A randomized, blinded, controlled clinical trial comparing the efficacy of aminosidine (paromomycin)-allopurinol combination with the efficacy of meglumine antimoniate-allopurinol combination for the treatment of canine leishmaniosis due to Leishmania infantum.

The aim of this 6-month, randomized, blinded, controlled clinical trial was to compare the efficacy and safety of aminosidine-allopurinol combination with that of meglumine antimoniate-allopurinol combination for the treatment of leishmaniosis in dogs without stage III or IV chronic kidney disease. Forty client-owned dogs were randomly assigned to group A [n = 20; aminosidine (15 mg/kg, subcutaneously, once daily, for 28 days) and allopurinol (10 mg/kg, per os, twice daily, for 6 months)] or group B [(n = 20; meglumine antimoniate (100 mg/kg SC, once daily, for 28 days) and allopurinol (10 mg/kg, per os, twice daily, for 6 months)]. Clinical and clinicopathological evaluations, parasitic load measurement (lymph node and bone marrow microscopy, bone marrow real-time PCR), specific serology and leishmanin skin test (LST) were performed at baseline (time 1) and after 14 (time 2), 28 (time 3), 60 (time 4) and 180 (time 5) days. Both treatments were safe and resulted in significant clinical and clinicopathological improvement, reduction of parasitic load and of indirect immunofluorescence antibody test (IFAT) titer and induction of positive LST. There was no significant difference between groups with regards to the primary outcome measures of the trial that included the proportion of dogs that presented severe treatment-related side effects, were cured and were parasitologically negative at time 5. However, some (proportion of dogs that presented no clinical signs, no hyperglobulinemia and negative serology at time 5) secondary outcome measures showed significant differences in favor of the meglumine antimoniate-allopurinol treatment arm. Treatment-related death occurred in one dog in each group, while injection site reactions appeared at a similar frequency in both groups. Due to the differences in some secondary outcome measures in association with the low power of this trial, it cannot be definitively concluded that the two treatments are equally effective. Therefore, the aminisodine-allopurinol combination cannot be proposed as a first-line treatment of CanL but rather as a second-line treatment that may be particularly useful to avoid repeated administration of meglumine antimoniate and in countries where the latter is not available or registered.

Evaluation of nephrotoxicity and ototoxicity of aminosidine (paromomycin)-allopurinol combination in dogs with leishmaniosis due to Leishmania infantum: A randomized, blinded, controlled study.

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.

Impact of fine- or large-needle aspiration on canine testes: clinical, in vivo ultrasonographic and seminological assessment.

The safety and consequences of fine- (FNA) and large-needle aspiration (LNA) to the testicular parenchyma and its normal function have not been thoroughly established. This study was performed to accurately assess, by serial clinical, in vivo ultrasonographic and seminological examinations, the type and extent of the effect of FNA or LNA on canine testes. Eighteen sexually mature, 1-2 years old, healthy laboratory Beagles were used. One of their testes was aspirated using a 23-G butterfly needle (FN) and the other using a 19-G butterfly needle (LN). Two dogs at a time were orchiectomized 10, 60 min, 2, 14, 29, 63, 76, 90 or 180 days post-aspiration. Five and 2 days and 1 h before aspiration (in all dogs), immediately post-aspiration, and 1, 2, 4, 7, 9, 14, 19, 29, 35, 43, 49, 56, 63, 70, 76, 90, 111, 132 and 180 days post-aspiration (in the remaining intact dogs), evaluation of scrotal surface temperature over each testis, evaluation of scrotum-testis volume by electronic sliding callipers, ultrasonographic evaluation of testicular volume and texture and clinical and semen examination were performed. Following FNA and LNA, the clinical and ultrasonographic appearance of the testis were normal. Sperm production nearly always remained unchanged, with the exception of a slight decrease in spermatozoal motility 2-14 days post-aspiration. However, even then, with the exception of six samples, spermatozoal motility was above normal values. Within the parameters of this experiment, testicular FNA and LNA have no ill effect on sperm production or clinical and ultrasonographic appearance of the canine testis, and therefore, both FNA and LNA should be considered safe.

Impact of fine or large needle aspiration on the dog's testis: in vitro ultrasonographic, bacteriological, gross anatomy and histological assessment.

Despite its extensive use for evaluation of spermatogenesis and assisted reproduction, the safety and consequences of fine (FNA) and large needle aspiration (LNA) to the testicular parenchyma and its normal function have not been established. This study was performed in order to accurately assess, by serial in vitro ultrasonographic, bacteriologic, gross anatomic and histological examinations, the type and extent of the effect of FNA or LNA on the dog's testis. Twenty three sexually mature, 1 to 2 years old, healthy laboratory Beagles were randomly assigned to 2 groups: (1) 5 dogs without testicular aspiration (control group) and (2) 18 dogs in which one of their testes was aspirated using a 23 G butterfly needle and the other using a 19 G butterfly needle (experimental group). Two dogs at a time were castrated 10 minutes, 60 minutes, 2, 14, 29, 63, 76, 90 or 180 days post-aspiration. The control group was also castrated 2, 29, 63, 90 or 180 days after the beginning of the experiment. Following castration, in vitro ultrasonographic, gross anatomic, cytological examinations of epididymal sperm, bacteriologic and histological examinations of the testes were performed. Following testicular FNA and LNA bacteriologic, gross anatomic, histologic, epididymal sperm findings and the in vitro ultrasonographic appearance of the testis were normal, except of intratesticular haemorrhage, detected the first days post-aspiration, and degeneration of less than 1.5% of the seminiferous tubules. Within the parameters of this experiment, testicular FNA and LNA have no ill effect on the canine testis and therefore, both FNA and LNA should be considered safe.

A retrospective study of 61 cases of spontaneous canine epistaxis (1998 to 2001).

OBJECTIVES: To determine the prevalence and identify possible clinicopathologic indicators of the diseases associated with canine epistaxis. METHODS: The medical records of 61 dogs with epistaxis were reviewed. RESULTS: Systemic diseases, diagnosed in fifty-six dogs, included canine leishmaniasis in twenty-three dogs, canine monocytic ehrlichiosis in twenty-two, concurrent canine leishmaniasis and canine monocytic ehrlichiosis in six, rodenticide toxicity in two and primary immune-mediated thrombocytopenia, suspected oestrogen toxicity and systemic arterial hypertension in one dog each. Intranasal diseases were documented in the remaining five dogs, including transmissible venereal tumour in three dogs, and nasal adenocarcinoma and nasal aspergillosis in one dog each. Mucosal pallor and a generalised bleeding tendency were significantly more common among dogs with canine monocytic ehrlichiosis compared with those with canine leishmaniasis, whereas the opposite was true for peripheral lymphadenomegaly. Also, dogs with canine monocytic ehrlichiosis presented with pancytopenia more frequently compared with those with canine leishmaniasis; in the latter dogs, the median values of haematocrit, leucocyte and platelet counts and serum total protein concentrations were higher. CLINICAL SIGNIFICANCE: Canine leishmaniasis and canine monocytic ehrlichiosis are the leading causes of canine epistaxis in Greece. Mucosal pallor, bleeding tendency and pancytopenia are more likely to be indicative of canine monocytic ehrlichiosis, as opposed to peripheral lymphadenomegaly and hyperproteinaemia in canine leishmaniasis.

Evaluation of cytology in the diagnosis of acute canine monocytic ehrlichiosis (Ehrlichia canis): a comparison between five methods.

The purpose of this study was the comparison of the diagnostic sensitivity between buffy coat (BC), peripheral blood (PB), lymph node (LN), bone marrow (BM) and short-term culture (P-D) cytology that has been based on the detection of Ehrlichia canis morulae, in the acute phase of canine monocytic ehrlichiosis (CME). Their cellular localization, total numbers and microscopic differentials were also investigated. The highest sensitivities were achieved after evaluating 1000 oil immersion fields (OIFs) in BC (66%) and an equal number in LN (60.9%) smears, separately or together (74%). The morulae were more often detected into lymphocytes than monocytes. The highest total number of morulae (n=143) were found in P-D smears. Finally, to avoid false positive diagnoses, platelets, lymphocytic azurophilic granules, lymphoglandular bodies and phagocytosed nuclear material should not be confused with the morulae.