Veterinary Clinical Sciences - Research Publications
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ItemA retrospective multi-center study of treatment, outcome, and prognostic factors in 34 dogs with disseminated aspergillosis in Australia(WILEY, 2022-03)BACKGROUND: Disseminated aspergillosis (DA) in dogs has a guarded prognosis and there is a lack of a gold standard treatment protocol. OBJECTIVE: To retrospectively assess survival times and factors influencing survival times. ANIMALS: Dogs diagnosed with DA from January 2007 to June 2017. METHODS: Disseminated 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. RESULTS: Thirty-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 ( χ 2 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 IMPORTANCE: Serum 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).
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ItemTreatment response and long term follow up in nineteen dogs diagnosed with chronic enteropathy in Australia(WILEY, 2019-09)Chronic enteropathy (CE) in dogs is common worldwide, but little data is available from Australia. The aim of this study was to describe treatment response and long-term outcome in a cohort of dogs with CE. Dogs were prospectively enrolled at Murdoch University and the University of Melbourne. After diagnostic investigation to rule out diseases other than CE, dogs underwent sequential therapeutic trials until achieving a clinical response (diet then antibiotics, and finally immunosuppressants). Success was defined as 75% reduction of clinical severity for a minimum of five weeks. A total of 21 dogs were enrolled, and 19 completed the study. One dog was euthanised for lack of response to treatment and one excluded for lack of owner compliance. Most dogs responded to diet (n = 10), followed by antibiotics (n = 7) and immunosuppressants (n = 2). Long-term remission (median 21.1 months, [3.0-44.7]) was achieved in eight out of ten dietary responders without additional treatment. In contrast, only two dogs with antibiotic response remained in long-term remission, of which one needed on-going antibiotic treatment. Longer term remission was achieved in the two dogs treated with immunosuppressants with on-going low dose therapy. This study concludes that most dogs referred for CE in Australia respond to dietary treatment (even after previous dietary interventions), and remission is long-term compared to dogs treated with an antibiotic. Furthermore, the need for long-term antibiotics in some dogs to maintain response may lead to antibiotic resistance. This study supports adequate dietary trials for CE in dogs, and a need for alternative second-line treatments.
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ItemA retrospective multi-centre study on treatment and outcome in disseminated aspergillosis in 41 dogs(American College of Veterinary Internal Medicine, 2020)
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ItemChronic Enteropathy In Canines: Prevalence, Impact And Management Strategies(Dove Press, 2019-12-06)In this article, the studies about the prevalence of chronic enteropathy are reviewed as well as the information regarding short- and long-term prognosis for dogs treated with the three most common therapies; these include dietary modification, antibiotics, and immunosuppressants. Although the data available are limited, most studies support a good to excellent long-term response in dogs that have a successful food trial, whereas the response is poor with antibiotics or on-going treatment is required to retain remission. There is a risk of antimicrobial resistance developing with inappropriate use of antimicrobials such as in these situations. The published information highlights the need for alternative strategies to antibiotic treatment to manipulate the GI microbiome, and in the final part of this article studies on the use of probiotic for the treatment of chronic enteropathy are reviewed.
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ItemChanges in duodenal CD163-positive cells in dogs with chronic enteropathy after successful treatment(SAGE PUBLICATIONS LTD, 2018-10)Chronic enteropathy (CE) in dogs is characterized retrospectively per treatment response as food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), and immunosuppressant-responsive enteropathy (IRE) - the latter most resembling inflammatory bowel disease in people. The aim of this study was to characterize duodenal macrophages (Mϕ) in CE using immunohistochemistry; with calprotectin (CAL) as a marker of early differentiated Mϕ and CD163 expression as a marker for resident Mϕ in the duodenum before and after treatment. Prior to treatment, dogs with FRE and IRE had a lower CD163+/CAL+ ratio than control dogs (CTRL) in crypts; this increased significantly and normalized compared with CTRL after treatment. Conversely, the CD163+/CAL+ ratio in dogs with ARE was comparable to that in healthy dogs before and after treatment. In summary, these results suggest that Mϕ play a role in the pathogenesis of CE in FRE and IRE, with a decrease in resident Mϕ and an increase in early differentiated Mϕ, but not in ARE dogs. Mϕ normalize after successful treatment.
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ItemEffect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12-myristate 13-acetate(John Wiley & Sons, 2019-05)A pharmacodynamic assay has been previously developed to monitor ciclosporin treatment in dogs by assessing inhibition of cytokine transcription after whole blood stimulation with 12-myristate 13-1 acetate and ionomycin (PMA/I). In this study, whole blood stimulation with either PMA/I or lipopolysaccharide (LPS) was used to assess the effect of multiple drugs (azathioprine, ciclosporin, mycophenolate, leflunomide and prednisone) after a 7-day treatment course on production of cytokines measured with a multiplex assay in healthy dogs (n = 4 for each treatment). Interleukin-10 (IL-10), interferon gamma (IFN?) and tumour necrosis factor alpha (TNFa) were significantly activated by PMA/I stimulation and IL-6, IL-10 and TNFa by LPS stimulation, in the absence of immunosuppressive drugs. After ciclosporin treatment, IL-10, IFN? and TNFa production was significantly reduced after stimulation with PMA/I compared to pre-treatment. After prednisone treatment, TNFa production was significantly reduced after stimulation with PMA/I or LPS compared to pre-treatment. No significant change was observed after treatment with azathioprine, leflunomide or mycophenolate. This methodology may be useful to monitor dogs not only treated with ciclosporin, but also with prednisone or a combination of both. Further studies are needed to assess the use of this assay in a clinical setting.