Evaluating the use of cytosine arabinoside for treatment for recurrent canine steroid-responsive meningitis-arteritis

BackgroundRelapses in steroid-responsive meningitis-arteritis (SRMA) are frequently observed but specific treatment protocols to address this problem are sparsely reported. Standard treatment includes prolonged administration of glucocorticoids as monotherapy or in combination with immunosuppressive drugs. The aim of this study was to assess the safety and efficacy of cytosine arabinoside (CA) in combination with glucocorticoids for treatment of SRMA relapses in 12 dogs on a retrospective basis.MethodsDogs with recurrent episodes of SRMA and treated with a combination of CA and prednisolone were included. Information about clinical course, treatment response and adverse events was collected from medical records. Ethical approval was not required for this study.ResultsTen dogs (10/12) responded well to the treatment with clinical signs being completely controlled. One dog is in clinical remission, but still under treatment. One dog (8%) showed further relapse. Mean treatment period was 51 weeks. Adverse events of variable severity (grade 1–4/5) were documented in all dogs during treatment according to the veterinary cooperative oncology group grading. Three dogs developed severe adverse events. Laboratory findings showed marked changes up to grade 4. Diarrhoea and anaemia were the most often observed adverse events (6), followed by dermatitis (4), alopecia (3) and pneumonia (3). Including blood chemistry changes (13), 50 adverse events were found in total.ConclusionTreatment with CA and glucocorticoids resulted in clinical remission in 10/12 dogs, but a high incidence of adverse events occurred requiring additional measures. All adverse events could be managed successfully in all cases.</jats:sec

Predicting Major Adverse Events in Patients With Acute Myocardial Infarction

Early and accurate detection of short-term major adverse cardiac events (MACE) in patients with suspected acute myocardial infarction (AMI) is an unmet clinical need.; The goal of this study was to test the hypothesis that adding clinical judgment and electrocardiogram findings to the European Society of Cardiology (ESC) high-sensitivity cardiac troponin (hs-cTn) measurement at presentation and after 1 h (ESC hs-cTn 0/1 h algorithm) would further improve its performance to predict MACE.; Patients presenting to an emergency department with suspected AMI were enrolled in a prospective, multicenter diagnostic study. The primary endpoint was MACE, including all-cause death, cardiac arrest, AMI, cardiogenic shock, sustained ventricular arrhythmia, and high-grade atrioventricular block within 30 days including index events. The secondary endpoint was MACE + unstable angina (UA) receiving early (≤24 h) revascularization.; Among 3,123 patients, the ESC hs-cTnT 0/1 h algorithm triaged significantly more patients toward rule-out compared with the extended algorithm (60%; 95% CI: 59% to 62% vs. 45%; 95% CI: 43% to 46%; p < 0.001), while maintaining similar 30-day MACE rates (0.6%; 95% CI: 0.3% to 1.1% vs. 0.4%; 95% CI: 0.1% to 0.9%; p = 0.429), resulting in a similar negative predictive value (99.4%; 95% CI: 98.9% to 99.6% vs. 99.6%; 95% CI: 99.2% to 99.8%; p = 0.097). The ESC hs-cTnT 0/1 h algorithm ruled-in fewer patients (16%; 95% CI: 14.9% to 17.5% vs. 26%; 95% CI: 24.2% to 27.2%; p < 0.001) compared with the extended algorithm, albeit with a higher positive predictive value (76.6%; 95% CI: 72.8% to 80.1% vs. 59%; 95% CI: 55.5% to 62.3%; p < 0.001). For 30-day MACE + UA, the ESC hs-cTnT 0/1 h algorithm had a higher positive predictive value for rule-in, whereas the extended algorithm had a higher negative predictive value for the rule-out. Similar findings emerged when using hs-cTnI.; The ESC hs-cTn 0/1 h algorithm better balanced efficacy and safety in the prediction of MACE, whereas the extended algorithm is the preferred option for the rule-out of 30-day MACE + UA. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587)

Neue Hoffnung bei maligner Histiozytose

Das histiozytäre Sarkom ist eine bösartige Krebserkrankung, die bei einigen Rassen gehäuft, insgesamt aber bei Hunden eher selten vorkommt. Da der Tumor höchst verschiedene Gesichter zeigt, ist es für den behandelnden Tierarzt nicht immer einfach, sofort eine klare Diagnose zu stellen. Eine von der Albert-Heim-Stiftung finanziell unterstützte und in der Vetsuisse Fakultät Zürich realisierte Studie zu diesem Thema liefert interessante Resultate

Safety, tolerability and pharmacokinetic properties of the novel triazene TriN 2755 in tumor bearing dogs

TriN 2755 is an alkylating antineoplastic agent for intravenous (IV) use, carrying the triazene group as the cytotoxic principal. Using a standard 3 + 3 design, a phase I study was performed in tumour bearing dogs to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and pharmacokinetic (PK) profile of TriN 2755. Thirty dogs were included in the study. TriN 2755 was administered over 20 min on two consecutive weeks per month for a total of three cycles. The starting dose was 25 mg kg-1 and the MTD was 74.6 mg kg-1 . Three dogs experienced DLT, which was characterized by gastrointestinal adverse events. The PKs of TriN 2755 and its main metabolites in plasma and sputum are described in a two-compartment model. The response rate for 19 of 30 dogs was 47.3% (six partial remission, three stable disease) and the median progression-free interval (PFI) for the responders was 47 days (range: 21-450 days)

Does a pleiotropic gene explain deafness and blue irises in white cats?

The prevalence of deafness is high in cat populations in which the dominant white gene is segregating. The objective of this study was to investigate whether there is a gene that is responsible for deafness as well as for blue eyes and to establish a plausible mode of inheritance. For this purpose, data from an experimental colony with deaf cats were analyzed. The hearing status was determined by acoustically evoked brain stem responses (BAER). Complex segregation analyses were conducted to find out the most probable mode of inheritance using maximum likelihood procedures. The prevalence of deafness and partial hearing in the experimental colony was 67% and 29%, respectively. The results of the bivariate segregation analysis support the hypothesis of a pleiotropic major gene segregating for deafness and blue iris colour. The high heritability coefficients for both traits, 0.55 and 0.75 respectively, indicate that beside the major gene there is an important influence of polygenic effects

Use of Epothilone B (Patupilone) in Refractory Lymphoma and advanced solid tumors in dogs

Background: The epothilones are microtubule-stabilizing agents with promising antitumor effect in refractory and metastatic tumors in humans. The toxicity profile is considered more favorable than in taxanes. The safety of epothilone B (patupilone) has not been evaluated in tumor-bearing dogs. Objectives: To evaluate the inhibition of proliferation in canine tumor cells after patupilone treatment. To assess toxicity profile and maximally tolerated dose of patupilone in dogs with refractory tumors. Animals: Twenty client-owned dogs with various malignancies. Methods: The inhibition of proliferation was assessed with a proliferation assay in vitro in canine hemangiosarcoma and lymphoma cell lines. In the prospective clinical study, dogs received patupilone intravenously once a week for two treatments (= one treatment cycle). Dose was escalated with three dogs per cohort and 20% increments. Adverse effects were graded according to the VCOG-CTCAE v1.0. Results: Both canine cell lines were sensitive to patupilone with approximately 50% decrease of proliferative activity at 0.2-1 nM. In vivo, dose-limiting adverse effects occurred at 3.3 mg/m2; main adverse effects were diarrhea, anorexia, vomiting, and nausea. Neither neutropenia nor peripheral neuropathy was observed. Maximally tolerated dose for two patupilone administrations once weekly IV is 2.76 mg/m2. 3/11 dogs receiving more than one treatment cycle showed partial remission in the short period of observation. Conclusions and Clinical Importance: Canine tumor cells show inhibition of proliferation to patupilone in vitro. Clinically, a dose of 2.76 mg/m2 IV is well tolerated in dogs with spontaneously occurring tumors

Isolation and genotyping of Toxoplasma gondii causing fatal systemic toxoplasmosis in an immunocompetent 10-year-old cat

A 10-year-old male, neutered domestic shorthair cat was presented with fever, anorexia, vomiting, and diarrhea. Serologic testing for Feline immunodeficiency virus and Feline leukemia virus were negative. Fine-needle aspirates of mesenteric lymph nodes revealed the presence of banana-shaped apicomplexan parasites. The cat died after 4 days of hospitalization. Postmortem polymerase chain reaction (PCR) analysis confirmed the presence of Toxoplasma gondii in all examined organs. Parasites were ex vivo isolated in outbred mice and subsequently transferred into cell culture. Genotyping, using genetic markers for SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico for PCR-restriction fragment length polymorphism, revealed infection with type II T. gondii displaying type II alleles at all loci except Apico, which exhibited a type I allele. This is the most frequently identified genotype among cats acting as definitive hosts in central Europe, but to the authors' knowledge, it has never been associated with systemic toxoplasmosis in an adult, immunocompetent cat