Serum Acute Phase Protein Concentrations in Dogs with Autoimmune Hemolytic Anemia

Background: Serial monitoring of acute phase protein (APP) concentrations in canine autoimmune hemolytic anemia (AIHA) has not been reported.
Hypotheses: Acute canine AIHA is accompanied by an acute phase response (APR) characterized by increased C-reactive protein (CRP) and α1-acid glycoprotein (AAG) concentrations and decreased albumin concentrations.
Animals: Twenty-seven dogs with AIHA and 11 control dogs.
Methods: Prospective, cohort study. CRP, AAG, and albumin concentrations, white blood cell (WBC) count, and packed cell volume (PCV) were determined at admission (day 1), every 48 hours until death or discharge, and on days 30, 90, 180, and 365.
Results: Compared with controls, CRP and AAG concentrations were increased and albumin concentration was decreased in dogs with AIHA (days 1–7; P < .002) and normalized with disease stabilization (days 9–365; P > .05). APP concentrations on day 1 were not predictive of survival, duration of hospitalization, or number of blood transfusions ( P = .153–.940). PCV correlated with APP concentrations over time (CRP r =−.600, AAG r =−.665, albumin r = .533; P < .0001) as did WBC count (CRP r = .253, AAG r = .486, albumin r =−.246; P < .006). Day 1 CRP concentration was lower for dogs that received corticosteroids before referral (115.3 μg/mL) compared with dogs that did not (191.2 μg/mL; P = .02).
Conclusions: An APR occurs in canine AIHA. Initial APP concentrations are not predictive of acute survival, correlate with hematologic markers of remission, and normalize rapidly with disease stabilization.     

Glutathione, Cysteine, and Ascorbate Concentrations in Clinically Ill Dogs and Cats

Background: Oxidative stress plays a role in the pathogenesis of many systemic diseases. Hospitalized human patients are glutathione, cysteine, and ascorbate deficient, and antioxidant depletion has been correlated with poor clinical outcome. To date little is known about antioxidant concentrations in hospitalized veterinary patients. The purpose of this study was to determine whether ascorbate, cysteine, or glutathione depletion is present in ill dogs and cats compared with healthy controls.
Hypothesis: Clinically ill dogs and cats would be antioxidant depleted, and depletion would correlate with illness severity and clinical outcome.
Animals: Clinically ill client-owned dogs (n = 61) and cats (n = 37), healthy control dogs (n = 37) and cats (n = 33).
Methods: Prospective, observational, case control study. Erythrocyte reduced glutathione, plasma cysteine, and plasma ascorbate were quantified using high-performance liquid chromatography.
Results: Clinically ill dogs had significantly lower erythrocyte glutathione concentrations (1.22 mM, range 0.55–3.61) compared with controls (1.91 mM, range 0.87–3.51; P = .0004), and glutathione depletion correlated with both illness severity ( P = .038) and mortality ( P = .010). Cats had higher ascorbate concentrations when ill (10.65 μM, range 1.13–25.26) compared with controls (3.68 μM, range 0.36–13.57; P = .0009).
Conclusions and Clinical Importance: Clinically ill dogs had decreased erythrocyte glutathione concentrations, which could be a marker of illness severity and prognostic of a poor outcome. Clinically ill cats had an unexpectedly high plasma ascorbate, which could represent a unique species response to oxidative stress.     

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.

Efficacy of Combination Chemotherapy for Treatment of Gastrointestinal Lymphoma in Dogs     

K.M. Rassnick  A.S. Moore  K.E. Collister  N.C. Northrup  O. Kristal  J.D. Chretin  D.B. Bailey 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(2):317-322

Background: Chemotherapy for multicentric canine lymphoma has favorable results. The gastrointestinal (GI) tract is the most common extranodal site of canine lymphoma, but there have been no prospective studies to determine outcome when dogs with GI lymphoma are treated with chemotherapy.
Hypothesis: Treatment with a multiagent chemotherapy protocol is associated with a poor outcome in dogs with GI lymphoma.
Animals: Eighteen dogs with histologically confirmed GI lymphoma.
Methods: Prospective clinical trial in which dogs with GI lymphoma were treated with a 20-week combination chemotherapy protocol consisting of induction and consolidation phases.
Results: Thirteen dogs had primary GI lymphoma and 5 had multicentric lymphoma with GI involvement. The majority of the lymphomas (63%) were of T-cell origin. Overall remission rate was 56%; 9 dogs achieved a complete remission for a median of 86 days (range, 22–420 days) and 1 dog achieved a partial remission for 26 days. Overall median survival time was 77 days (range, 6–700 days). Dogs that failed to achieve a remission (10 versus 117 days; P = .002) or had diarrhea at initial presentation (70 versus 700 days; P < .001) had shorter survival times.
Conclusion and Clinical Importance: The response and survival of dogs with GI lymphoma treated with multiagent chemotherapy is poor but long-term survival is possible.     

5.

Serial determination of biomarkers of oxidative stress and antioxidant status in dogs with naturally occurring gastric dilatation-volvulus     

Thomas G. Walker  DVM  DACVECC    Daniel L. Chan  DVM  DACVECC  DACVN    Lisa M. Freeman  DVM  PhD  DACVN    Paul E. Milbury  PhD    Jeffrey B. Blumberg  PhD 《Journal of Veterinary Emergency and Critical Care》2007,17(3):250-256

Objective: To serially determine the biomarkers of oxidative stress and antioxidant status of dogs with gastric dilatation‐volvulus (GDV) over 48 hours. Design: Prospective study. Setting: Veterinary teaching hospital intensive care unit. Animals: Thirteen client‐owned dogs with GDV. Interventions: None. Measurement and main results: For all dogs, biomarkers of oxidative stress and antioxidant status were ascertained. Indicators of oxidative stress measured included F_2α‐isoprostanes (isoprostanes) and malondialdehyde (MDA). Vitamin C, vitamin E, glutathione peroxidase (GSHPx), and oxygen radical absorbance capacity (ORAC) were measured to assess antioxidant status. Oxidants and antioxidants were measured at the time of admission and at 24 and 48 hours post‐admission. There were significant decreases in vitamin E (P=0.002), vitamin C (P=0.001), ORAC (P=0.02), and MDA (P=0.001) during hospitalization. There was no significant change in GSHPx and isoprostane concentrations over time. Conclusion: Oxidative stress and antioxidant capacity in dogs with GDV change over time. Further studies measuring oxidative stress in more severely affected dogs and performing measurements earlier in the disease process may be beneficial in determining when oxidative stress is most severe during the course of GDV management.     

6.

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.     

7.

An hGM‐CSF DNA‐Cationic Lipid Complexed Autologous Tumor Cell Vaccine did not Improve Remission Duration in Dogs with Lymphoma     

M. M. Turek  D. H. Thamm  A. M. Mitzey  I. D. Kurzman  M. K. Huelsmeyer  R. R. Dubielzig  D. M.  Vail 《Veterinary and comparative oncology》2005,3(1):59-59

Introduction:  Lymphoma is one of the most common cancers in dogs and while clinical remission can be induced using chemotherapy, very few dogs are cured. Since cytokine‐adjuvanted autologous whole‐tumor‐cell vaccines (ATCV) can induce potent antitumor immune responses against otherwise non‐immunogenic cancers we initiated a study of such an approach in dogs with lymphoma.
Methods:  Following achievement of a complete remission using a 19‐week CHOP‐based chemotherapy protocol, 51 dogs with B‐cell lymphoma were randomized to receive 8 treatments (4 weekly, then 4 additional at q2wk intervals) of vaccine or lipid‐equivalent placebo. Dogs were followed monthly for assessment of remission duration and survival. Surrogate indices of immune response (delayed‐type hypersensitivity, interferon‐γ quantitative RT‐PCR, lymphocyte proliferation, and flow cytometry for lymphoma‐specific antibodies) were also investigated before and after vaccination.
Results:  No significant difference in median remission duration was observed between dogs receiving vaccine (277 days) or placebo (258 days); the Kaplan‐Meier curves were virtually super‐imposable. No significant differences in surrogate indices of immune response were noted pre‐ and post‐vaccination.
Conclusions:  In this context, an hGM‐CSF DNA‐cationic lipid complexed ATCV vaccine did not enhance remission duration in dogs with lymphoma, likely due to lack of vaccine‐induced tumor‐specific immunity.     

8.

Serum C-reactive protein concentration as an indicator of remission status in dogs with multicentric lymphoma     

Nielsen L  Toft N  Eckersall PD  Mellor DJ  Morris JS 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2007,21(6):1231-1236

BACKGROUND: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. OBJECTIVE: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. ANIMALS: Twenty-two dogs with untreated multicentric lymphoma. METHODS: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. RESULTS: Before therapy, a statistically significant majority of the dogs (P = .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P < .001). CRP concentrations of dogs in complete remission (median, 1.91; range, 0.2-103) were significantly different (P = .031) from those of dogs with partial remission (median, 2.48; range, 0-89), stable disease (median, 1.77; range, 1.03-42.65), or progressive disease (median, 8.7; range, 0-82.5). There was profound variation of CRP measurements within each dog. CONCLUSIONS: CRP is useful in determining complete remission status after treatment with cytotoxic drugs. However, the individual variation between dogs means CRP concentration is not sufficiently different in other remission states to permit its use in monitoring progression of the disease. Greater reliability in determining remission status might be achieved by combining CRP concentration with other serum markers.     

9.

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.     

10.

Alterations in Lipoprotein Profiles in Dogs With Lymphoma     

Gregory K. Ogilvie  Richard B. Ford  David M. Vail  Lisa M. Walters  M. D. Salman  C. Babineau  Martin J. Fettman 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》1994,8(1):62-66

After a 12-hour fast, blood samples were obtained from 31 dogs with previously untreated lymphoma. Blood samples were also collected from 16 of these dogs after up to 5 treatments with doxorubicin (30 mg/m² intravenously every 3 weeks). All 16 dogs underwent complete remission. Five dogs were re-evaluated after relapse and after overt signs of cancer cachexia had become clinically apparent. Samples were assayed for 8 quantitative parameters: total cholesterol (T-CH) and total triglyceride (T-TG) concentrations, and the concentration of cholesterol and triglyceride in each of the three major lipoprotein fractions, very-low-density lipoprotein (VLDL-CH and VLDL-TG), low-density lipoprotein (LDL-CH and LDL-TG), and high-density lipoprotein (HDL-CH and HDL-TG). The results were compared with those from 20 healthy control dogs of similar weight and age before and 3 weeks after being given one dose of doxorubicin (30 mg/m² intravenously). The administration of doxorubicin to control dogs resulted in a significant (P> .05) decrease in T-CH, LDL-CH, and HDL-CH, as well as a significant increase in VLOL-TG and HDL-TG. When compared with untreated controls, untreated dogs with lymphoma had significantly higher concentrations of VLDL-CH, T-TG, VLDL-TG, LDL-TG, and HDL-TG, and significantly lower concentrations of HDL-CH. HDL-TG and VLDL-TG concentrations from dogs with lymphoma were significantly increased above pretreatment values after relapse and development of overt signs of cancer cachexia. Dogs in remission that were evaluated after one dose of doxorubicin had significantly higher concentrations of T-CH, VLDL-CH, T-TG, and LDL-TG when compared with controls that were evaluated after an identical dose of doxorubicin. HDL-TG increased significantly over pretreatment values in dogs with lymphoma after doxorubicin therapy. These results suggest that dogs with lymphoma have significant alterations in lipid profiles, and with the possible exception of HDL-CH, these abnormalities do not normalize when clinical remission is obtained.     

11.

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

     

12.

Effects of dietary modification in dogs with early chronic valvular disease     

Freeman LM  Rush JE  Markwell PJ 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2006,20(5):1116-1126

Background:The potential benefits of nutritional modification in early canine cardiac disease are not known.
Hypothesis:We hypothesized that echocardiographic, neuroendocrine, and nutritional variables will differ between dogs with asymptomatic chronic valvular disease (CVD) and healthy controls, and that a moderately reduced sodium diet enriched with antioxidants, n-3 fatty acids, taurine, carnitine, and arginine will alter these variables in dogs with CVD.
Methods: Echocardiography was performed and blood was collected. After baseline comparison with healthy controls, all dogs with CVD were fed a low-sodium run-in diet for 4 weeks, reevaluated, and then randomized to receive either the cardiac diet or a placebo diet for 4 weeks.
Results: At baseline, dogs with CVD (n = 29) had significantly lower circulating sodium, chloride, arginine, and methionine concentrations and higher plasma concentrations of atrial natriuretic peptide compared to healthy controls. In dogs with CVD, plasma aldosterone concentration and heart rate increased significantly after 4 weeks of eating the run-in diet. The cardiac diet group (n = 14) had larger increases in levels of cholesterol ( P = .001), triglycerides ( P = .02), eicosapentaenoic acid ( P < .001), docosahexaenoic acid ( P < .001), total omega-3 fatty acids ( P < .001), vitamin C ( P = 0.04), alpha-tocopherol ( P < .001), and gamma-tocopherol ( P < .001) compared to the placebo diet group (n = 15). The cardiac diet group also had larger reductions in maximal left-atrial dimension ( P = .003), left-ventricular internal dimension in diastole ( P = .03), and weight-based maximal left-atrial dimension ( P = .03).
Conclusions and Clinical Importance: Observed changes in both blood variables and echocardiographic measurements warrant additional studies on dietary modifications in dogs with early CVD.     

13.

Serum Serotonin Concentrations in Dogs with Degenerative Mitral Valve Disease     

J.W. Arndt  C.A. Reynolds  G.E. Singletary  J.M. Connolly  R.J. Levy  M.A. Oyama 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(6):1208-1213

Background: Increased serotonin (5HT) signaling has been implicated in valvular disease of humans and animals, including canine degenerative mitral valve disease (DMVD). High circulating 5HT concentration is a potential source of increased signaling, and serum 5HT concentrations have not been previously reported in dogs with DMVD.
Hypothesis: Dogs with DMVD and small breed dogs predisposed to DMVD have higher serum 5HT concentrations than large breed controls.
Animals: Fifty dogs affected with DMVD, 34 dogs predisposed to DMVD but without cardiac murmur or echocardiographic evidence of DMVD, and 36 healthy large breed control dogs.
Methods: Prospective analysis. Serum 5HT concentration was measured by an ELISA test.
Results: Median serum 5HT concentration was significantly higher in dogs with DMVD and in dogs predisposed to DMVD as compared with controls (DMVD, 765.5 ng/mL [interquartile range, 561.3–944.4]; predisposed, 774.9 ng/mL [528.3–1,026]; control, 509.8 ng/mL [320.8–708.8]; P = .0001). Subgroup analysis of predisposed dogs indicated significantly higher serum 5HT concentrations in Cavalier King Charles Spaniel (CKCS) dogs than in other breeds (CKCS, 855.0 ng/mL [635.8–1,088]; non-CKCS, 554.2 ng/mL [380.6–648.4]; P = .0023). Age, platelet count, and platelet morphology were not correlated with 5HT concentration in any group.
Conclusions and Clinical Importance: Dogs with DMVD had significantly higher serum 5HT concentrations when compared with large breed control dogs. Healthy CKCS dogs had significantly higher serum 5HT concentrations than other healthy dogs predisposed to DMVD. Additional investigation into a possible role of 5HT in the pathogenesis of DMVD is warranted.     

14.

Prothrombotic and Inflammatory Effects of Intravenous Administration of Human Immunoglobulin G in Dogs     

R. Tsuchiya  Y. Akutsu  A. Ikegami  M.A. Scott  S. Neo  T. Ishikawa  M. Hisasue  T. Yamada 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(6):1164-1169

Background: Intravenous administration of human immunoglobulin G (hIVIgG) has been suggested to potentiate thromboembolism in dogs, but supportive scientific reports are lacking.
Objectives: To determine if hIVIgG therapy promotes hypercoagulability and inflammation in dogs.
Animals: Twelve healthy Beagle dogs.
Methods: Prospective, experimental trial. An hIVIgG/saline solution was infused IV at 1 g/kg BW over 8 hours to 6 dogs, and physiological saline was infused to the other 6 dogs. Blood samples were drawn before, during, and after infusion for serial measurement of indicators of coagulation and inflammation. Data were analyzed by 2-way repeated measures analysis of variance.
Results: Dogs administered hIVIgG developed mildly decreased blood platelet concentrations without thrombocytopenia (median, 200 × 10³/μL; range, 150–302 × 10³/μL; P < .01), leukopenia (median, 3.5 × 10³/μL; range, 20–62 × 10³/μL; P < .001), and mildly increased plasma total protein concentrations (median, 6.3 g/dL; range, 5.6–6.7 g/dL; P < .001). Administration of hIVIgG was also associated with increases in fibrin/fibrinogen degradation products in all dogs (either 5 μg/mL or 10 μg/dL), thrombin-antithrombin III complexes (median, 7.2 ng/mL; range, 4.9–14.2 ng/mL; P < .001), and C-reactive protein concentrations (median, 2.5 mg/dL; range, 0.5–4.3 mg/dL; P < .01).
Conclusion and Clinical Importance: Administration of hIVIgG to dogs promotes hypercoagulability and an inflammatory state. This should be further evaluated and considered when using hIVIgG in dogs with IMHA or other prothrombotic conditions.     

15.

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.     

16.

Dietary Management of Hepatic Copper Accumulation in Labrador Retrievers     

G. Hoffmann  P.G. Jones  V. Biourge  T.S.G.A.M. van den Ingh  S.J. Mesu  P. Bode  J. Rothuizen 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(5):957-963

Background: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases.
Objectives: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations.
Animals: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations.
Methods: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo.
Results: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P < .001; group 2, P = .001) and at recheck 2 (n= 16; group 1, P = .03; group 2, P = .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment ( P = .65), at recheck 1 or at recheck 2 ( P = .52–.79).
Conclusions and Clinical Relevance: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.     

17.

Exacerbation of Hyperlactatemia by Infusion of Lactated Ringer''s Solution in Dogs With Lymphoma     

David M. Vail DVM    Gregory K. Ogilvie DVM    Martin J. Fettman DVM  PhD  Steven L. Wheeler DVM  MSy 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》1990,4(5):228-232

Blood lactate concentrations and acid-base status of six dogs with lymphoma were compared statistically with those from six healthy control dogs before, during, and after a 6-hour infusion of lactated Ringer's solution (LRS). Blood lactate concentrations in dogs with lymphoma were significantly (P less than 0.05) higher immediately before, and at the 1-, 2-, 4-, and 6-hour time periods after infusion when compared with controls. Blood lactate concentrations increased significantly (P = 0.016) after the first hour of infusion in dogs with lymphoma but did not increase in the control dogs. The increase in blood lactate concentrations over baseline values after 1 hour of LRS infusion was significantly (P = 0.008) greater in dogs with lymphoma when compared with controls. Blood lactate concentrations returned to baseline levels after 2 hours of infusion in dogs with lymphoma, suggesting that dogs with lymphoma have a transient inability to handle increased lactate loads when compared with controls. However, the potential to augment lactate use, clearance, or both is present and does occur over time. Blood gas values were not significantly altered within the lymphoma or control dog groups after 6 hours of LRS infusion. Blood bicarbonate concentrations in dogs with lymphoma were significantly decreased before and after LRS infusion when compared with controls.     

18.

Anemia Is Associated with Decreased Survival Time in Dogs with Lymphoma     

A.G. Miller  P.S. Morley  S. Rao  A.C. Avery  S.E. Lana  C.S. Olver 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(1):116-122

Background: Anemia is a common complication in human patients with neoplasia and has been associated with decreased survival time and a poorer quality of life.
Hypothesis: The presence of anemia at diagnosis is negatively associated with survival and remission times in dogs with lymphoma, but not in dogs with osteosarcoma.
Animals: Eighty-four dogs with lymphoma and 91 dogs with osteosarcoma that presented for treatment at the Animal Cancer Center, Colorado State University.
Methods: Retrospective, case-control study. Medical records were reviewed to determine the presence or absence of anemia (PCV < 40) at initial presentation. Median survival and remission times were identified by the Kaplan-Meier product limit method and the association between anemia and survival was determined by a multivariable Cox proportional hazard regression analysis.
Results: Cancer-related anemia is more frequent in dogs with lymphoma than in control dogs or dogs with osteosarcoma. Dogs with lymphoma and anemia had a significantly decreased survival time compared with dogs without anemia. There was no effect of anemia on remission time in dogs with lymphoma. Anemic dogs with osteosarcoma did not have decreased survival or remission time compared with nonanemic dogs with osteosarcoma.
Conclusions and Clinical Importance: Shortened survival time in dogs with lymphoma and anemia at initial presentation has important prognostic significance. Understanding cancer-related anemia in dogs might offer new opportunities to improve quality of life and survival times in these patients.     

19.

Monoclonal Antibody C219 Immunohistochemistry Against P-Glycoprotein: Sequential Analysis and Predictive Ability in Dogs With Lymphoma   总被引：1，自引：1，他引：0  

Philip J. Bergman DVM  MPH  MD    Gregory K. Ogilvie  Barbara E. Powers 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》1996,10(6):354-359

In the present study, the prevalence of positive staining for P-glycoprotein using C219 monoclonal antibody was assessed in 58 tissue samples of high-grade lymphoma from dogs before initiation of chemotherapy. Samples were also evaluated at relapse in 22 dogs, at necropsy in 34 dogs, and at all 3 times in 15 dogs. The frequency of positive staining was significantly higher than that found prior to the initiation of chemotherapy at the following times: relapse ( P = .0001), necropsy ( P < .0001), and both relapse and necropsy ( P < .001, sequential data). The frequency of positive staining prior to the initiation of chemotherapy was significantly inversely related to remission ( P < .001) and survival times ( P = .0012). Similarly, when populations below and above the median initial C219 score were compared with respect to remission and survival times, the population with scores greater than the median had significantly lower remission ( P < .001) and survival ( P = .008) times, respectively. The frequency of positive staining determined at relapse was significantly inversely related to the time from relapse to death ( P = .0102). Similarly, when populations below and above the median relapse C219 score were compared with respect to the time from relapse to death, the population with C219 scores greater than the median had a significantly lower time from relapse to death ( P = .006). It appears that this immunohistochemical methodology may be used as a predictor of remission time, survival time, and the time from relapse to death. Additional studies are required to confirm the usefulness of C219 as a true marker of P-glycoprotein and to evaluate P-glycoprotein as a useful prognostic factor in dogs with lymphoma.     

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Antioxidant status and biomarkers of oxidative stress in dogs with congestive heart failure     

Freeman LM  Rush JE  Milbury PE  Blumberg JB 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2005,19(4):537-541

Alterations in antioxidant status and oxidative stress have been documented in dogs with dilated cardiomyopathy (DCM). The purpose of this study was to more broadly assess this relationship in dogs with congestive heart failure (CHF). Malondialdehyde (MDA), 8-F(2alpha)-isoprostane, protein carbonyls, reduced (GSH) and oxidized (GSSG) glutathione, vitamins A, C, and E, and oxygen radical absorbance capacity (ORAC) were measured from a single venous blood sample from dogs with CHF secondary to DCM or chronic valvular disease (CVD) and in healthy controls. Nineteen dogs with CHF (14 CVD and 5 DCM) and 12 healthy controls were enrolled in the study. Concentrations of 8-F(2alpha)-isoprostane (CHF: 44.6 pg/mL [range, 27.1-98.0 pg/mL], controls: 25.3 pg/ mL [range, 11.1-80.4 pg/mL]) but not MDA (CHF: 4.11 microM [range, 1.89-6.39 microM], controls: 3.88 microM [range, 2.14-4.72 microM]) or protein carbonyls (0.69 nmol/mg protein [range, 0.37-1.67 nmol/mg protein], controls: 0.80 nmol/mg protein [range, 0.40-1.14 nmol/mg protein]) were significantly higher in the dogs with CHF than in the controls. Vitamin E concentration (CHF: 2,215 microg/ dL [range, 916-3,499 microg/dL], controls: 2,820 microg/dL [range, 1,738-3,775 microg/dL]) and GSH:GSSG (CHF: 12.0 [range, 3.69-30.1], controls: 22.7 [range, 12.5-227]) were significantly lower, whereas ORAC (CHF: 824 micromol Trolox equivalent/L [range, 304-984], controls: 497 micromol Trolox equivalent/L [range, 258-759]) and vitamin C (CHF: 0.90 mg/dL [range, 0.55-2.02 mg/dL], controls: 0.72 mg/dL [range, 0.43-0.85 mg/dL]) concentrations were higher in dogs with CHF than in controls. Vitamin A concentrations were not different between dogs with CHF and controls. No differences in any of the parameters were detected between dogs with DCM versus those with CVD. Some antioxidant defenses are decreased in dogs with CHF, and some biomarkers of oxidative stress are increased in dogs with CHF. The effect of dietary interventions to correct this imbalance in antioxidant defenses warrants further study.     

Efficacy of Combination Chemotherapy for Treatment of Gastrointestinal Lymphoma in Dogs

Background: Chemotherapy for multicentric canine lymphoma has favorable results. The gastrointestinal (GI) tract is the most common extranodal site of canine lymphoma, but there have been no prospective studies to determine outcome when dogs with GI lymphoma are treated with chemotherapy.
Hypothesis: Treatment with a multiagent chemotherapy protocol is associated with a poor outcome in dogs with GI lymphoma.
Animals: Eighteen dogs with histologically confirmed GI lymphoma.
Methods: Prospective clinical trial in which dogs with GI lymphoma were treated with a 20-week combination chemotherapy protocol consisting of induction and consolidation phases.
Results: Thirteen dogs had primary GI lymphoma and 5 had multicentric lymphoma with GI involvement. The majority of the lymphomas (63%) were of T-cell origin. Overall remission rate was 56%; 9 dogs achieved a complete remission for a median of 86 days (range, 22–420 days) and 1 dog achieved a partial remission for 26 days. Overall median survival time was 77 days (range, 6–700 days). Dogs that failed to achieve a remission (10 versus 117 days; P = .002) or had diarrhea at initial presentation (70 versus 700 days; P < .001) had shorter survival times.
Conclusion and Clinical Importance: The response and survival of dogs with GI lymphoma treated with multiagent chemotherapy is poor but long-term survival is possible.     

Serial determination of biomarkers of oxidative stress and antioxidant status in dogs with naturally occurring gastric dilatation-volvulus

Objective: To serially determine the biomarkers of oxidative stress and antioxidant status of dogs with gastric dilatation‐volvulus (GDV) over 48 hours. Design: Prospective study. Setting: Veterinary teaching hospital intensive care unit. Animals: Thirteen client‐owned dogs with GDV. Interventions: None. Measurement and main results: For all dogs, biomarkers of oxidative stress and antioxidant status were ascertained. Indicators of oxidative stress measured included F_2α‐isoprostanes (isoprostanes) and malondialdehyde (MDA). Vitamin C, vitamin E, glutathione peroxidase (GSHPx), and oxygen radical absorbance capacity (ORAC) were measured to assess antioxidant status. Oxidants and antioxidants were measured at the time of admission and at 24 and 48 hours post‐admission. There were significant decreases in vitamin E (P=0.002), vitamin C (P=0.001), ORAC (P=0.02), and MDA (P=0.001) during hospitalization. There was no significant change in GSHPx and isoprostane concentrations over time. Conclusion: Oxidative stress and antioxidant capacity in dogs with GDV change over time. Further studies measuring oxidative stress in more severely affected dogs and performing measurements earlier in the disease process may be beneficial in determining when oxidative stress is most severe during the course of GDV management.     

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.     

An hGM‐CSF DNA‐Cationic Lipid Complexed Autologous Tumor Cell Vaccine did not Improve Remission Duration in Dogs with Lymphoma

Introduction:  Lymphoma is one of the most common cancers in dogs and while clinical remission can be induced using chemotherapy, very few dogs are cured. Since cytokine‐adjuvanted autologous whole‐tumor‐cell vaccines (ATCV) can induce potent antitumor immune responses against otherwise non‐immunogenic cancers we initiated a study of such an approach in dogs with lymphoma.
Methods:  Following achievement of a complete remission using a 19‐week CHOP‐based chemotherapy protocol, 51 dogs with B‐cell lymphoma were randomized to receive 8 treatments (4 weekly, then 4 additional at q2wk intervals) of vaccine or lipid‐equivalent placebo. Dogs were followed monthly for assessment of remission duration and survival. Surrogate indices of immune response (delayed‐type hypersensitivity, interferon‐γ quantitative RT‐PCR, lymphocyte proliferation, and flow cytometry for lymphoma‐specific antibodies) were also investigated before and after vaccination.
Results:  No significant difference in median remission duration was observed between dogs receiving vaccine (277 days) or placebo (258 days); the Kaplan‐Meier curves were virtually super‐imposable. No significant differences in surrogate indices of immune response were noted pre‐ and post‐vaccination.
Conclusions:  In this context, an hGM‐CSF DNA‐cationic lipid complexed ATCV vaccine did not enhance remission duration in dogs with lymphoma, likely due to lack of vaccine‐induced tumor‐specific immunity.     

Serum C-reactive protein concentration as an indicator of remission status in dogs with multicentric lymphoma

BACKGROUND: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. OBJECTIVE: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. ANIMALS: Twenty-two dogs with untreated multicentric lymphoma. METHODS: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. RESULTS: Before therapy, a statistically significant majority of the dogs (P = .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P < .001). CRP concentrations of dogs in complete remission (median, 1.91; range, 0.2-103) were significantly different (P = .031) from those of dogs with partial remission (median, 2.48; range, 0-89), stable disease (median, 1.77; range, 1.03-42.65), or progressive disease (median, 8.7; range, 0-82.5). There was profound variation of CRP measurements within each dog. CONCLUSIONS: CRP is useful in determining complete remission status after treatment with cytotoxic drugs. However, the individual variation between dogs means CRP concentration is not sufficiently different in other remission states to permit its use in monitoring progression of the disease. Greater reliability in determining remission status might be achieved by combining CRP concentration with other serum markers.     

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.     

Alterations in Lipoprotein Profiles in Dogs With Lymphoma

After a 12-hour fast, blood samples were obtained from 31 dogs with previously untreated lymphoma. Blood samples were also collected from 16 of these dogs after up to 5 treatments with doxorubicin (30 mg/m² intravenously every 3 weeks). All 16 dogs underwent complete remission. Five dogs were re-evaluated after relapse and after overt signs of cancer cachexia had become clinically apparent. Samples were assayed for 8 quantitative parameters: total cholesterol (T-CH) and total triglyceride (T-TG) concentrations, and the concentration of cholesterol and triglyceride in each of the three major lipoprotein fractions, very-low-density lipoprotein (VLDL-CH and VLDL-TG), low-density lipoprotein (LDL-CH and LDL-TG), and high-density lipoprotein (HDL-CH and HDL-TG). The results were compared with those from 20 healthy control dogs of similar weight and age before and 3 weeks after being given one dose of doxorubicin (30 mg/m² intravenously). The administration of doxorubicin to control dogs resulted in a significant (P> .05) decrease in T-CH, LDL-CH, and HDL-CH, as well as a significant increase in VLOL-TG and HDL-TG. When compared with untreated controls, untreated dogs with lymphoma had significantly higher concentrations of VLDL-CH, T-TG, VLDL-TG, LDL-TG, and HDL-TG, and significantly lower concentrations of HDL-CH. HDL-TG and VLDL-TG concentrations from dogs with lymphoma were significantly increased above pretreatment values after relapse and development of overt signs of cancer cachexia. Dogs in remission that were evaluated after one dose of doxorubicin had significantly higher concentrations of T-CH, VLDL-CH, T-TG, and LDL-TG when compared with controls that were evaluated after an identical dose of doxorubicin. HDL-TG increased significantly over pretreatment values in dogs with lymphoma after doxorubicin therapy. These results suggest that dogs with lymphoma have significant alterations in lipid profiles, and with the possible exception of HDL-CH, these abnormalities do not normalize when clinical remission is obtained.     

Effects of dietary modification in dogs with early chronic valvular disease

Background:The potential benefits of nutritional modification in early canine cardiac disease are not known.
Hypothesis:We hypothesized that echocardiographic, neuroendocrine, and nutritional variables will differ between dogs with asymptomatic chronic valvular disease (CVD) and healthy controls, and that a moderately reduced sodium diet enriched with antioxidants, n-3 fatty acids, taurine, carnitine, and arginine will alter these variables in dogs with CVD.
Methods: Echocardiography was performed and blood was collected. After baseline comparison with healthy controls, all dogs with CVD were fed a low-sodium run-in diet for 4 weeks, reevaluated, and then randomized to receive either the cardiac diet or a placebo diet for 4 weeks.
Results: At baseline, dogs with CVD (n = 29) had significantly lower circulating sodium, chloride, arginine, and methionine concentrations and higher plasma concentrations of atrial natriuretic peptide compared to healthy controls. In dogs with CVD, plasma aldosterone concentration and heart rate increased significantly after 4 weeks of eating the run-in diet. The cardiac diet group (n = 14) had larger increases in levels of cholesterol ( P = .001), triglycerides ( P = .02), eicosapentaenoic acid ( P < .001), docosahexaenoic acid ( P < .001), total omega-3 fatty acids ( P < .001), vitamin C ( P = 0.04), alpha-tocopherol ( P < .001), and gamma-tocopherol ( P < .001) compared to the placebo diet group (n = 15). The cardiac diet group also had larger reductions in maximal left-atrial dimension ( P = .003), left-ventricular internal dimension in diastole ( P = .03), and weight-based maximal left-atrial dimension ( P = .03).
Conclusions and Clinical Importance: Observed changes in both blood variables and echocardiographic measurements warrant additional studies on dietary modifications in dogs with early CVD.     

Serum Serotonin Concentrations in Dogs with Degenerative Mitral Valve Disease

Background: Increased serotonin (5HT) signaling has been implicated in valvular disease of humans and animals, including canine degenerative mitral valve disease (DMVD). High circulating 5HT concentration is a potential source of increased signaling, and serum 5HT concentrations have not been previously reported in dogs with DMVD.
Hypothesis: Dogs with DMVD and small breed dogs predisposed to DMVD have higher serum 5HT concentrations than large breed controls.
Animals: Fifty dogs affected with DMVD, 34 dogs predisposed to DMVD but without cardiac murmur or echocardiographic evidence of DMVD, and 36 healthy large breed control dogs.
Methods: Prospective analysis. Serum 5HT concentration was measured by an ELISA test.
Results: Median serum 5HT concentration was significantly higher in dogs with DMVD and in dogs predisposed to DMVD as compared with controls (DMVD, 765.5 ng/mL [interquartile range, 561.3–944.4]; predisposed, 774.9 ng/mL [528.3–1,026]; control, 509.8 ng/mL [320.8–708.8]; P = .0001). Subgroup analysis of predisposed dogs indicated significantly higher serum 5HT concentrations in Cavalier King Charles Spaniel (CKCS) dogs than in other breeds (CKCS, 855.0 ng/mL [635.8–1,088]; non-CKCS, 554.2 ng/mL [380.6–648.4]; P = .0023). Age, platelet count, and platelet morphology were not correlated with 5HT concentration in any group.
Conclusions and Clinical Importance: Dogs with DMVD had significantly higher serum 5HT concentrations when compared with large breed control dogs. Healthy CKCS dogs had significantly higher serum 5HT concentrations than other healthy dogs predisposed to DMVD. Additional investigation into a possible role of 5HT in the pathogenesis of DMVD is warranted.     

Prothrombotic and Inflammatory Effects of Intravenous Administration of Human Immunoglobulin G in Dogs

Background: Intravenous administration of human immunoglobulin G (hIVIgG) has been suggested to potentiate thromboembolism in dogs, but supportive scientific reports are lacking.
Objectives: To determine if hIVIgG therapy promotes hypercoagulability and inflammation in dogs.
Animals: Twelve healthy Beagle dogs.
Methods: Prospective, experimental trial. An hIVIgG/saline solution was infused IV at 1 g/kg BW over 8 hours to 6 dogs, and physiological saline was infused to the other 6 dogs. Blood samples were drawn before, during, and after infusion for serial measurement of indicators of coagulation and inflammation. Data were analyzed by 2-way repeated measures analysis of variance.
Results: Dogs administered hIVIgG developed mildly decreased blood platelet concentrations without thrombocytopenia (median, 200 × 10³/μL; range, 150–302 × 10³/μL; P < .01), leukopenia (median, 3.5 × 10³/μL; range, 20–62 × 10³/μL; P < .001), and mildly increased plasma total protein concentrations (median, 6.3 g/dL; range, 5.6–6.7 g/dL; P < .001). Administration of hIVIgG was also associated with increases in fibrin/fibrinogen degradation products in all dogs (either 5 μg/mL or 10 μg/dL), thrombin-antithrombin III complexes (median, 7.2 ng/mL; range, 4.9–14.2 ng/mL; P < .001), and C-reactive protein concentrations (median, 2.5 mg/dL; range, 0.5–4.3 mg/dL; P < .01).
Conclusion and Clinical Importance: Administration of hIVIgG to dogs promotes hypercoagulability and an inflammatory state. This should be further evaluated and considered when using hIVIgG in dogs with IMHA or other prothrombotic conditions.     

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.     

Dietary Management of Hepatic Copper Accumulation in Labrador Retrievers

Background: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases.
Objectives: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations.
Animals: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations.
Methods: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo.
Results: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P < .001; group 2, P = .001) and at recheck 2 (n= 16; group 1, P = .03; group 2, P = .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment ( P = .65), at recheck 1 or at recheck 2 ( P = .52–.79).
Conclusions and Clinical Relevance: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.     

Exacerbation of Hyperlactatemia by Infusion of Lactated Ringer''s Solution in Dogs With Lymphoma

Blood lactate concentrations and acid-base status of six dogs with lymphoma were compared statistically with those from six healthy control dogs before, during, and after a 6-hour infusion of lactated Ringer's solution (LRS). Blood lactate concentrations in dogs with lymphoma were significantly (P less than 0.05) higher immediately before, and at the 1-, 2-, 4-, and 6-hour time periods after infusion when compared with controls. Blood lactate concentrations increased significantly (P = 0.016) after the first hour of infusion in dogs with lymphoma but did not increase in the control dogs. The increase in blood lactate concentrations over baseline values after 1 hour of LRS infusion was significantly (P = 0.008) greater in dogs with lymphoma when compared with controls. Blood lactate concentrations returned to baseline levels after 2 hours of infusion in dogs with lymphoma, suggesting that dogs with lymphoma have a transient inability to handle increased lactate loads when compared with controls. However, the potential to augment lactate use, clearance, or both is present and does occur over time. Blood gas values were not significantly altered within the lymphoma or control dog groups after 6 hours of LRS infusion. Blood bicarbonate concentrations in dogs with lymphoma were significantly decreased before and after LRS infusion when compared with controls.     

Anemia Is Associated with Decreased Survival Time in Dogs with Lymphoma

Background: Anemia is a common complication in human patients with neoplasia and has been associated with decreased survival time and a poorer quality of life.
Hypothesis: The presence of anemia at diagnosis is negatively associated with survival and remission times in dogs with lymphoma, but not in dogs with osteosarcoma.
Animals: Eighty-four dogs with lymphoma and 91 dogs with osteosarcoma that presented for treatment at the Animal Cancer Center, Colorado State University.
Methods: Retrospective, case-control study. Medical records were reviewed to determine the presence or absence of anemia (PCV < 40) at initial presentation. Median survival and remission times were identified by the Kaplan-Meier product limit method and the association between anemia and survival was determined by a multivariable Cox proportional hazard regression analysis.
Results: Cancer-related anemia is more frequent in dogs with lymphoma than in control dogs or dogs with osteosarcoma. Dogs with lymphoma and anemia had a significantly decreased survival time compared with dogs without anemia. There was no effect of anemia on remission time in dogs with lymphoma. Anemic dogs with osteosarcoma did not have decreased survival or remission time compared with nonanemic dogs with osteosarcoma.
Conclusions and Clinical Importance: Shortened survival time in dogs with lymphoma and anemia at initial presentation has important prognostic significance. Understanding cancer-related anemia in dogs might offer new opportunities to improve quality of life and survival times in these patients.     

Monoclonal Antibody C219 Immunohistochemistry Against P-Glycoprotein: Sequential Analysis and Predictive Ability in Dogs With Lymphoma

In the present study, the prevalence of positive staining for P-glycoprotein using C219 monoclonal antibody was assessed in 58 tissue samples of high-grade lymphoma from dogs before initiation of chemotherapy. Samples were also evaluated at relapse in 22 dogs, at necropsy in 34 dogs, and at all 3 times in 15 dogs. The frequency of positive staining was significantly higher than that found prior to the initiation of chemotherapy at the following times: relapse ( P = .0001), necropsy ( P < .0001), and both relapse and necropsy ( P < .001, sequential data). The frequency of positive staining prior to the initiation of chemotherapy was significantly inversely related to remission ( P < .001) and survival times ( P = .0012). Similarly, when populations below and above the median initial C219 score were compared with respect to remission and survival times, the population with scores greater than the median had significantly lower remission ( P < .001) and survival ( P = .008) times, respectively. The frequency of positive staining determined at relapse was significantly inversely related to the time from relapse to death ( P = .0102). Similarly, when populations below and above the median relapse C219 score were compared with respect to the time from relapse to death, the population with C219 scores greater than the median had a significantly lower time from relapse to death ( P = .006). It appears that this immunohistochemical methodology may be used as a predictor of remission time, survival time, and the time from relapse to death. Additional studies are required to confirm the usefulness of C219 as a true marker of P-glycoprotein and to evaluate P-glycoprotein as a useful prognostic factor in dogs with lymphoma.     

Antioxidant status and biomarkers of oxidative stress in dogs with congestive heart failure

Alterations in antioxidant status and oxidative stress have been documented in dogs with dilated cardiomyopathy (DCM). The purpose of this study was to more broadly assess this relationship in dogs with congestive heart failure (CHF). Malondialdehyde (MDA), 8-F(2alpha)-isoprostane, protein carbonyls, reduced (GSH) and oxidized (GSSG) glutathione, vitamins A, C, and E, and oxygen radical absorbance capacity (ORAC) were measured from a single venous blood sample from dogs with CHF secondary to DCM or chronic valvular disease (CVD) and in healthy controls. Nineteen dogs with CHF (14 CVD and 5 DCM) and 12 healthy controls were enrolled in the study. Concentrations of 8-F(2alpha)-isoprostane (CHF: 44.6 pg/mL [range, 27.1-98.0 pg/mL], controls: 25.3 pg/ mL [range, 11.1-80.4 pg/mL]) but not MDA (CHF: 4.11 microM [range, 1.89-6.39 microM], controls: 3.88 microM [range, 2.14-4.72 microM]) or protein carbonyls (0.69 nmol/mg protein [range, 0.37-1.67 nmol/mg protein], controls: 0.80 nmol/mg protein [range, 0.40-1.14 nmol/mg protein]) were significantly higher in the dogs with CHF than in the controls. Vitamin E concentration (CHF: 2,215 microg/ dL [range, 916-3,499 microg/dL], controls: 2,820 microg/dL [range, 1,738-3,775 microg/dL]) and GSH:GSSG (CHF: 12.0 [range, 3.69-30.1], controls: 22.7 [range, 12.5-227]) were significantly lower, whereas ORAC (CHF: 824 micromol Trolox equivalent/L [range, 304-984], controls: 497 micromol Trolox equivalent/L [range, 258-759]) and vitamin C (CHF: 0.90 mg/dL [range, 0.55-2.02 mg/dL], controls: 0.72 mg/dL [range, 0.43-0.85 mg/dL]) concentrations were higher in dogs with CHF than in controls. Vitamin A concentrations were not different between dogs with CHF and controls. No differences in any of the parameters were detected between dogs with DCM versus those with CVD. Some antioxidant defenses are decreased in dogs with CHF, and some biomarkers of oxidative stress are increased in dogs with CHF. The effect of dietary interventions to correct this imbalance in antioxidant defenses warrants further study.