A retrospective multi‐center study of treatment,outcome, and prognostic factors in 34 dogs with disseminated aspergillosis in Australia

BackgroundDisseminated aspergillosis (DA) in dogs has a guarded prognosis and there is a lack of a gold standard treatment protocol.ObjectiveTo retrospectively assess survival times and factors influencing survival times.AnimalsDogs diagnosed with DA from January 2007 to June 2017.MethodsDisseminated aspergillosis case data were retrieved from 13 Australian veterinary referral centers, with a diagnosis confirmed with culture or PCR. Factors influencing survival time after diagnosis were quantified using a Cox proportional hazards regression model.ResultsThirty‐four dogs met the study inclusion criteria. Twenty‐two dogs were treated with antifungal treatment and 12 dogs received no antifungal treatment. Accounting for censoring of dogs that were either still alive on the date of data collection or were loss to follow‐up, dogs treated with itraconazole alone (n = 8) had a median survival time (MST) of 63 (95% CI: 20−272) days compared to 830 (95% CI: 267‐1259) days for the n = 14 dogs that received multimodal antifungal therapy (χ2 test statistic 8.6; df = 1; P < .01). The daily hazard of death (DHOD) for dogs with abnormally high serum creatinine concentration at the time of diagnosis was 7.4 (95% CI: 1.9‐29) times that of dogs with serum creatinine within the reference interval.Conclusion and Clinical ImportanceSerum creatinine concentration at the time of diagnosis is a useful prognostic indicator for survival after a diagnosis of DA. The MST for dogs treated with multimodal antifungal therapy is longer than itraconazole alone and warrant further investigation (P < .01).     

Clinical features of canine granulocytic anaplasmosis in 18 naturally infected dogs

BACKGROUND: Anaplasma phagocytophilum, the causative agent of canine granulocytic anaplasmosis (CGA), is a Gram-negative intracellular organism transmitted by ixodid ticks. Thus far, only a few clinical studies evaluating dogs with CGA have been published. OBJECTIVES: Evaluation of dogs naturally infected with A. phagocytophilum in which known co-infections were excluded. ANIMALS: Eighteen dogs with CGA. METHODS: Prospective study. The diagnosis of CGA was based on a positive PCR test result; dogs with co-infections were excluded. History, clinical findings, CBC, clinical biochemistry, infectious disease screening, diagnostic imaging, and the course of disease were evaluated. RESULTS: CGA was diagnosed based on a positive PCR test for A. phagocytophilum; 10 dogs also had morulae in neutrophils. Six of 18 dogs were seronegative to A. phagocytophilum, the others were seropositive. All dogs were acutely ill. The most common clinical findings were lethargy, inappetence, fever, and splenomegaly. Abnormal laboratory results included thrombocytopenia, anemia, lymphopenia, hypoalbuminemia, and abnormally high plasma alkaline phosphatase activity. In 6 of 10 dogs tested, the platelet-bound antibody test was positive; Coombs' test was negative in 9 dogs. All dogs were treated with doxycycline and recovered. PCR testing as well as blood smear analysis for morulae were negative in 14 tested dogs 2-8 weeks after beginning treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical findings in dogs with CGA were nonspecific. Positive platelet-bound antibody test results suggest immune-mediated platelet destruction as an important pathogenic mechanism. With correct diagnosis and treatment, prognosis is good.     

Detection of serum alpha-fetoprotein in dogs with naturally occurring malignant neoplasia

Serum alpha-fetoprotein (AFP) concentrations were determined, by use of an automated microparticle enzyme-linked immunoassay (MEIA), in 16 control dogs and 48 dogs with previously untreated, histologically confirmed, naturally occurring neoplasia (17 dogs with lymphoma and 31 dogs with nonhematopoietic malignancies, 13 dogs with carcinomas, 18 dogs with sarcomas). Mean serum AFP concentrations for untreated dogs with lymphoma, for dogs with sarcomas, and for dogs with carcinomas were not significantly different from the mean serum AFP concentration for the 16 untreated control dogs. Mean serum AFP concentration for dogs with transitional cell carcinoma (n=7) was not significantly different from the mean serum AFP concentration for the control dogs. It has been shown previously by others that a mean serum AFP concentration > 225 ng/mL is suggestive of a hepatic malignancy (e.g., hepatocellular carcinoma, lymphoma). In our study, all 48 dogs had a normal complete blood count, serum biochemical analysis, and urinalysis. Only one of the 48 dogs was found to have a serum AFP concentration > 225 ng/mL. Later evaluation of this dog confirmed hepatic involvement with lymphoma. AFP can be detected in the serum of dogs with naturally occurring tumors using the MEIA technique. A serum AFP concentration above that observed in normal dogs is not a common finding in dogs with naturally occurring neoplasia; however, we confirmed that a serum AFP concentration > 225 ng/mL, with or without evidence of a serum biochemical abnormality, may suggest primary and/or secondary hepatic involvement with a neoplastic disease and may warrant an adjustment in clinical stage and prognosis. A prospective diagnostic and therapeutic evaluation of dogs, with naturally occurring tumors having an elevated serum AFP concentration would determine the validity of this conclusion.     

Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer

The purpose of this study was to assess the toxicoses and antitumor activity of metronomic chlorambucil at a dosage of 4 mg m(-2) daily in dogs with naturally occurring cancer. Thirty-six dogs were enrolled in the study. The protocol was well tolerated with no grade 3 or 4 toxicoses noted. Complete remission was achieved, and lasted over 35 weeks in three dogs (mast cell tumour, soft tissue sarcoma and thyroid carcinoma). Partial remission was noted in 1 dog with histiocytic sarcoma (39 weeks duration) for an overall remission rate of 11% (4 of 36). Stable disease was noted in 17 dogs (47%) with various other cancers. The median progression-free interval was 61 days, and the median survival time was 153 days. Chlorambucil given in a metronomic protocol showed antitumor activity in dogs with a variety of naturally occurring cancers.     

Evaluation of pacing site in dogs with naturally occurring complete heart block

Objective

To compare left ventricular synchronization and systolic performance with transvenous pacing of the right ventricular apex (RVA), left ventricular free wall (LVF) or simultaneous pacing of the RVA and LVF (BiV).

Animals, materials and methods

Seven canine patients with complete heart block. Prospective study evaluating effect of pacing site. Twenty four hours following implantation of transvenous BiV pacing systems, electrocardiograms and echocardiograms were assessed during pacing from the: (1) Right Atrial Appendage/RVA (RAA/RVA), (2) RAA/LVF, and (3) RAA/BiV.

Results

QRS duration was significantly shorter with BiV pacing versus LVF pacing (p < 0.001), or RVA pacing (p < 0.001). Echocardiographic indices of systolic performance fractional shortening (FS), ejection fraction (EF), cardiac output (CO) were significantly higher with BiV pacing than with pacing from the RVA (P = 0.023, 0.006, and 0.002 respectively). Cardiac output, measured by the biplane Simpson's method, was higher with LVF versus RVA pacing (P = 0.036). There was no difference in FS or EF when comparing LVF to RVA pacing. Tissue Doppler measurements of synchronization and systolic performance did not show any difference between pacing mode, but a significantly increased number of segments were seen to contract following aortic valve closure during LVF pacing (P = 0.0268) and RVA pacing (P = 0.0197) as compared to BiV pacing.

Conclusions

Findings suggest that BiV pacing improves cardiac output and systolic performance versus RVA pacing. This improvement however, is not reflected in tissue Doppler indices of synchronization and systolic performance.     

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease

This multi-institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client-owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8–58.2) kg and in 31 cats was 3.9 (2.4–6.1) kg included in pharmacokinetic analyses. The dose, average steady-state serum concentrations (C_SS), and oral clearance in dogs were 14.2 (4.5–21.3) mg/kg/d, 26.8 (3.8–61.5) µg/mL, and 0.63 ml min⁻¹ kg⁻¹, respectively, and in cats were 18.6 (8.2–40.0) mg/kg/d, 32.1 (1.9–103.5) µg/mL, and 0.61 ml min⁻¹ kg⁻¹, respectively. Random inter-animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median C_SS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50–100 mg total daily dose in cats are recommended to achieve median C_SS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on C_SS (therapeutic drug monitoring) and treatment failure should be considered.     

Clinical pharmacokinetics of anti-angiogenic photodynamic therapy with benzoporphyrin derivative monoacid ring-A in dogs having naturally occurring neoplasms

The aim of this study was to examine the pharmacokinetics of clinically applied benzoporphyrin derivative monoacid ring-A (BPD-MA; Verteporfin), a second-generation photosensitizer, during a trial of photodynamic therapy (PDT) in nine dogs having naturally occurring neoplasms. After injecting BPD-MA at 0.5 mg/kg intravenously, its mean half-life (t1/2) was found to be 8.14 +/- 5.34 h, mean clearance (Cl) 35.13 +/- 9.62 ml/(h kg), the mean value of the volume of distribution (Vc) 0.08 +/- 0.01 l/kg and the mean steady state volume of distribution (Vss) 0.38 +/- 0.31 l/kg respectively. With the exception of a transitional increase in serum alkaline phosphatase activity, no other clinical abnormalities were observed. The t1/2 in dogs with naturally occurring tumours was longer than that in humans, but similar to that in rats. The values of Cl and Vss in dogs having naturally occurring neoplasms were lower than those in humans. It is suggested that the pharmacokinetics of BPD-MA in tumour-bearing dogs would be helpful in determining the protocol of a short drug-light interval PDT with BPD-MA that mainly targets the tumour vasculature.     

Evaluation of 1,2-O-dilauryl-rac-glycero glutaric acid-(6′-methylresorufin) ester (DGGR) and 1,2-diglyceride lipase assays in dogs with naturally occurring hypercortisolism

1,2-O-dilauryl-rac-glycero glutaric acid-(6′-methylresorufin) ester (DGGR) lipase activity has been proposed as a faster and less expensive test used in the diagnosis of acute pancreatitis (AP) compared to canine pancreatic lipase immunoreactivity (cPLI), which is considered the most sensitive and specific serum test available for dogs. Elevations in lipase activity have been observed in dogs with naturally occurring hypercortisolism (HC) and in those treated with exogenous steroids, which complicates the diagnosis of AP in dogs with HC. We compared lipase activity measured by DGGR and 1,2-diglyceride (1,2-DiG) assays in 22 dogs with HC, 22 with AP, and 22 healthy dogs. The dogs with HC had no clinical signs or ultrasonographic findings consistent with AP. DGGR lipase activity was elevated in 64% and 73% of the dogs with HC and AP, respectively, and in 18% of healthy dogs. 1,2-DiG lipase activity was high in 23% and 36% of the dogs with HC and AP, respectively, and in 5% of the healthy dogs. Both DGGR and 1,2-DiG lipase activities were significantly different between the healthy dogs and the other 2 groups, whereas no differences were detected between the dogs with HC and those with AP. Our results support a lack of specificity for both DGGR and 1,2-DiG lipase activity assays in aiding the diagnosis of AP in dogs with HC.     

Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range of asymptomatic MR (median serum IGF-1: 76.7 microg/L; 25-75 percentile, 59.8-104.9 microg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated congestive HF had similar serum IGF-1 concentrations (median, 100.8 g/L; 25-75 percentile, 74.9-156.5 microg/L) as 11 control dogs (79.6 microg/L; 25-75 percentile, 64.1-187.4 microg/L; P = .84). In study 3, the plasma IGF-1 concentration of 15 untreated CKCSs with severe MR was 16.4 +/- 24.2 microg/L lower (P = .02) at the examination when decompensated HF had developed (80.8 +/- 30.9 microg/L) than at a visit 1-12 months earlier (97.2 +/- 39.8 microg/L), possibly in part due to an altered state of nutrition. The studies document that circulating IGF-1 concentrations are not altered before development of congestive HF in dogs with naturally occurring MR, but decrease by approximately 20% with the development of untreated HE In treated HF, circulating IGF-1 concentrations apparently return to within the reference range.     

Clinical evaluation of gemcitabine in dogs with spontaneously occurring malignancies

We conducted a clinical evaluation of gemcitabine in 19 dogs with spontaneously occurring malignancies. The principal objectives of this study were to characterize toxicity and seek preliminary evidence of antitumor activity of gemcitabine administered every 2 weeks (biweekly) as a 30-minute IV infusion. A total of 64 doses, ranging from 300 mg/m2 to 675 mg/m2, were administered during the initial 8-week evaluation period, and an additional 131 doses were administered during the extended evaluation period. The total cumulative dose for the 10 dogs receiving gemcitabine in the extended evaluation period ranged from 1,500 mg/m2 to 24,300 mg/m2. Clinical evidence of toxicity was minimal. Cumulative myelosuppression was not apparent. Unexplained retinal hemorrhages occurred in 1 dog. No complete or partial remissions were observed during the initial evaluation period; however, objective responses were observed in 2 dogs during the extended evaluation period. Gemcitabine is a promising new chemotherapeutic agent that can be used safely in dogs with cancer. Biweekly administration of doses of 675 mg/m2 IV results in minimal and acceptable toxicity.     

Phase I evaluation of low-dose suramin as chemosensitizer of doxorubicin in dogs with naturally occurring cancers

BACKGROUND: Low and nontoxic concentrations (10-50 microM) of suramin, which is a nonspecific inhibitor of multiple growth factors, including fibroblast growth factors, enhances the activities of cytotoxic chemotherapeutic agents, such as doxorubicin and paclitaxel, both in vitro and in vivo. Suramin has not been evaluated as a chemosensitizing agent in dogs with cancer. HYPOTHESIS: Nontoxic suramin can be used safely as a chemosensitizer in dogs. ANIMALS: Sixteen dogs of various breeds with measurable tumors were treated; 1 dog that had undergone amputation for osteosarcoma received adjuvant therapy. METHODS: The dogs received 53 courses of treatment with suramin in combination with doxorubicin. The suramin dosage was 6.75 mg/kg IV 3 h before standard doxorubicin administration every 2 weeks. The pharmacokinetics and clinical efficacy were determined. RESULTS: The pharmacokinetics of low-dose suramin followed a 2-compartment model with half-lives of 2 h and 6 days. The distribution volume was a 0.34 +/- 0.12 L/kg, and clearance was 1.86 +/- 0.76 mL/kg/h. During the time interval that doxorubicin was present at therapeutically active concentrations (ie, from the start of infusion to 24 hours), the plasma concentrations were maintained within 20% of the target range (8-60 microM) in 72% of the treatments. The toxicity of the suramin/doxorubicin combination was mild and comparable to the toxicity expected for doxorubicin monotherapy. Objective partial responses were observed in 2 out of 16 evaluable dogs (13%). All 5 dogs that previously received doxorubicin showed improved responses to the suramin/doxorubicin combination. CONCLUSIONS AND CLINICAL IMPORTANCE: A fixed, low-dose suramin regimen yields the desired target plasma concentrations in most dogs, and appears to enhance the activity of doxorubicin without enhancing toxicity.     

Use of an ultrasonically activated scalpel for splenectomy in 10 dogs with naturally occurring splenic disease

OBJECTIVE:To evaluate the safety and efficacy of an ultrasonically activated scalpel for performing splenectomy, with minimal ligation, in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs (10) with naturally occurring splenic disease. METHODS: Between October 2003 and February 2004, splenectomy was performed using an ultrasonically activated scalpel and a double seal method, in 10 dogs with naturally occurring splenic disease. Time for splenectomy and number of ligatures required were recorded. Intraoperative hemostasis, device ease of use, postoperative hemorrhage, and short-term survival were evaluated. RESULTS: Mean operative time for splenectomy, exclusive of celiotomy and closure, was 18 minutes (range, 8-25 minutes). The mean number of ligatures needed to perform splenectomy was 1 (range, 0-2 ligatures). One dog hemorrhaged from the splenic vein after ultrasonic scalpel transection of a vessel >5-mm diameter and required a ligature. The ultrasonic scalpel was easy to use, with a minimal learning curve. None of the dogs had postoperative abdominal hemorrhage; 9 dogs were discharged and 1 dog was euthanatized because of septicemia. CONCLUSION: Ultrasonic activated scalpel may be used to achieve efficient and safe hemostasis of the splenic vascular pedicle in dogs with minimal need for vascular ligation. CLINICAL RELEVANCE: Ultrasonic scalpels can be used to perform splenectomy in dogs with naturally occurring splenic disease.     

The effect of dietary corn oil and fish oil supplementation in dogs with naturally occurring gingivitis

The aim of this randomized, double‐blinded, placebo‐controlled study was to evaluate if downregulation of the inflammatory response due to ingestion of high levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can slow down gingivitis development, and thus delay the progression of periodontal disease (PD) in dogs. To this aim, 44 client‐owned adult dogs (>1 and <8 years old) with naturally occurring PD (stages 1 and 2) were submitted to a plaque, gingivitis and calculus scoring followed by a dental cleaning procedure and collection of blood samples. The animals were then fed a canine adult maintenance diet, supplemented with either corn oil (0.00 g EPA and 0.00 g DHA) or fish oil (1.53 g EPA and 0.86 g DHA, both per 1,000 kcal ME) over the following 5 months. At the end of this period, the PD scoring and the blood sampling were repeated. The animals consuming fish oil had higher plasma levels of the longer chain (C ≥ 20) omega 3 fatty acids (p < 0.01) and similar plasma levels of alpha‐linolenic acid (p = 0.53), omega 6 fatty acids (p > 0.63) and C reactive protein (p = 0.28) then the ones consuming corn oil. There were no differences between fish oil and corn oil diet supplementation on plaque (18.2 vs. 17.8, p = 0.78), calculus (10.1 vs. 11.5, p = 0.18) or gingivitis (19.3 vs. 19.0, p = 0.77) indexes. The authors conclude that supplementation with EPA + DHA does not slow down progression of PD in dogs.     

Clinical and microbiological characterization of subclinical bacteriuria and sporadic bacterial cystitis in dogs with spontaneous hypercortisolism

Study’s aims were to characterize subclinical bacteriuria (SB) and sporadic bacterial cystitis (SBC) in dogs with spontaneous hypercortisolism (HC). Prospective cross-sectional design divided patients as newly diagnosed (n = 27), poorly controlled (n = 21), well controlled (n = 34), and controls (n = 19). Urine culture positive results were identified by MALDI-TOF and submitted to antibiogram. Escherichia coli was the most common microorganism (36%). The majority of positive cultures in HC were SB (12.2%). All 4.1% SBC cases were in well controlled HC cases. Bacteriuria correlated with low urine specific gravity and low lymphocyte count. HC degree of control correlated with leukocyturia. SB/SBC cases were treated based in antimicrobial susceptibility leading to microbiological cure in 75% of HC cases. Persistent infections occurred only in SB cases, all by E. coli which became more resistant. SB/SBC prevalence in canine HC is actually lower. Further evidence for current ISCAID guideline contraindication for SB treatment due to HC were provided.