Endotoxemia and Tumor Necrosis Factor Activity in Dogs With Naturally Occurring Parvoviral Enteritis

A prospective, nonrandomized study was performed to evaluate the role of endotoxin and tumor necrosis factor (TNF) in dogs with parvoviral enteritis. Seventeen dogs with naturally occurring parvoviral enteritis were enrolled in the study. Plasma samples were obtained for quantification of endotoxin and TNF on presentation and at 3 and 6 hours after therapy with either fluids prior to antibiotics, or fluids concurrently with antibiotics. All dogs received standard supportive therapy. Fourteen of 17 dogs had endotoxin in their plasma during the study period; 7 of 17 dogs had measurable TNF. No endotoxin or TNF was detectable in plasma from normal puppies. An increase in TNF activity was pre dictive of mortality ( P = .041). There was a trend for increasing endotoxin activity to predict mortality ( P = .0769). Animals that received antibiotics with fluids were significantly older than those that received fluids prior to antibiotics, and there was a trend for animals that received antibiotics with fluids to have a decrease in endotoxin activity after treatment ( P = .054). Endotoxin and activation of the cytokine cascade are integral to the pathophysiology of parvoviral enteritis. Measures to limit endotoxemia and the systemic inflammatory response may improve survival.     

Efficacy of Minocycline in Naturally Occurring Nonacute Ehrlichia canis Infection in Dogs

Background

Minocycline has been used in the treatment of Ehrlichia canis infection in dogs as an alternative to doxycycline, the recommended treatment. However, efficacy of this alternative therapy is unknown.

Objective

To assess the efficacy of minocycline in the treatment of natural occurring E. canis infection in dogs.

Animals

Ten privately owned dogs of mixed breed positive for E. canis by blood PCR.

Methods

Prospective, randomized clinical study. Dogs positive for E. canis by PCR were housed in a kennel environment and randomly allocated to receive doxycycline 10 mg/kg bodyweight PO once daily (“gold standard” control group) or minocycline (extralabel) 10 mg/kg bodyweight PO twice daily (treatment test group) for 28 days. Blood, analyzed by PCR to determine the presence or absence of E. canisDNA, was collected weekly during treatment starting on the first day of treatment and including through day 35, 7 days after the last treatment.

Results

In both groups, one dog tested negative after 7 days of treatment. For the doxycycline group, the latest time to a negative PCR test was after 3 weeks of treatment. For the minocycline group, the latest time was on day 28 of treatment. All dogs tested negative 7 days after the end of treatment.

Conclusion and Clinical Importance

Minocycline can be an effective alternative to doxycycline for clearing E. canis from the blood in nonacute infections.     

Monoclonal Gammopathy Associated With Naturally Occurring Canine Ehrlichiosis

Clinical, hematologic, and immunologic findings for 14 dogs with Ehrlichia canis monoclonal gammopathy were studied retrospectively. Epistaxis, anemia, thrombocytopenia, hypoalbuminemia, hypergammaglobulinemia, and proteinuria were documented in the majority of these dogs. The serum protein electrophoresis pattern was characterized by a distinct narrow-base monoclonal spike, by a broad-base monoclonal spike, or by a monoclonal spike superimposed on a polyclonal gammopathy. The monoclonal spike disappeared following tetracycline treatment for ehrlichiosis. The long-term prognosis following treatment was generally good. The diagnostic features of monoclonal gammopathy due to myeloma were compared with those of E. canis monoclonal gammopathy. Owing to numerous similarities in clinical, hematologic, and immunologic findings, we conclude that an E. canis antibody titer should be determined in all dogs in which a diagnosis of benign monoclonal gammopathy is contemplated or definitive evidence of myeloma, leukemia, or macroglobulinemia is lacking.     

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

Background

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

Hypothesis/Objectives

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

Animals

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

Methods

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

Results

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

Conclusions and Clinical Importance

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

Naturally Occurring Scrapie in Southdown Sheep

The purpose of this study was to characterize naturally occurring scrapie in the Southdown breed of sheep. Experimental subjects included 4 Southdown ewes admitted to the University of Missouri, College of Veterinary Medicine Large Animal Clinic. All 4 sheep had signs compatible with clinical scrapie. Cerebrospinal fluid (CSF) cell counts ranged from a low of 1 nucleated cell/microL to high of 4 cells/microL with a median of 3 cells/microL. Cerebrospinal protein concentrations ranged from 26 to 78 mg/dL with a median of 53 mg/dL. Immunoassay of the CSF for the 14-3-3 protein yielded positive results in 3 of the 4 sheep. Sequencing of the prion protein (PrP) gene revealed that all 4 sheep were homozygous for glutamine at codon 171 and, hence, were of the QQ genotype. Histopathologic examination of brain stem tissue sections revealed intracytoplasmic neuronal vacuolation and mild spongiform changes in the gray matter neuropil in all 4 ewes. The diagnosis of scrapie was confirmed by immunohistochemical staining for the abnormal PrP Our results suggest that the genetics of scrapie susceptibility are probably similar in Suffolk and Southdown sheep. Positive immunoassay results for the 14-3-3 protein were observed in 3 of the 4 sheep.     

Familial Glomerulonephritis in Doberman Pinscher Dogs

Progressive renal disease in 13 related Doberman pinscher dogs had the histological criteria of membranoproliferative glomerulonephritis. Polyuria, polydipsia and weight loss were the usual initial abnormalities and were observed at one year of age or less in seven of 11 dogs diagnosed antemortem as having renal disease. There was no sex predilection. All dogs were traced to a common male dog no more than four generations previously.     

Naturally Occurring Histoplasmosis in Guinea Pigs

Histoplasmosis naturally occurring in laboratory guinea pigs is described in its clinical, necropsy, histological and mycological aspects.

The animals if adult show a chronic disease with progressive emaciation and lameness of the hind legs. The young below three months of age died in 2 to 4 weeks presenting ruffled fur, great dorsal curvature and sometimes closed eyelids and catarrhal conjunctivitis.

At necropsy the principal lesions were ulcerative gastritis, hemorrhagic and catarrhal enteritis, enlarged spleen and mesenteric lymph nodes. Sometimes the liver, lungs, mediastinal lymph nodes and other organs showed lesions.

Histological and mycological demonstration of the fungus completed the diagnosis and the surviving animals were burned and sanitation measures instituted.

Histological evidence of histoplasmosis in a cow's lung from the area from which the grass was obtained for the feeding of the guinea pigs suggests an epidemiological link. Efforts will be made to isolate and demonstrate H. capsulatum in wild animals on the same area.

     

Efficacy of Azathioprine Versus Cyclosporine on Kidney Graft Survival in Transfused and Nontransfused Ummatched Mongrel Dogs

Sixteen mongrel dogs had bilateral nephrectomy and received a renal allograft from an unmatched mongrel. One group of eight dogs was treated orally with azathioprine and prednisone; another group of eight dogs was treated orally with cyclosporine and prednisone. Four dogs of each group received four blood transfusions each prior to surgery. Mean survival time was nearly the same in the azathioprine-treated and the cyclosporine-treated dogs. Transfusions prolonged survival in the azathioprine-treated group but not in the cyclosporine-treated group. Retrospective measurement of whole blood trough cyclosporine concentrations indicated marked variation between dogs and in the same dog at different times. This variation may have influenced graft survival. Only one dog survived the 9-month period of observation, indicating that refinements of the techniques used in this study will be required for long-term survival of renal allografts in unrelated mongrel dogs.     

Efficacy of Spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve Disease

Background: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. Hypothesis: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). Animals: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). Methods: Double‐blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac‐related death, euthanasia, or severe worsening of MR. Results: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22–0.90; log rank test, P= .017). Risk of cardiac‐ related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13–0.76; P= .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). Conclusion and Clinical Importance: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac‐related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.     

Serial Estimation of Survival Prediction Indices Does Not Improve Outcome Prediction in Critically III Dogs with Naturally Occurring Disease

Objective: The objectives of this study were to test the value of adding serial measurements to the Survival Prediction Index (SPI 2), and to investigate whether time trajectories add predictive information beyond measurements at a single point in time.
Design: Prospective clinical trial.
Setting: Intensive care unit at a Veterinary Teaching Hospital.
Animals: 63 critically ill dogs
Interventions: Physiologic data were collected within 24 hours of admission to the ICU (Day 1), and again on Day 3 of hospitalization.
Measurements: The first analysis applied the SPI 2 equation on Day 1 and again on Day3. Then a prediction model was re-estimated using Day 1 measurements, and the incremental predictive value of adding Day 1 to Day 3 change scores was evaluated. the third analysis tested the incremental predictive value of change scores in models containing only one prognostic variable. The final analysis compared the re-estimated Day 1 model to an analogously re-estimated Day 3 model.
Main Results: Using the SPI 2 equation, the AUC was 7.7% higher using Day 3 measurements than that obtained using Day 1 measurements (P = 0.515). Starting with the re-estimated Day 1 model (AUC = 0.925), forward stepwise addition of the difference score for each variable did not result in an improvement in the AUC. The AUC for the re-estimated Day 1 model was not statistially different from that of the re-estimated model using Day 3 measurements.
Conculusion: This study shows no benefit to repeated calculation of the SPI 2 later in hospitalization.     

An Investigation of the Action of Neutral Protamine Hagedorn Human Analogue Insulin in Dogs with Naturally Occurring Diabetes Mellitus

Background: Neutral Protamine Hagedorn human analogue insulin (Humulin N) is commonly used for treatment of canine diabetes mellitus (DM). However, blood glucose and serum insulin concentrations in Humulin N-treated dogs with naturally occurring DM have not been reported.
Objective: To investigate blood glucose and serum insulin concentrations in the clinical setting of client-owned Humulin N-treated dogs with naturally occurring, well-regulated DM.
Animals: Ten client-owned dogs with naturally occurring, well-regulated DM.
Methods: In this clinical study, blood glucose and serum insulin concentrations were measured when dogs received food and insulin (T₀), at approximately every half hour for the next 2 hours, and then approximately every 2 hours for an additional 8 hours. Insulin duration of action was defined as the number of hours from T₀ to the lowest blood glucose concentration and until blood glucose concentration returned to an interpolated value of 70% of basal blood glucose concentration (Glucose_b).
Results: Mean percent of insulin-induced blood glucose suppression was 49.9 ± 17.1% (median, 46%; range, 29–78%). Insulin duration of action ranged from 4 to 10 hours. Blood glucose concentration increased initially and returned to Glucose_b within 0.6–2.2 hours after T₀ in 5 dogs. This initial blood glucose surge then was followed by blood glucose suppression in all 5 dogs.
Conclusions and Clinical Importance: These results suggest that Humulin N administered SC twice daily is an effective mode of treatment for dogs with naturally occurring DM. Postprandial hyperglycemia is present in some well-regulated diabetic dogs treated with Humulin N.     

Naturally Occurring Acute Coliform Mastitis in Holstein Cattle

Physical examination and clinicopathologic findings from 44 adult Holstein cows with naturally occurring coliform mastitis were studied. The cattle were grouped for comparison by stage of lactation and survival. Cattle within the first 4 weeks of lactation maintained higher median mature neutrophil counts (1,200 versus 300/μL) in peripheral blood than cattle later in lactation. Nonsurviving cows had higher median creatinine concentration (2.5 versus 1.6 mg/dL) and anion gap (25 versus 20 mEq/L), and lower serum protein (7.1 versus 7.6 gm/dL) and total CO₂ (19.8 versus 25 mEq/L) concentrations than surviving cows (P < .05). These findings indicate that cattle with uremia and metabolic acidosis are less likely to survive the infection. Bacteriologic blood cultures were performed on 34 of the 44 cows studied. Esche-richia coli was isolated from the blood in 11 (32%) cows. Clinical presentation and clinicopathologic data were compared in bacteremic versus nonbacteremic cows to evaluate these data as predictors of bacteremia. Bacteremic cows were sick longer prior to admission (2 versus 1 days), maintained higher median counts of total nucleated cells (6.6 versus 2.4 × 10³ cells/μL), myelocytes (0.2 versus 0 × 10³ cells/μL), metamyelocytes (0.5 versus 0.02 × 10³ cells/μL), band neutrophils (0.7 versus 0.1 × 10³ cells/μL), and lymphocytes (2.1 versus 1.4 × 10³ cells/μL) than nonbacteremic cows, and had higher plasma fibrinogen concentration (600 versus 500 mg/dL) (P < .05). There were no differences between the physical or serum biochemical measurements. Four of 11 bacteremic cows and 5 of 23 nonbacteremic cows died or were euthanized (P > .05). The high prevalence of bacteremia seen in cows with coliform mastitis has not been reported previously, and may have been due to the duration of disease, severity of signs, or culture technique. These findings suggest that systemic antibiotic therapy may be beneficial in some severe cases of coliform mastitis. J Vet Intern Med 1996;252–257. Copyright©1996 by the American College of Veterinary Internal Medicine.     

Early Tumor Response to Intraarterial or Intravenous Administration of Carboplatin to Treat Naturally Occurring Lower Urinary Tract Carcinoma in Dogs

Background

Survival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.

Objective

To describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).

Animals

Client‐owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).

Methods

Retrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.

Results

Intraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).

Conclusion and Clinical Importance

This study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow‐up time was short and the impact on long‐term outcome and survival was not determined.