = .03). Concentrations of arginine ( P = .02), isoleucine ( P = .01), leucine ( P = .04), serine ( P = .04), valine ( P = .04), total BCAA ( P = .03), and the Fischer ratio ( P = .03) were significantly higher in survivors compared with nonsurvivors.  

  Table 1.   Comparison between critically ill and healthy control dogs and among different subgroups of diseases within the critically ill group.     

4.

Comparison of cerebral cranium volumes between cavalier King Charles spaniels with Chiari-like malformation, small breed dogs and Labradors     

H. R. Cross    R. Cappello    C. Rusbridge 《The Journal of small animal practice》2009,50(8):399-405

O bjectives : To ascertain whether cavalier King Charles spaniels (CKCSs) have a proportionately smaller caudal fossa compared with other small dogs and with Labradors. To evaluate if cerebellar herniation in CKCS correlates with caudal fossa volume.
M ethods : In this retrospective study, three-dimensional images were created from magnetic resonance imaging brain series of 117 dogs (split into three groups: CKCS, Labradors and small breeds) from which the volumes of the fossae and brain parenchyma were calculated. These volumes were transformed into percentages of total cranial cavity and parenchyma volumes, respectively. The percentages were statistically compared among the groups. The percentage of herniated cerebellum in the CKCS was compared using linear regression with the caudal fossa and parenchyma percentages.
R esults : Cavalier King Charles spaniels had a proportionately smaller caudal fossa compared with Labradors (P=0·002) but not to small breeds (P=0·103). Their caudal fossa parenchyma was proportionately the same volume as Labradors (P=0·976) but greater than small breeds (P=0·005). No relationship was found for the per cent of cerebellum herniated.
C linical S ignificance : The results support mesoderm insufficiency or craniosynostosis as the pathogenesis of Chiari-like malformation (CM) in CKCS. It presents evidence for overcrowding of the caudal fossa due to a mismatch of brain parenchyma and fossa volumes as to why CKCS and not other small dogs are affected.     

5.

Antioxidant Status and Biomarkers of Oxidative Stress in Dogs with Lymphoma     

J.L. Winter  L.G. Barber  L. Freeman  P.C. Griessmayr  P.E. Milbury  J.B. Blumberg 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(2):311-316

Background: Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly diagnosed lymphoma before treatment and once in remission, with comparison with healthy controls.
Hypothesis: Dogs with lymphoma have increased oxidant and reduced antioxidant concentrations compared with healthy controls, and that these abnormalities normalize once remission is achieved.
Animals: Seventeen dogs with lymphoma and 10 healthy controls.
Methods: Prospective, observational study. Measures of oxidative stress [malondialdehyde and total isoprostanes (isoP)] and antioxidants [α-tocopherol, γ-tocopherol, oxygen radical absorbance capacity (ORAC), and glutathione peroxidase (GSHPx)] were assessed in dogs with newly diagnosed lymphoma before treatment compared with healthy control dogs. The same parameters were measured in the dogs with lymphoma on week 7 of the chemotherapy protocol when all dogs were in remission.
Results: At baseline, dogs with lymphoma had significantly lower α-tocopherol ( P <.001) and γ-tocopherol ( P = .003) but higher GSHPx ( P = .05), ORAC ( P = .001), and isoP ( P < .001) compared with healthy controls. In the dogs with lymphoma, α-tocopherol concentrations were higher ( P = .005) and ascorbic acid were lower ( P = .04) after treatment.
Conclusions and Clinical Importance: Results suggest that dogs with lymphoma have alterations in oxidant and antioxidant concentrations and that the status of some of these biomarkers normalize after remission. Further studies are warranted to determine whether antioxidant interventions to correct these are beneficial in the treatment of canine lymphoma.     

6.

Nutritional management of inherited copper-associated hepatitis in the Labrador retriever     

Hille Fieten  Vincent C. Biourge  Adrian L. Watson  Peter A.J. Leegwater  Ted S.G.A.M. van den Ingh  Jan Rothuizen 《Veterinary journal (London, England : 1997)》2014,199(3):429-433

Canine hereditary copper-associated hepatitis is characterized by gradual hepatic copper accumulation eventually leading to liver cirrhosis. Therapy is aimed at creating a negative copper balance with metal chelators, of which d-penicillamine is the most commonly used. d-penicillamine often causes gastro-intestinal side effects and life-long continuous therapy may lead to a deficiency of copper and zinc. The aim of the current study was to investigate the effect of a low-copper, high-zinc diet as an alternative to continuous d-penicillamine treatment for the long-term management of canine copper-associated hepatitis.Sixteen affected Labrador retrievers were followed for a median time period of 19.1 months (range, 5.9–39 months) after being effectively treated with d-penicillamine. The dogs were maintained on a diet containing 1.3 ± 0.3 mg copper/1000 kcal and 64.3 ± 5.9 mg zinc/1000 kcal. Liver biopsies were taken every 6 months for histological evaluation and copper determination. Plasma alanine aminotransferase (ALT) and alkaline phosphatase, as well as serum albumin were determined.Dietary treatment alone was sufficient to maintain hepatic copper concentration below 800 mg/kg dry weight liver in 12 dogs during the study period. Four dogs needed re-treatment with d-penicillamine. ALT activity and albumin concentration were not associated with hepatic copper concentration, but showed a significant association with the stage and grade of hepatitis respectively. In conclusion, a low-copper, high-zinc diet can be a valuable alternative to continuous d-penicillamine administration for long-term management of dogs with copper-associated hepatitis. The copper re-accumulation rate of an individual dog should be considered in the design of a long-term management protocol and in determining re-biopsy intervals.     

7.

Anthropometric measurements of the scapula, humerus, radius and ulna in Labrador dogs with and without elbow dysplasia     

Davidson PT  Bullock-Saxton J  Lisle A 《Australian veterinary journal》2008,86(11):425-428

Objective To determine if anthropometric measurements of the Labrador scapula, humerus, ulna and radius, or their ratios, are related to the presence of elbow dysplasia (ED). Methods Digital calliper measurements of the lengths of the left scapula, humerus, radius and ulna, and their ratios, were analysed by gender in 103 volunteer Labradors (41 dogs, 62 bitches) against the ED radiological scores derived by the International Elbow Working Group (IEWG). The IEWG score is an umbrella score used to classify for ED and includes fragmented coronoid process, osteochondritis dessicans, incongruity and ununited anconeal process, the last of which occurs rarely in Labradors. Results Of the 103 Labradors studied, 31 were diagnosed radiographically with ED (20 bitches (32%), 11 (27%) dogs). Scapula length was significantly shorter for bitches with ED (P = 0.02), but not for dogs with ED. However, dogs showed a trend for a difference in the ulna:radius ratio (P = 0.06), which bitches did not. Although a greater percentage of bitches than dogs had ED in this study, the difference was not statistically significant. Conclusions Labrador bitches diagnosed with ED have a shorter scapula, which is a new finding associated with this condition. The difference in presentation associated with gender is unexpected and further research is recommended.     

8.

Chronic hepatitis in Labrador Retrievers: clinical presentation and prognostic factors     

Shih JL  Keating JH  Freeman LM  Webster CR 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2007,21(1):33-39

BACKGROUND: An increased incidence of chronic hepatitis has been reported in Labrador Retrievers. HYPOTHESIS: A breed associated hepatopathy occurs in Labrador Retrievers. ANIMALS: Twenty-four client-owned Labrador Retrievers. METHODS: Medical records of dogs with histopathologic confirmation of chronic hepatitis were retrospectively reviewed. A clinical score based on clinical signs and the results of biochemical tests was generated for each dog. Hepatic biopsy specimens were scored for disease activity, fibrosis, and copper accumulation. RESULTS: The median age was 9.3 years (range, 3.9-14.0 years). Clinical signs included inappetence, vomiting, lethargy, and weight loss. All dogs had increases in serum activity of one or more hepatobiliary enzyme. Hyperbilirubinemia and hypoalbuminemia were present in 45% and 21% of dogs, respectively. The median clinical score was 2.9, with a range of 0-8. The median histopathology activity and the fibrosis scores were 3.5 (range, 1-6) and 3.0 (range, 0-4), respectively. Rhodanine-positive copper staining was present in 15 of 17 biopsy specimens, with a median score of 2.0 (range, 0-3). Median survival was 374 days (range, 1-2645 days). A prolonged prothrombin time (P = .013) and thrombocytopenia (P = .041) were associated with survival < 2 months. The presence of anorexia (P = .049), hypoglobulinemia (P = .045), or prolonged partial thromboplastin time (P = .033) were associated with shorter overall survival times. The clinical score correlated with survival time (P = .030) and histopathologic staging (P = .049). CONCLUSIONS AND CLINICAL IMPORTANCE: A progressive hepatopathy in Labrador Retrievers in this study was marked by chronic inflammation, fibrosis, and copper accumulation. A clinical scoring system that correlates with survival time may be useful as a noninvasive method to predict prognosis.     

9.

Use of zinc acetate to treat copper toxicosis in dogs.     

G J Brewer  R D Dick  W Schall  V Yuzbasiyan-Gurkan  T P Mullaney  C Pace  J Lindgren  M Thomas  G Padgett 《Journal of the American Veterinary Medical Association》1992,201(4):564-568

Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs.     

10.

Elevated canine pancreatic lipase immunoreactivity concentration in dogs with inflammatory bowel disease is associated with a negative outcome   总被引：1，自引：0，他引：1  

A. Kathrani    J. M. Steiner  J. Suchodolski  J. Eastwood    H. Syme    O. A. Garden  †  K. Allenspach 《The Journal of small animal practice》2009,50(3):126-132

O bjectives : To investigate whether elevated canine pancreatic lipase immunoreactivity (CPLI) concentrations in dogs with inflammatory bowel disease (IBD) is associated with a worse clinical outcome.
M ethods : Serum CPLI assays were performed on serum stored from cases diagnosed with IBD. Thirty-two dogs with CPLI results within the reference range were designated as the control group and 15 dogs had CPLI above the reference range. Clinical signs, age, serum lipase and amylase activities, serum albumin and cobalamin concentrations, abdominal ultrasound examination, histopathology on small intestinal biopsies, management of IBD and outcome were compared between the two groups.
R esults : No significant differences were found in clinical activity score (P=0·54), number of antibiotic-responsive disease cases (P=0·480), number of steroid-responsive disease cases (P=0·491), serum amylase activity (P=0·058), serum cobalamin concentration (P=0·61), serum albumin concentration (P=0·052), abdominal ultrasound score (P=0·23) and histopathology scores for IBD (P=0·74) between the two groups. Dogs with increased CPLI concentration were significantly older and had a higher serum lipase activity than dogs with a CPLI concentration within the normal reference range (P=0·001, P=0·001, respectively). Moreover, dogs with increased CPLI concentration responded poorly to steroid treatment (P=0·01) and were significantly more likely to be euthanased at follow-up (P=0·02).
C linical S ignificance : CPLI should be measured in cases of canine IBD as elevated CPLI was associated with a worse outcome.     

11.

Status Epilepticus and Epileptic Seizures in Dogs     

R. Zimmermann  V.-I. Hülsmeyer  C. Sauter-Louis  A. Fischer 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(5):970-976

Background: A special form of epileptic seizures (ES) is the life-threatening condition of status epilepticus (SE), which requires immediate and specific treatment based on a correct diagnosis of the underlying disease condition.
Hypothesis/Objectives: The objectives of this retrospective study were to determine prevalence of ES and SE in dogs presenting at a veterinary teaching hospital, to identify the etiology and relative risk (RR) for SE in general and at the onset of seizures. Furthermore the outcome for dogs suffering from SE was to be evaluated.
Animals: Three hundred and ninety-four dogs that were admitted to a veterinary teaching hospital (January 1, 2002 to March 31, 2008) with ES.
Methods: All medical records of dogs with ES were identified by screening the clinical documentation system and evaluated for inclusion in this retrospective study.
Results: Dogs with reactive seizures caused by poisoning had a significantly higher risk of developing SE ( P < .001; RR = 2.74), particularly as 1st manifestation of a seizure disorder ( P = .001; RR = 1.97). After SE, dogs with symptomatic epilepsy had a significantly lower probability of survival than dogs with idiopathic epilepsy ( P < .001) and reactive ESs ( P = .005).
Conclusion and Clinical Importance: In dogs showing SE as the 1st manifestation of a seizure disorder, intoxication should always be considered and appropriate investigations undertaken. Dogs with SE owing to toxicosis have more favorable outcomes than dogs with symptomatic epilepsy ( P < .001).     

12.

The efficacy of chlorhexidine gluconate in canine skin preparation – practice survey and clinical trials     

L. K. M. Evans    T. G. Knowles    G. Werrett    P. E. Holt 《The Journal of small animal practice》2009,50(9):458-465

O bjectives : To determine the use in practice and efficacy of different concentrations of chlorhexidine gluconate for canine pre-operative skin preparation.
M ethods : Questionnaires were used to establish which antiseptics and techniques were used for patients undergoing elective neutering. In a clinical study, five different concentrations of chlorhexidine gluconate – 0 per cent (tap water, as a control) 1, 2, 3 and 4 per cent – were tested on 50 dogs undergoing elective ovariohysterectomies and orchidectomies.
R esults : A variety of preparation practices occurred but only 21 per cent of the veterinary nurses surveyed were aware of the concentration and contact time they used whilst preparing animals. The clinical study revealed there was a significant difference (P<0·001) between the different concentrations used. All concentrations of chlorhexidine were significantly more effective than the control tap water. There was a tendency towards increasing efficacy as concentration increased from 1 to 4 per cent but this was not statistically significant.
C linical S ignificance : The lack of significant differences in efficacy between the different concentrations of chlorhexidine gluconate means that current practices may be adequate, although if the chlorhexidine gluconate concentrations and contact times used are unknown, they may be lower than those tested here and, possibly, ineffective, especially if contact times are short.     

13.

Concentrations of acute-phase proteins in dogs with steroid responsive meningitis-arteritis     

Bathen-Noethen A  Carlson R  Menzel D  Mischke R  Tipold A 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2008,22(5):1149-1156

Background: Measurement of concentrations of acute-phase proteins (APPs) is used as an aid in the diagnosis of a variety of diseases in animals.
Objective: To determine the concentration of APPs in dogs with steroid responsive meningitis-arteritis (SRMA) and other neurologic diseases.
Animals: One hundred and thirty-three dogs with neurologic diseases, 6 dogs with sepsis, and 8 healthy dogs were included in the study. Thirty-six dogs had SRMA (31 of which had monitoring), 14 dogs had other meningoencephalitides (ME), 32 had disk disease (IVDD/DLSS), 26 had tumors affecting the central nervous system (TCNS), and 25 had idiopathic epilepsy (IE).
Methods: Prospective, observational study: C-reactive protein (CRP), α₂-macroglobulin (AMG), and albumin concentrations were determined in the serum or plasma. CRP was also measured in the cerebrospinal fluid.
Results: Serum CRP was significantly higher in dogs with SRMA (     = 142 μg/mL ± 75) and sepsis (     = 114 μg/mL ± 67) in comparison with dogs with other neurologic diseases (     = 2.3–21 μg/mL; P < .001). There was no significant difference detected in AMG between groups. Serum albumin concentration was significantly lower ( P < .01) in dogs with SRMA (     = 3.2 g/dL ± 0.41) than in other groups (     = 3.6–3.9 g/dL). Serum CRP concentration of SRMA dogs correlated with alkaline phosphatase levels ( r = 0.515, P = .003).
Conclusions and Clinical Importance: CRP concentrations in serum are useful in diagnosis of dogs with SRMA. Serum CRP could be used as a monitoring parameter in treatment management of these dogs.     

14.

Hepatic Volume Measurements in Dogs with Extrahepatic Congenital Portosystemic Shunts before and after Surgical Attenuation     

A. Kummeling  D.J.E. Vrakking  J. Rothuizen  K.M. Gerritsen  F.J. van Sluijs 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2010,24(1):114-119

Background: In dogs with congenital portosystemic shunts (CPSS), the ability of the hypoplastic liver to grow is considered important for recovery after surgical shunt attenuation.
Objectives: This study investigated hepatic growth after extrahepatic shunt attenuation in dogs using magnetic resonance imaging (MRI) and computed tomography (CT).
Animals: Ten client-owned dogs with single extrahepatic CPSS.
Methods: Abdominal MRI, CT, or both were performed before and 8 days, 1, and 2 months after shunt attenuation. Liver volumes were calculated from the areas of the MRI or CT images.
Results: Before surgery, median liver volume was 18.2 cm³/kg body weight. Liver volume increased significantly after surgery. Growth was highest between days 0 and 8 and decreased afterward. Median liver volume was 28.8 cm³/kg at 2 months after attenuation. No significant differences in growth were found between dogs with complete or partial shunt closure or between dogs with complete or incomplete metabolic recovery. Volumes measured from consecutively performed MRI and CT images correlated well ( r = 0.980), but volumes from MRI images were significantly larger than volumes from CT images (6.8%; P = .008).
Conclusion and Clinical Importance: After shunt attenuation, rapid normalization of liver size was observed. Hepatic growth was not decreased in dogs after partial closure of CPSS or in dogs with subclinical, persistent shunting 2 months after surgery. CT is the preferred imaging method for volumetric estimation because of speed.     

15.

Calcium Reuptake Related Genes as a Cardiac Biomarker in Dogs with Chronic Mitral Valvular Insufficiency     

J.-S. Lee  S.-I. Pak  C. Hyun 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(4):832-839

     

16.

Radiographic measurement of the proximal and distal mechanical joint angles in the canine tibia     

Dismukes DI  Tomlinson JL  Fox DB  Cook JL  Song KJ 《Veterinary surgery : VS》2007,36(7):699-704

Objective— To describe a method for radiographic measurement of proximal and distal mechanical joint angles of the canine tibia. Normal ranges were established for a population of dogs, and specifically, Labrador retrievers, with cranial cruciate ligament rupture.
Study Design— Retrospective study.
Sample Population— Tibiae (n=105) of dogs evaluated for cranial cruciate ligament rupture; 70 tibiae were from Labrador retrievers, 35 tibiae were from other breeds.
Methods— Anatomic landmarks were established and craniocaudal radiographs were used to measure the mechanical medial proximal (mMPTA) and distal (mMDTA) tibial angles in the frontal plane.
Results— Means (±SD) for all tibiae were mMPTA, 93.30±1.78°, and mMDTA, 95.99±2.70°. For Labrador retrievers, means were mMPTA, 93.38±1.81°, and mMDTA 96.34±2.51°. No significant differences were detected between Labrador Retrievers and non-Labrador retrievers with respect to mMPTA (power=0.5) or mMDTA (power=0.342). Labrador Retrievers were significantly younger than non-Labradors ( P =.003).
Conclusion— A method for measurement of the mechanical joint angles of the canine tibia in the frontal plane was established and reference ranges for a population of dogs and Labrador Retrievers with cranial cruciate ligament rupture are reported.
Clinical Relevance— The established method of measurement and references ranges can be used to aid in diagnosis, determining indications, and surgical planning for angular limb deformities of the tibia, especially when affected bilaterally. The methodology and reference values may also be used for postoperative critique.     

17.

Effect of Experimental Hypothyroidism on Glomerular Filtration Rate and Plasma Creatinine Concentration in Dogs     

D.L. Panciera  H.P. Lefebvre 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(5):1045-1050

Background: Hypothyroidism affects renal function in a manner opposite the effects of hyperthyroidism.
Objective: To evaluate the effects of experimentally induced hypothyroidism on glomerular filtration rate (GFR) and basal plasma creatinine concentration in dogs.
Animals: Sixteen anestrous, female dogs.
Methods: Hypothyroidism was induced by administration of ¹³¹I in 8 dogs, and 8 healthy euthyroid dogs acted as controls. Exogenous plasma creatinine clearance (an estimate of GFR) was measured in all dogs before (control period) and 43–50 weeks after induction of hypothyroidism (posttreatment period). Other pharmacokinetic parameters of creatinine were also determined.
Results: No significant difference was observed for basal plasma creatinine concentration and creatinine clearance between control and hypothyroid dogs in the control period. In the posttreatment period, mean ± SD creatinine clearance in the hypothyroid group (2.13 ± 0.48 mL/min/kg) was lower ( P < .001) than that of the control group (3.20 ± 0.42 mL/kg/min). Nevertheless, basal plasma creatinine concentrations were not significantly different between the hypothyroid and control groups (0.74 ± 0.18 versus 0.70 ± 0.08 mg/dL, respectively) because endogenous production of creatinine was decreased in hypothyroid dogs (22 ± 3 versus 32 ± 5 mg/kg/d, P =.001).
Conclusion and Clinical Importance: Hypothyroidism causes a substantial decrease in GFR without altering plasma creatinine concentrations, indicating that GFR evaluation is needed to identify renal dysfunction in such patients.     

18.

Evaluation of a commercially available molybdate formulation and zinc oxide boluses in preventing hepatic copper accumulation and thus enzootic icterus in sheep     

Botha CJ  Shakespeare AS  Gehring R  van der Merwe D 《Journal of the South African Veterinary Association》2001,72(4):183-188

The efficacy of a molybdate formulation and a zinc oxide bolus as prophylactic agents for enzootic icterus was evaluated in sheep. Before copper loading, liver biopsies were performed on 12 male, 6-month-old, Mutton Merino sheep to determine hepatic copper (Cu) and zinc (Zn) concentrations. The animals were restrictively randomised according to liver copper concentrations to 3 treatment groups (n = 4) to achieve similar mean liver copper concentrations per group. All sheep received 4 ml/kg of a 0.5 % aqueous solution of CuSO4 5H2O intraruminally 7 days per week for 10 weeks. On Day 0 the sheep in the Mo-group were injected subcutaneously with 42 mg molybdenum (Mo) contained in a commercial molybdate formulation. The animals in the Zn-group each received a zinc oxide bolus, containing 43 g zinc oxide, via a rumen cannula. Treatment was repeated on Day 42. Four animals served as untreated controls. Urinary copper excretion, plasma copper concentration, haematocrit and glutamate dehydrogenase (GLDH) activity were determined throughout the trial. The animals were sacrificed after 10 weeks and liver samples were submitted for histopathological examination. Liver and kidney copper and zinc concentrations were determined. Neither the molybdate treatment nor the zinc oxide boluses prevented hepatic copper accumulation. The urinary copper excretion, plasma copper concentration, haematocrit and GLDH activity were not significantly different (P > 0.05) from the controls.     

19.

The influence of a novel organ perfusion solution on early graft function in canine renal autotransplantation     

Polyak MM  Grosche A  Towl S  Morton AJ 《Veterinary surgery : VS》2008,37(4):383-389

Objective— To evaluate the influence of a kidney perfusion solution on early graft function in dogs.
Study Design— Experimental, randomized study.
Animals— Intact adult male mongrel dogs (n=12).
Methods— Dogs had renal autograft transplantation without ureteroneocystotomy with contralateral nephrectomy. Kidney graft flushing with a novel organ perfusion solution was compared with flushing with saline (0.9% NaCl) solution. Serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured daily posttransplant for 7 days. Ultrasound-guided renal biopsy was performed on postoperative day 1 for electron microscopic evaluation. Dogs were euthanatized on day 7.
Results— All dogs completed the study. Cr and BUN concentrations of the saline group were significantly greater than the organ perfusion solution group on each postoperative day ( P =.01 for S Cr; P =.001 for BUN). Electron micrographs of nuclei and mitochondria from convoluted proximal tubule cells indicated profound ultrastructural disruptions in the saline group and mild ultrastructural disruptions in the organ perfusion solution group.
Conclusion— Flushing solution composition can influence early graft function in live donor kidney transplantation.
Clinical Relevance— Use of a specialized flushing solution can improve early graft function in canine kidney transplantation, independent of antigen-mediated events.     

20.

Serum cardiac troponin I concentration in dogs with ehrlichiosis     

Diniz PP  de Morais HS  Breitschwerdt EB  Schwartz DS 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2008,22(5):1136-1143

Background: Ehrlichiosis is a multisystemic disease with the potential to cause cardiomyocyte injury in naturally infected dogs.
Hypothesis: Myocardial injury occurs in dogs infected with Ehrlichia canis .
Animals: One-hundred and ninety-four dogs from Brazil with clinical and laboratory abnormalities indicative of ehrlichiosis. Sixteen healthy dogs served as controls.
Methods: Electrocardiogram, echocardiogram, noninvasive blood pressure measurement, and serum cardiac troponin I (cTnI) concentrations were evaluated. Serologic assays and PCR determined the exposure and infection status for E. canis, Anaplasma spp., Babesia canis vogeli, Bartonella spp., Borrelia burgdorferi, Dirofilaria immitis, Ehrlichia chaffeensis, Ehrlichia ewingii, Leishmania chagasi , and spotted-fever group Rickettsia . Dogs were assigned to groups according to PCR status: E. canis infected, infected with other vector-borne organisms, sick dogs lacking PCR evidence for infection, and healthy controls.
Results: E. canis -infected dogs had higher serum cTnI concentrations than controls (median: 0.04 ng/dL; range 0.04–9.12 ng/dL; control median: 0.04 ng/dL; range: 0.04–0.10 ng/dL; P = .012), and acute E. canis infection was associated with myocardial injury (odds ratio [OR]: 2.67, confidence interval [CI] 95%: 1.12–6.40, P = .027). Severity of anemia was correlated with increased risk of cardiomyocyte damage ( r = 0.84, P < .001). Dogs with clinical signs of systemic inflammatory response syndrome (SIRS) were at higher risk for myocardial injury than were other sick dogs (OR: 2.55, CI 95%: 1.31–4.95, P = .005).
Conclusions and Clinical Importance: Acute infection with E. canis is a risk factor for myocardial injury in naturally infected Brazilian dogs. Severity of anemia and SIRS might contribute to the pathophysiology of myocardial damage.     

Comparison of cerebral cranium volumes between cavalier King Charles spaniels with Chiari-like malformation, small breed dogs and Labradors

O bjectives : To ascertain whether cavalier King Charles spaniels (CKCSs) have a proportionately smaller caudal fossa compared with other small dogs and with Labradors. To evaluate if cerebellar herniation in CKCS correlates with caudal fossa volume.
M ethods : In this retrospective study, three-dimensional images were created from magnetic resonance imaging brain series of 117 dogs (split into three groups: CKCS, Labradors and small breeds) from which the volumes of the fossae and brain parenchyma were calculated. These volumes were transformed into percentages of total cranial cavity and parenchyma volumes, respectively. The percentages were statistically compared among the groups. The percentage of herniated cerebellum in the CKCS was compared using linear regression with the caudal fossa and parenchyma percentages.
R esults : Cavalier King Charles spaniels had a proportionately smaller caudal fossa compared with Labradors (P=0·002) but not to small breeds (P=0·103). Their caudal fossa parenchyma was proportionately the same volume as Labradors (P=0·976) but greater than small breeds (P=0·005). No relationship was found for the per cent of cerebellum herniated.
C linical S ignificance : The results support mesoderm insufficiency or craniosynostosis as the pathogenesis of Chiari-like malformation (CM) in CKCS. It presents evidence for overcrowding of the caudal fossa due to a mismatch of brain parenchyma and fossa volumes as to why CKCS and not other small dogs are affected.     

Antioxidant Status and Biomarkers of Oxidative Stress in Dogs with Lymphoma

Background: Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly diagnosed lymphoma before treatment and once in remission, with comparison with healthy controls.
Hypothesis: Dogs with lymphoma have increased oxidant and reduced antioxidant concentrations compared with healthy controls, and that these abnormalities normalize once remission is achieved.
Animals: Seventeen dogs with lymphoma and 10 healthy controls.
Methods: Prospective, observational study. Measures of oxidative stress [malondialdehyde and total isoprostanes (isoP)] and antioxidants [α-tocopherol, γ-tocopherol, oxygen radical absorbance capacity (ORAC), and glutathione peroxidase (GSHPx)] were assessed in dogs with newly diagnosed lymphoma before treatment compared with healthy control dogs. The same parameters were measured in the dogs with lymphoma on week 7 of the chemotherapy protocol when all dogs were in remission.
Results: At baseline, dogs with lymphoma had significantly lower α-tocopherol ( P <.001) and γ-tocopherol ( P = .003) but higher GSHPx ( P = .05), ORAC ( P = .001), and isoP ( P < .001) compared with healthy controls. In the dogs with lymphoma, α-tocopherol concentrations were higher ( P = .005) and ascorbic acid were lower ( P = .04) after treatment.
Conclusions and Clinical Importance: Results suggest that dogs with lymphoma have alterations in oxidant and antioxidant concentrations and that the status of some of these biomarkers normalize after remission. Further studies are warranted to determine whether antioxidant interventions to correct these are beneficial in the treatment of canine lymphoma.     

Nutritional management of inherited copper-associated hepatitis in the Labrador retriever

Canine hereditary copper-associated hepatitis is characterized by gradual hepatic copper accumulation eventually leading to liver cirrhosis. Therapy is aimed at creating a negative copper balance with metal chelators, of which d-penicillamine is the most commonly used. d-penicillamine often causes gastro-intestinal side effects and life-long continuous therapy may lead to a deficiency of copper and zinc. The aim of the current study was to investigate the effect of a low-copper, high-zinc diet as an alternative to continuous d-penicillamine treatment for the long-term management of canine copper-associated hepatitis.Sixteen affected Labrador retrievers were followed for a median time period of 19.1 months (range, 5.9–39 months) after being effectively treated with d-penicillamine. The dogs were maintained on a diet containing 1.3 ± 0.3 mg copper/1000 kcal and 64.3 ± 5.9 mg zinc/1000 kcal. Liver biopsies were taken every 6 months for histological evaluation and copper determination. Plasma alanine aminotransferase (ALT) and alkaline phosphatase, as well as serum albumin were determined.Dietary treatment alone was sufficient to maintain hepatic copper concentration below 800 mg/kg dry weight liver in 12 dogs during the study period. Four dogs needed re-treatment with d-penicillamine. ALT activity and albumin concentration were not associated with hepatic copper concentration, but showed a significant association with the stage and grade of hepatitis respectively. In conclusion, a low-copper, high-zinc diet can be a valuable alternative to continuous d-penicillamine administration for long-term management of dogs with copper-associated hepatitis. The copper re-accumulation rate of an individual dog should be considered in the design of a long-term management protocol and in determining re-biopsy intervals.     

Anthropometric measurements of the scapula, humerus, radius and ulna in Labrador dogs with and without elbow dysplasia

Objective To determine if anthropometric measurements of the Labrador scapula, humerus, ulna and radius, or their ratios, are related to the presence of elbow dysplasia (ED). Methods Digital calliper measurements of the lengths of the left scapula, humerus, radius and ulna, and their ratios, were analysed by gender in 103 volunteer Labradors (41 dogs, 62 bitches) against the ED radiological scores derived by the International Elbow Working Group (IEWG). The IEWG score is an umbrella score used to classify for ED and includes fragmented coronoid process, osteochondritis dessicans, incongruity and ununited anconeal process, the last of which occurs rarely in Labradors. Results Of the 103 Labradors studied, 31 were diagnosed radiographically with ED (20 bitches (32%), 11 (27%) dogs). Scapula length was significantly shorter for bitches with ED (P = 0.02), but not for dogs with ED. However, dogs showed a trend for a difference in the ulna:radius ratio (P = 0.06), which bitches did not. Although a greater percentage of bitches than dogs had ED in this study, the difference was not statistically significant. Conclusions Labrador bitches diagnosed with ED have a shorter scapula, which is a new finding associated with this condition. The difference in presentation associated with gender is unexpected and further research is recommended.     

Chronic hepatitis in Labrador Retrievers: clinical presentation and prognostic factors

BACKGROUND: An increased incidence of chronic hepatitis has been reported in Labrador Retrievers. HYPOTHESIS: A breed associated hepatopathy occurs in Labrador Retrievers. ANIMALS: Twenty-four client-owned Labrador Retrievers. METHODS: Medical records of dogs with histopathologic confirmation of chronic hepatitis were retrospectively reviewed. A clinical score based on clinical signs and the results of biochemical tests was generated for each dog. Hepatic biopsy specimens were scored for disease activity, fibrosis, and copper accumulation. RESULTS: The median age was 9.3 years (range, 3.9-14.0 years). Clinical signs included inappetence, vomiting, lethargy, and weight loss. All dogs had increases in serum activity of one or more hepatobiliary enzyme. Hyperbilirubinemia and hypoalbuminemia were present in 45% and 21% of dogs, respectively. The median clinical score was 2.9, with a range of 0-8. The median histopathology activity and the fibrosis scores were 3.5 (range, 1-6) and 3.0 (range, 0-4), respectively. Rhodanine-positive copper staining was present in 15 of 17 biopsy specimens, with a median score of 2.0 (range, 0-3). Median survival was 374 days (range, 1-2645 days). A prolonged prothrombin time (P = .013) and thrombocytopenia (P = .041) were associated with survival < 2 months. The presence of anorexia (P = .049), hypoglobulinemia (P = .045), or prolonged partial thromboplastin time (P = .033) were associated with shorter overall survival times. The clinical score correlated with survival time (P = .030) and histopathologic staging (P = .049). CONCLUSIONS AND CLINICAL IMPORTANCE: A progressive hepatopathy in Labrador Retrievers in this study was marked by chronic inflammation, fibrosis, and copper accumulation. A clinical scoring system that correlates with survival time may be useful as a noninvasive method to predict prognosis.     

Use of zinc acetate to treat copper toxicosis in dogs.

Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs.     

Elevated canine pancreatic lipase immunoreactivity concentration in dogs with inflammatory bowel disease is associated with a negative outcome

O bjectives : To investigate whether elevated canine pancreatic lipase immunoreactivity (CPLI) concentrations in dogs with inflammatory bowel disease (IBD) is associated with a worse clinical outcome.
M ethods : Serum CPLI assays were performed on serum stored from cases diagnosed with IBD. Thirty-two dogs with CPLI results within the reference range were designated as the control group and 15 dogs had CPLI above the reference range. Clinical signs, age, serum lipase and amylase activities, serum albumin and cobalamin concentrations, abdominal ultrasound examination, histopathology on small intestinal biopsies, management of IBD and outcome were compared between the two groups.
R esults : No significant differences were found in clinical activity score (P=0·54), number of antibiotic-responsive disease cases (P=0·480), number of steroid-responsive disease cases (P=0·491), serum amylase activity (P=0·058), serum cobalamin concentration (P=0·61), serum albumin concentration (P=0·052), abdominal ultrasound score (P=0·23) and histopathology scores for IBD (P=0·74) between the two groups. Dogs with increased CPLI concentration were significantly older and had a higher serum lipase activity than dogs with a CPLI concentration within the normal reference range (P=0·001, P=0·001, respectively). Moreover, dogs with increased CPLI concentration responded poorly to steroid treatment (P=0·01) and were significantly more likely to be euthanased at follow-up (P=0·02).
C linical S ignificance : CPLI should be measured in cases of canine IBD as elevated CPLI was associated with a worse outcome.     

Status Epilepticus and Epileptic Seizures in Dogs

Background: A special form of epileptic seizures (ES) is the life-threatening condition of status epilepticus (SE), which requires immediate and specific treatment based on a correct diagnosis of the underlying disease condition.
Hypothesis/Objectives: The objectives of this retrospective study were to determine prevalence of ES and SE in dogs presenting at a veterinary teaching hospital, to identify the etiology and relative risk (RR) for SE in general and at the onset of seizures. Furthermore the outcome for dogs suffering from SE was to be evaluated.
Animals: Three hundred and ninety-four dogs that were admitted to a veterinary teaching hospital (January 1, 2002 to March 31, 2008) with ES.
Methods: All medical records of dogs with ES were identified by screening the clinical documentation system and evaluated for inclusion in this retrospective study.
Results: Dogs with reactive seizures caused by poisoning had a significantly higher risk of developing SE ( P < .001; RR = 2.74), particularly as 1st manifestation of a seizure disorder ( P = .001; RR = 1.97). After SE, dogs with symptomatic epilepsy had a significantly lower probability of survival than dogs with idiopathic epilepsy ( P < .001) and reactive ESs ( P = .005).
Conclusion and Clinical Importance: In dogs showing SE as the 1st manifestation of a seizure disorder, intoxication should always be considered and appropriate investigations undertaken. Dogs with SE owing to toxicosis have more favorable outcomes than dogs with symptomatic epilepsy ( P < .001).     

The efficacy of chlorhexidine gluconate in canine skin preparation – practice survey and clinical trials

O bjectives : To determine the use in practice and efficacy of different concentrations of chlorhexidine gluconate for canine pre-operative skin preparation.
M ethods : Questionnaires were used to establish which antiseptics and techniques were used for patients undergoing elective neutering. In a clinical study, five different concentrations of chlorhexidine gluconate – 0 per cent (tap water, as a control) 1, 2, 3 and 4 per cent – were tested on 50 dogs undergoing elective ovariohysterectomies and orchidectomies.
R esults : A variety of preparation practices occurred but only 21 per cent of the veterinary nurses surveyed were aware of the concentration and contact time they used whilst preparing animals. The clinical study revealed there was a significant difference (P<0·001) between the different concentrations used. All concentrations of chlorhexidine were significantly more effective than the control tap water. There was a tendency towards increasing efficacy as concentration increased from 1 to 4 per cent but this was not statistically significant.
C linical S ignificance : The lack of significant differences in efficacy between the different concentrations of chlorhexidine gluconate means that current practices may be adequate, although if the chlorhexidine gluconate concentrations and contact times used are unknown, they may be lower than those tested here and, possibly, ineffective, especially if contact times are short.     

Concentrations of acute-phase proteins in dogs with steroid responsive meningitis-arteritis

Background: Measurement of concentrations of acute-phase proteins (APPs) is used as an aid in the diagnosis of a variety of diseases in animals.
Objective: To determine the concentration of APPs in dogs with steroid responsive meningitis-arteritis (SRMA) and other neurologic diseases.
Animals: One hundred and thirty-three dogs with neurologic diseases, 6 dogs with sepsis, and 8 healthy dogs were included in the study. Thirty-six dogs had SRMA (31 of which had monitoring), 14 dogs had other meningoencephalitides (ME), 32 had disk disease (IVDD/DLSS), 26 had tumors affecting the central nervous system (TCNS), and 25 had idiopathic epilepsy (IE).
Methods: Prospective, observational study: C-reactive protein (CRP), α₂-macroglobulin (AMG), and albumin concentrations were determined in the serum or plasma. CRP was also measured in the cerebrospinal fluid.
Results: Serum CRP was significantly higher in dogs with SRMA (     = 142 μg/mL ± 75) and sepsis (     = 114 μg/mL ± 67) in comparison with dogs with other neurologic diseases (     = 2.3–21 μg/mL; P < .001). There was no significant difference detected in AMG between groups. Serum albumin concentration was significantly lower ( P < .01) in dogs with SRMA (     = 3.2 g/dL ± 0.41) than in other groups (     = 3.6–3.9 g/dL). Serum CRP concentration of SRMA dogs correlated with alkaline phosphatase levels ( r = 0.515, P = .003).
Conclusions and Clinical Importance: CRP concentrations in serum are useful in diagnosis of dogs with SRMA. Serum CRP could be used as a monitoring parameter in treatment management of these dogs.     

Hepatic Volume Measurements in Dogs with Extrahepatic Congenital Portosystemic Shunts before and after Surgical Attenuation

Background: In dogs with congenital portosystemic shunts (CPSS), the ability of the hypoplastic liver to grow is considered important for recovery after surgical shunt attenuation.
Objectives: This study investigated hepatic growth after extrahepatic shunt attenuation in dogs using magnetic resonance imaging (MRI) and computed tomography (CT).
Animals: Ten client-owned dogs with single extrahepatic CPSS.
Methods: Abdominal MRI, CT, or both were performed before and 8 days, 1, and 2 months after shunt attenuation. Liver volumes were calculated from the areas of the MRI or CT images.
Results: Before surgery, median liver volume was 18.2 cm³/kg body weight. Liver volume increased significantly after surgery. Growth was highest between days 0 and 8 and decreased afterward. Median liver volume was 28.8 cm³/kg at 2 months after attenuation. No significant differences in growth were found between dogs with complete or partial shunt closure or between dogs with complete or incomplete metabolic recovery. Volumes measured from consecutively performed MRI and CT images correlated well ( r = 0.980), but volumes from MRI images were significantly larger than volumes from CT images (6.8%; P = .008).
Conclusion and Clinical Importance: After shunt attenuation, rapid normalization of liver size was observed. Hepatic growth was not decreased in dogs after partial closure of CPSS or in dogs with subclinical, persistent shunting 2 months after surgery. CT is the preferred imaging method for volumetric estimation because of speed.     

Radiographic measurement of the proximal and distal mechanical joint angles in the canine tibia

Objective— To describe a method for radiographic measurement of proximal and distal mechanical joint angles of the canine tibia. Normal ranges were established for a population of dogs, and specifically, Labrador retrievers, with cranial cruciate ligament rupture.
Study Design— Retrospective study.
Sample Population— Tibiae (n=105) of dogs evaluated for cranial cruciate ligament rupture; 70 tibiae were from Labrador retrievers, 35 tibiae were from other breeds.
Methods— Anatomic landmarks were established and craniocaudal radiographs were used to measure the mechanical medial proximal (mMPTA) and distal (mMDTA) tibial angles in the frontal plane.
Results— Means (±SD) for all tibiae were mMPTA, 93.30±1.78°, and mMDTA, 95.99±2.70°. For Labrador retrievers, means were mMPTA, 93.38±1.81°, and mMDTA 96.34±2.51°. No significant differences were detected between Labrador Retrievers and non-Labrador retrievers with respect to mMPTA (power=0.5) or mMDTA (power=0.342). Labrador Retrievers were significantly younger than non-Labradors ( P =.003).
Conclusion— A method for measurement of the mechanical joint angles of the canine tibia in the frontal plane was established and reference ranges for a population of dogs and Labrador Retrievers with cranial cruciate ligament rupture are reported.
Clinical Relevance— The established method of measurement and references ranges can be used to aid in diagnosis, determining indications, and surgical planning for angular limb deformities of the tibia, especially when affected bilaterally. The methodology and reference values may also be used for postoperative critique.     

Effect of Experimental Hypothyroidism on Glomerular Filtration Rate and Plasma Creatinine Concentration in Dogs

Background: Hypothyroidism affects renal function in a manner opposite the effects of hyperthyroidism.
Objective: To evaluate the effects of experimentally induced hypothyroidism on glomerular filtration rate (GFR) and basal plasma creatinine concentration in dogs.
Animals: Sixteen anestrous, female dogs.
Methods: Hypothyroidism was induced by administration of ¹³¹I in 8 dogs, and 8 healthy euthyroid dogs acted as controls. Exogenous plasma creatinine clearance (an estimate of GFR) was measured in all dogs before (control period) and 43–50 weeks after induction of hypothyroidism (posttreatment period). Other pharmacokinetic parameters of creatinine were also determined.
Results: No significant difference was observed for basal plasma creatinine concentration and creatinine clearance between control and hypothyroid dogs in the control period. In the posttreatment period, mean ± SD creatinine clearance in the hypothyroid group (2.13 ± 0.48 mL/min/kg) was lower ( P < .001) than that of the control group (3.20 ± 0.42 mL/kg/min). Nevertheless, basal plasma creatinine concentrations were not significantly different between the hypothyroid and control groups (0.74 ± 0.18 versus 0.70 ± 0.08 mg/dL, respectively) because endogenous production of creatinine was decreased in hypothyroid dogs (22 ± 3 versus 32 ± 5 mg/kg/d, P =.001).
Conclusion and Clinical Importance: Hypothyroidism causes a substantial decrease in GFR without altering plasma creatinine concentrations, indicating that GFR evaluation is needed to identify renal dysfunction in such patients.     

Evaluation of a commercially available molybdate formulation and zinc oxide boluses in preventing hepatic copper accumulation and thus enzootic icterus in sheep

The efficacy of a molybdate formulation and a zinc oxide bolus as prophylactic agents for enzootic icterus was evaluated in sheep. Before copper loading, liver biopsies were performed on 12 male, 6-month-old, Mutton Merino sheep to determine hepatic copper (Cu) and zinc (Zn) concentrations. The animals were restrictively randomised according to liver copper concentrations to 3 treatment groups (n = 4) to achieve similar mean liver copper concentrations per group. All sheep received 4 ml/kg of a 0.5 % aqueous solution of CuSO4 5H2O intraruminally 7 days per week for 10 weeks. On Day 0 the sheep in the Mo-group were injected subcutaneously with 42 mg molybdenum (Mo) contained in a commercial molybdate formulation. The animals in the Zn-group each received a zinc oxide bolus, containing 43 g zinc oxide, via a rumen cannula. Treatment was repeated on Day 42. Four animals served as untreated controls. Urinary copper excretion, plasma copper concentration, haematocrit and glutamate dehydrogenase (GLDH) activity were determined throughout the trial. The animals were sacrificed after 10 weeks and liver samples were submitted for histopathological examination. Liver and kidney copper and zinc concentrations were determined. Neither the molybdate treatment nor the zinc oxide boluses prevented hepatic copper accumulation. The urinary copper excretion, plasma copper concentration, haematocrit and GLDH activity were not significantly different (P > 0.05) from the controls.     

The influence of a novel organ perfusion solution on early graft function in canine renal autotransplantation

Objective— To evaluate the influence of a kidney perfusion solution on early graft function in dogs.
Study Design— Experimental, randomized study.
Animals— Intact adult male mongrel dogs (n=12).
Methods— Dogs had renal autograft transplantation without ureteroneocystotomy with contralateral nephrectomy. Kidney graft flushing with a novel organ perfusion solution was compared with flushing with saline (0.9% NaCl) solution. Serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured daily posttransplant for 7 days. Ultrasound-guided renal biopsy was performed on postoperative day 1 for electron microscopic evaluation. Dogs were euthanatized on day 7.
Results— All dogs completed the study. Cr and BUN concentrations of the saline group were significantly greater than the organ perfusion solution group on each postoperative day ( P =.01 for S Cr; P =.001 for BUN). Electron micrographs of nuclei and mitochondria from convoluted proximal tubule cells indicated profound ultrastructural disruptions in the saline group and mild ultrastructural disruptions in the organ perfusion solution group.
Conclusion— Flushing solution composition can influence early graft function in live donor kidney transplantation.
Clinical Relevance— Use of a specialized flushing solution can improve early graft function in canine kidney transplantation, independent of antigen-mediated events.     

Serum cardiac troponin I concentration in dogs with ehrlichiosis

Background: Ehrlichiosis is a multisystemic disease with the potential to cause cardiomyocyte injury in naturally infected dogs.
Hypothesis: Myocardial injury occurs in dogs infected with Ehrlichia canis .
Animals: One-hundred and ninety-four dogs from Brazil with clinical and laboratory abnormalities indicative of ehrlichiosis. Sixteen healthy dogs served as controls.
Methods: Electrocardiogram, echocardiogram, noninvasive blood pressure measurement, and serum cardiac troponin I (cTnI) concentrations were evaluated. Serologic assays and PCR determined the exposure and infection status for E. canis, Anaplasma spp., Babesia canis vogeli, Bartonella spp., Borrelia burgdorferi, Dirofilaria immitis, Ehrlichia chaffeensis, Ehrlichia ewingii, Leishmania chagasi , and spotted-fever group Rickettsia . Dogs were assigned to groups according to PCR status: E. canis infected, infected with other vector-borne organisms, sick dogs lacking PCR evidence for infection, and healthy controls.
Results: E. canis -infected dogs had higher serum cTnI concentrations than controls (median: 0.04 ng/dL; range 0.04–9.12 ng/dL; control median: 0.04 ng/dL; range: 0.04–0.10 ng/dL; P = .012), and acute E. canis infection was associated with myocardial injury (odds ratio [OR]: 2.67, confidence interval [CI] 95%: 1.12–6.40, P = .027). Severity of anemia was correlated with increased risk of cardiomyocyte damage ( r = 0.84, P < .001). Dogs with clinical signs of systemic inflammatory response syndrome (SIRS) were at higher risk for myocardial injury than were other sick dogs (OR: 2.55, CI 95%: 1.31–4.95, P = .005).
Conclusions and Clinical Importance: Acute infection with E. canis is a risk factor for myocardial injury in naturally infected Brazilian dogs. Severity of anemia and SIRS might contribute to the pathophysiology of myocardial damage.