Canine T‐Zone Lymphoma: Unique Immunophenotypic Features,Outcome, and Population Characteristics

Background

Canine T‐cell lymphoma (TCL) is clinically and histologically heterogeneous with some forms, such as T‐zone lymphoma (TZL), having an indolent course. Immunophenotyping is an important tool in the classification of TCL in people, and can be equally useful in dogs.

Hypothesis/Objectives

We hypothesized that loss of expression of the CD45 antigen is a specific diagnostic feature of TZL.

Animals

Twenty dogs with concurrent histology and immunophenotyping by flow cytometry were studied in depth. An additional 494 dogs diagnosed by immunophenotyping were used to characterize the population of dogs with this disease.

Methods

Lymph node biopsies from 35 dogs with TCL were classified by 2 pathologists using WHO criteria. Twenty lymph nodes were from dogs with CD45− TCL and 15 were from CD45+ TCL. The pathologists were blinded to the flow cytometry findings. Outcome information was sought for the 20 dogs with CD45− lymphoma, and population characteristics of the additional 494 dogs were described.

Results

All 20 CD45− cases were classified as TZL. The 15 CD45+ cases were classified as aggressive TCL and are described in an accompanying paper. TZL cases had a median survival of 637 days. Examination of 494 additional dogs diagnosed with TZL by immunophenotyping demonstrated that 40% of cases are in Golden Retrievers, are diagnosed at a median age of 10 years, and the majority have lymphadenopathy and lymphocytosis.

Conclusions

TZL has unique immunophenotypic features that can be used for diagnosis.     

Good agreement of conventional and gel-based direct agglutination test in immune-mediated haemolytic anaemia

Background

The aim of this study was to compare a gel-based test with the traditional direct agglutination test (DAT) for the diagnosis of immune-mediated haemolytic anaemia (IMHA).

Methods

Canine (n = 247) and feline (n = 74) blood samples were submitted for DAT testing to two laboratories. A subset of canine samples was categorized as having idiopathic IMHA, secondary IMHA, or no IMHA.

Results

The kappa values for agreement between the tests were in one laboratory 0.86 for canine and 0.58 for feline samples, and in the other 0.48 for canine samples. The lower agreement in the second laboratory was caused by a high number of positive canine DATs for which the gel test was negative. This group included significantly more dogs with secondary IMHA.

Conclusions

The gel test might be used as a screening test for idiopathic IMHA and is less often positive in secondary IMHA than the DAT.     

Experimental infection of dogs with a feline endogenous retrovirus RD-114

Background

The feline endogenous retrovirus RD114 is contained in the genome of cats. The virus may contaminate live canine vaccines based on cultured feline cells. The in vivo infectivity, acute and subacute pathogenicity, and viral proliferation of the RD114 virus were evaluated by experimental infection of dogs.

Methods

Nine specific pathogen free dogs were divided into three groups, with each group consisting of one female and two male dogs. Dogs were subcutaneously inoculated in the neck with either 1 ml RD114 stock virus (group A), inactivated RD114 virus suspension (group B), or cell culture medium (group C) as a negative control. To assess blood cell counts and biochemical properties, blood samples from each group were collected 5 days before inoculation, just prior to inoculation, and 1, 3, 7 and 10 days post-inoculation.

Result

During the experimental period of 51 days, none of the dogs inoculated with RD114 virus showed any clinical signs, significant increases in rectal temperature or abnormal blood biochemical characteristics including C-reactive protein when compared with the negative controls. We were not able to re-isolate the RD114 virus from buffy coat cells of group A dogs. Additionally, we could not detect RD114 provirus in the genomic DNA isolated from peripheral blood leukocytes, lymph node, spleen and sternal bone marrow cells.

Conclusions

Signs of RD114 virus proliferation were not found after subcutaneous infection of dogs. Although the potential risk caused by infection with RD114 virus in dogs could not be assessed in this study, we suspect that RD114 virus has little or no virulence in dogs.     

Modular hybrid total hip arthroplasty. Experimental study in dogs

Background

This prospective experimental study evaluated the surgical procedure and results of modular hybrid total hip arthroplasty in dogs.

Methods

Ten skeletally mature healthy mongrel dogs with weights varying between 19 and 27 kg were used. Cemented modular femoral stems and uncemented porous-coated acetabular cups were employed. Clinical and radiographic evaluations were performed before surgery and at 30, 60, 90, 120, 180 and 360 days post-operation.

Results

Excellent weight bearing was noticed in the operated limb in seven dogs. Dislocation followed by loosening of the prosthesis was noticed in two dogs, which were therefore properly treated with a femoral head osteotomy. Femoral fracture occurred in one dog, which was promptly treated with full implant removal and femoral osteosynthesis.

Conclusions

The canine modular hybrid total hip arthroplasty provided excellent functionality of the operated limb.     

The use of the rapid osmotic fragility test as an additional test to diagnose canine immune-mediated haemolytic anaemia

Background

Diagnosing canine immune-mediated haemolytic anaemia (IMHA) is often challenging because all currently available tests have their limitations. Dogs with IMHA often have an increased erythrocyte osmotic fragility (OF), a characteristic that is sometimes used in the diagnosis of IMHA. Since the classic osmotic fragility test (COFT) is time-consuming and requires specialized equipment, an easy and less labour-intensive rapid osmotic fragility test (ROFT) has been used in some countries, but its diagnostic value has not yet been investigated.This study aimed to evaluate erythrocyte osmotic fragility in dogs with and without IMHA, to compare results of the classic (COFT) and rapid (ROFT) test and to assess the value of the ROFT as diagnostic test for canine IMHA.Nineteen dogs with IMHA (group 1a), 21 anaemic dogs without IMHA (group 1b), 8 dogs with microcytosis (group 2), 13 hyperlipemic dogs (group 3), 10 dogs with lymphoma (group 4), 8 dogs with an infection (group 5) and 13 healthy dogs (group 6) were included.In all dogs, blood smear examination, in-saline auto-agglutination test, Coombs’ test, COFT and ROFT were performed. In the COFT, OF5, OF50 and OF90 were defined as the NaCl concentrations at which respectively 5, 50 and 90% of erythrocytes were haemolysed.

Results

Compared with healthy dogs, OF5 and OF50 were significantly higher in group 1a (P < 0.001) and OF5 was significantly higher in group 3 (P = 0.0266). The ROFT was positive in 17 dogs with IMHA, 10 hyperlipemic dogs, one anaemic dog without IMHA and one healthy dog.

Conclusions

Osmotic fragility was increased in the majority of dogs with IMHA and in dogs with hyperlipidemia, but not in dogs with microcytosis, lymphoma or an infection. Although more detailed information was obtained about the osmotic fragility by using the COFT, the COFT and ROFT gave similar results. The ROFT does not require specialized equipment, is rapid and easy to perform and can be used easily in daily practice. Although, the ROFT cannot replace other diagnostic tests, it may be a valuable additional tool to diagnose canine IMHA.     

Haemostatic alterations in a group of canine cancer patients are associated with cancer type and disease progression

Background

Haemostatic alterations are commonly detected in human and canine cancer patients. Previous studies have described haemostatic dysfunction in canine patients with haemangiosarcomas and carcinomas, and haemostasis has been assessed in dogs with various malignant and benign neoplasias. Few studies have addressed the effect of cancer type and progression of disease on the presence of haemostatic alterations in canine patients. The objective of the present study was to evaluate haemostatic variables of coagulation and fibrinolysis in a group of canine cancer patients, and to compare haemostatic changes to the cancer type and progression of disease.

Methods

The study population consisted of 71 dogs with malignant neoplasia presented to the University Hospital for Companion Animals, Faculty of Life Sciences, University of Copenhagen, Denmark. The study was designed as a prospective observational study evaluating the haemostatic function in canine cancer patients stratified according to type of cancer disease and disease progression. The coagulation response was evaluated by thromboelastrography (TEG), platelet count, activated partial thromboplastin time (aPTT), prothombin time (PT), fibrinogen and antithrombin (AT); and fibrinolysis by d-dimer and plasminogen.

Results

Hypercoagulability was the most common haemostatic dysfunction found. Non mammary carcinomas had increased clot strength (TEG G), aPTT and fibrinogen compared to the other groups. When stratifying the patients according to disease progression dogs with distant metastatic disease exhibited significantly increased fibrinogen, and d-dimer compared to dogs with local invasive and local non-invasive cancers.

Conclusion

Hypercoagulability was confirmed as the most common haemostatic abnormality in canine cancer patients and haemostatic dysfunction in canine cancer patients was found related to the cancer type and progression of disease. Increase in TEG G, aPTT and fibrinogen were observed in non-mammary carcinomas and were speculated to overall represent a proinflammatory response associated with the disease. Dogs with distant metastatic disease exhibited increased fibrinogen and d-dimer. Future studies are needed to elucidate the clinical importance of these results.     

Methylation of free-floating deoxyribonucleic acid fragments in the bronchoalveolar lavage fluid of dogs with chronic bronchitis exposed to environmental tobacco smoke

Background

The etiology of canine chronic bronchitis (CB) is not completely understood, although exposure to environmental tobacco smoke (ETS) affects the airway inflammatory responses in some dogs with CB. The mechanism by which this occurs is unknown.

Findings

We investigated the concentrations and methylation rates of free-floating DNA fragments in bronchoalveolar lavage fluid (BALF) from dogs with chronic bronchitis. Based on serum cotinine levels, dogs with CB were divided into 2 groups: dogs that either had or had not been exposed to ETS. Our results demonstrated that the total nucleated cell and macrophage numbers increased in BALF of ETS-exposed dogs with CB. There were no significant differences in DNA concentrations and methylation rates in BALF between the 2 groups. However, 3 out of 8 dogs exposed to ETS had high DNA methylation rates in their BALF samples.

Conclusion

Our results suggest that ETS exposure leads to epigenetic modifications of cellular components in BALF in dogs diagnosed with CB.     

Morphological and immunohistochemical characterisation of seminomas in Norwegian dogs

Background

Seminomas in the dog have traditionally been assumed to resemble human spermatocytic seminomas, based on their low malignancy and high occurrence in old individuals. However, recently published studies indicate that canine seminomas can be classified as classical and spermatocytic seminomas in a similar way as in man, and that classical seminomas comprise a substantial proportion of seminomas in the dog. These two factors both contribute to increasing the potential of canine seminoma as a relevant model for human testicular cancer. The aim of the present study was to characterise seminoma in Norwegian dogs using morphology and immunohistochemistry, and determine whether these tumours are comparable with human classical seminoma.

Methods

By applying diagnostic criteria from human pathology, 45 seminomas from the Norwegian Canine Cancer Register were examined histologically with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) stains. All sections were stained immunohistochemically with antibodies against human placental alkaline phosphatase (PLAP) and the transmembrane receptor c-KIT.

Results

Although two of the seminomas showed immunohistochemical staining characteristics indicative of classical seminoma (PLAP+/c-KIT+), all 45 examined seminomas were morphologically consistent with spermatocytic seminoma.

Conclusions

The value of canine seminoma as a model for SE in man remains unclear. Among the 45 investigated tumours from Norwegian dogs, none were classified as classical seminoma based on morphological criteria consistent with human seminomas. Regional or breed differences in the occurrence of classical seminoma in the dog, as well as the lack of uniform diagnostic criteria, might explain the discrepancy between the findings in the current study and the results presented by other authors.     

A longitudinal study on diarrhoea and vomiting in young dogs of four large breeds

Background

Prospective studies to document the occurrence of canine diarrhoea and vomiting are relatively scarce in dogs, and the majority of published studies are based on information from clinical records. This study investigates the incidence risk of diarrhoea and vomiting as well as potential risk factors.

Methods

A cohort study of 585 privately owned dogs of four breeds: Newfoundland, Labrador retriever, Leonberger, and Irish wolfhound. The owners maintained a continuous log regarding housing, exercise, nutrition, and health of their dogs. Episodes of diarrhoea and vomiting were recorded in a consecutive manner in a booklet. The owners completed the questionnaires and reported information at three, four, six, 12, 18, and 24/25 months of age, called observational ages.Associations with potential risk factors for diarrhoea and vomiting were investigated in separate generalized estimating equation analyses.

Results

The incidence of both diarrhoea and vomiting was influenced by breed. Both diarrhoea and vomiting were relatively common in young dogs, occurring most frequently during the first months of life. After three months of age, the odds of diarrhoea were significantly lower when compared to the observational period seven weeks to three months (OR ranging from 0.31 to 0.70 depending on the period). More males than females suffered from diarrhoea (OR = 1.42). The occurrence of diarrhoea was more common in dogs that also experienced episode(s) of vomiting during the study period (OR = 5.43) and vice versa (OR = 5.50). In the majority of dogs episodes of diarrhoea and vomiting did not occur at the same time. Dogs in urban areas had higher odds (OR = 1.88) of getting diarrhoea compared to dogs living in rural areas. The occurrence of both diarrhoea and vomiting demonstrated a seasonal variation with higher incidence during the summer months.

Conclusion

Both diarrhoea and vomiting occurred most frequently during the first months of life. The incidence of diarrhoea and vomiting was significantly different between breeds. Diarrhoea occurred more frequently in males and in dogs living in urban areas. Also, a positive association between the occurrence of diarrhoea and vomiting in the same dog was found.     

Cross-reactivity of commercially available anti-human monoclonal antibodies with canine cytokines: establishment of a reliable panel to detect the functional profile of peripheral blood lymphocytes by intracytoplasmic staining

Background

The process for obtaining monoclonal antibodies against a specific antigen is very laborious, involves sophisticated technologies and it is not available in most research laboratories. Considering that most cytokines remain partially conserved among species during evolution, the search for antibody cross-reactivity is an important strategy for immunological studies in veterinary medicine. In this context, the amino acid sequence from human and canine cytokines have demonstrated 49–96 % homology, suggesting high probability of cross-reactivity amongst monoclonal antibodies. For this, 17 commercially available anti-human monoclonal antibodies [IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8 (#1, #2), IL-10, IL-12, IL-13, IL-17A, IFN-γ (#1, #2), TNF-α (#1, #2) and TGF-β], were evaluated in vitro for intracellular cytokine detection in a stimulated canine blood culture by flow cytometry and confocal microscopy. Lymphocytes from peripheral blood of healthy and two unhealthy dogs were analyzed.

Results

Eleven anti-human mAbs [IL-1α, IL-4, IL-5, IL-6, IL-8 (#1, #2), IL-12, IL-17A, TNF-α (#1, #2) and TGF-β] cross-reacted against canine intracellular cytokines. The specificity of the assays was not affected after Fc-blocking. Three anti-human cytokine mAbs [IL-4, IL-8 (#2) and TGF-β] when evaluated by confocal microscopy also cross-reacted with intracellular canine cytokines. The identification of human mAbs that cross-reacted with canine cytokines may support their use as immunological biomarkers in veterinary medicine studies.

Conclusion

The identification of these 11 anti-human cytokine mAbs that cross-reacted with canine cytokines will be useful immunological biomarkers for pathological conditions by flow cytometry and fluorescence microscopy in dogs.     

No evidence of horizontal infection in horses kept in close contact with dogs experimentally infected with canine influenza A virus (H3N8)

Background

Since equine influenza A virus (H3N8) was transmitted to dogs in the United States in 2004, the causative virus, which is called canine influenza A virus (CIV), has become widespread in dogs. To date, it has remained unclear whether or not CIV-infected dogs could transmit CIV to horses. To address this, we tested whether or not close contact between horses and dogs experimentally infected with CIV would result in its interspecies transmission.

Methods

Three pairs of animals consisting of a dog inoculated with CIV (10^8.3 egg infectious dose₅₀/dog) and a healthy horse were kept together in individual stalls for 15 consecutive days. During the study, all the dogs and horses were clinically observed. Virus titres in nasal swab extracts and serological responses were also evaluated. In addition, all the animals were subjected to a gross pathological examination after euthanasia.

Results

All three dogs inoculated with CIV exhibited clinical signs including, pyrexia, cough, nasal discharge, virus shedding and seroconversion. Gross pathology revealed lung consolidations in all the dogs, and Streptococcus equi subsp. zooepidemicus was isolated from the lesions. Meanwhile, none of the paired horses showed any clinical signs, virus shedding or seroconversion. Moreover, gross pathology revealed no lesions in the respiratory tracts including the lungs of the horses.

Conclusions

These findings may indicate that a single dog infected with CIV is not sufficient to constitute a source of CIV infection in horses.     

Plasma creatinine in dogs: intra- and inter-laboratory variation in 10 European veterinary laboratories

Background

There is substantial variation in reported reference intervals for canine plasma creatinine among veterinary laboratories, thereby influencing the clinical assessment of analytical results. The aims of the study was to determine the inter- and intra-laboratory variation in plasma creatinine among 10 veterinary laboratories, and to compare results from each laboratory with the upper limit of its reference interval.

Methods

Samples were collected from 10 healthy dogs, 10 dogs with expected intermediate plasma creatinine concentrations, and 10 dogs with azotemia. Overlap was observed for the first two groups. The 30 samples were divided into 3 batches and shipped in random order by postal delivery for plasma creatinine determination. Statistical testing was performed in accordance with ISO standard methodology.

Results

Inter- and intra-laboratory variation was clinically acceptable as plasma creatinine values for most samples were usually of the same magnitude. A few extreme outliers caused three laboratories to fail statistical testing for consistency. Laboratory sample means above or below the overall sample mean, did not unequivocally reflect high or low reference intervals in that laboratory.

Conclusions

In spite of close analytical results, further standardization among laboratories is warranted. The discrepant reference intervals seem to largely reflect different populations used in establishing the reference intervals, rather than analytical variation due to different laboratory methods.     

Associations among systemic blood pressure,microalbuminuria and albuminuria in dogs affected with pituitary- and adrenal-dependent hyperadrenocorticism

Background

Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).

Methods

This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).

Results

Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).

Conclusions

Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.     

The characteristics of short- and long-term surviving Shiba dogs with chronic enteropathies and the risk factors for poor outcome

Background

The objectives of this study were to investigate the differences in the characteristics of short- and long-term surviving dogs, and the factors that predict poor outcome in Shiba dogs with chronic enteropathies (CE).

Methods

A total of 25 Shiba dogs were included in this study, and classified as either short-term (≤6 months) survivors (Ss; n=16) or long-term (>6 months) survivors (Ls; n=9). The clinical and clinicopathological variables, histopathology, response to therapy, and outcomes were investigated between groups. Furthermore, these factors were tested for their ability to predict poor outcome.

Results

All CE dogs were diagnosed as having inflammatory bowel disease (IBD) with lymphocytic-plasmacytic enteritis (LPE). Age and canine inflammatory bowel disease activity index (CIBDAI) were significantly higher in the Ss group than in the Ls group (age: p = 0.035, CIBDAI: p = 0.018), as determined via univariate logistic regression analysis. According to receiver operator characteristic (ROC) curve analysis, the best predictors of poor outcome were age and CIBDAI, with the cutoffs determined as 7 years and 9 points, respectively. The majority of the cases (84%) responded to initial treatment; in particular, 75% of dogs in Ss group responded to therapy. The time to response (days) to the initial treatment in the Ss group (median 42.5 days, range: 20-91 days) was significantly shorter than that of the Ls group (median 285 days, range: 196-1026 days). Approximately half (55.5%) of the dogs in the Ls group died due to relapse of CE.

Conclusions

This study suggested that there is a high risk of early mortality in Shiba dogs with CE, particularly if the dogs are older (>7 years) and have a high CIBDAI score (>9 points). There appears to be a possibility of early mortality even if the initial treatment was efficacious. Furthermore, Shiba dogs with CE that become less responsive to initial therapy in the short-term (approximately 3 months) are more likely to have an early mortality. Thus, it is necessary to follow-up Shiba dogs with CE in the long-term, as approximately half of the long-term survivors eventually died due to a relapse of the signs.     

Seroprevalence against Borrelia burgdorferi sensu lato and occurence of antibody co-expression with Anaplasma phagocytophilum in dogs in Latvia

Background

Lyme disease is commonly diagnosed in humans in Latvia, but up to date no studies have been performed to investigate its prevalence in dogs. The aim of this study was to evaluate if seroprevalence against B. burgdorferi sensu lato (B. burgdorferi s.l.) and co-expression of antibodies against B.burgdorferi s.l. and A. phagocytophilum is higher in dogs with clinical suspicion of tick-borne diseases compared to healthy dogs.

Findings

Venous blood was taken from healthy dogs (n=441) and dogs suspected to have borreliosis and/ or canine granulocytic anaplasmosis (n=29). The presence of antibodies was detected with SNAP 4Dx test (IDEXX, Westbrook, Maine, USA). The seroprevalence against B. burgdorferi s.l. in healthy dogs was 2.49% (11/441) and 36% (4/11) of seropositive dogs had antibodies against both of investigated bacteria. None of the dogs in sick dog group had detectable antibodies against B. burgdorferi s.l.

Conclusions

We conclude that seroprevalence to B. burgdorferi s.l. in dogs in Latvia is low and that dogs with suspicion of tick-borne disease do not have higher B. burgdorferi s.l. seroprevalence than healthy dogs. Dogs that express antibodies against B. burgdorferi s.l. frequently co-express antibodies against A. phagocytophilum.     

Oral malignant melanomas and other head and neck neoplasms in Danish dogs - data from the Danish Veterinary Cancer Registry

Background

Head and neck cancers (HNC) are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM) is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model.

Methods

Canine cases entered in the Danish Veterinary Cancer Registry (DVCR) from May 15th 2005 through February 29th 2008 were included in this study. Fisher''s exact test was used to compare proportions of HNC in dogs and humans as well as proportions of surgically treated cases of OMM and squamous cell carcinomas (SCC). Also the proportions of benign and malignant neoplasms of different locations in dogs were compared using Fisher''s exact test.

Results

A total of 1768 cases of neoplasias (679 malignant, 826 benign, 263 unknown) were submitted. Of all neoplasias HNC accounted for 7.2% (n = 128). Of these, 64 (50%) were malignant and 44 (34%) benign. The most common types of malignant neoplasia were SCC (18; 28% of malignant), OMM (13; 20% of malignant), soft tissue sarcoma (11; 17% of malignant) and adenocarcinoma (5; 11% of malignant). The most common types of benign neoplasms were adenoma (7; 16% of benign), polyps (6; 14% of benign) and fibroma (5; 11% of benign).

Conclusions

In the current study, the proportion of neoplasia in the head and neck region in dogs in Denmark was similar to other canine studies and significantly more common than in humans with a large proportion of malignancies. Spontaneous HNC in dogs thus, may serve as a model for HNC in humans.Canine OMM is a spontaneous cancer in an outbred, immune-competent large mammal population and could be a clinical model for OMM in humans.     

Effect of tylosin on dogs with suspected tylosin-responsive diarrhea: a placebo-controlled,randomized, double-blinded,prospective clinical trial

Background

The macrolid antibiotic tylosin has been widely used to treat canine chronic diarrhea, although its efficacy is based on anecdotal reports and experimental studies in dogs and not on strong scientific evidence. The term tylosin-responsive diarrhea (TRD) refers to diarrheal disorders responding to tylosin therapy within a few days. In TRD, the stool remains normal as long as tylosin treatment continues, but diarrhea reappears in many dogs within weeks after discontinuation. The aim of our trial was to assess the effect of tylosin on fecal consistency compared with a placebo treatment in dogs with suspected TRD and additionally to establish whether tylosin in dogs with recurrent diarrhea is as effective as empirical studies and anecdotal reports suggest.

Methods

Subjects comprised 71 client-owned dogs that, according to the owners, had previously been treated successfully with tylosin due to recurrent diarrhea of unknown etiology. At the initial examination, where there were no signs of diarrhea, the dogs were randomly assigned in a 2:1 ratio to a tylosin or placebo group. During a two-month follow-up the owners evaluated the fecal consistency according to previously published guidelines. When diarrhea recurred, either tylosin (25 mg/kg q 24 h, 7 days) or placebo treatment was initiated orally. Treatment outcome was evaluated as the mean of fecal consistency scores assigned during the last three days of the treatment period. To test for differences between the tylosin and placebo group in the proportion of responders, Pearson''s Chi-squared test and Fisher''s exact test were applied.

Results

Sixty-one dogs met the selection criteria and were followed for two months. During the follow-up 27 dogs developed diarrhea and either tylosin or placebo treatment was started. The proportion of dogs with normal fecal consistency at the end of treatment was 85% (17/20) in the tylosin group and 29% (2/7) in the placebo group (Pearson''s Chi-squared test p = 0.0049 and Fisher''s exact test two-sided, p = 0.0114).

Conclusions

Our findings indicate that tylosin is effective in treating recurrent diarrhea in dogs. The dose of 25 mg/kg once daily appears sufficient. No changes specific to TRD were detected in the examinations.     

Mast cell tumours and other skin neoplasia in Danish dogs - data from the Danish Veterinary Cancer Registry

Background

The Danish Veterinary Cancer Registry (DVCR) was established in May 2005 to gather information about neoplasms in the Danish dog and cat populations. Practitioners from more than 60 clinics throughout Denmark have submitted data on these species. The objectives of the current study were, with a special focus on mast cell tumours (MCT) to investigate the occurrence, gender distribution, biological behaviour, locations, types, the diagnostic method used and treatment of skin neoplasms in dogs based on information reported to the DVCR.

Methods

From May 15^th 2005 through February 29^th 2008, reports on a total of 1,768 canine cases of neoplasia in the skin, subcutis or adnexa were submitted.) Of these, 765 cases (43%) were confirmed by cytology or histopathology.

Results

The majority of dogs had a benign neoplasm (66%) while 21% were cases of malignant neoplasia. The most commonly encountered malignant neoplasms were MCT and soft tissue sarcomas and for benign neoplasms, lipomas and histiocytomas were the most common. The location of the neoplasms were primarily in the cutis, subcutis or in the perianal region. The occurrence, gender distribution, biological behaviour and location of canine skin neoplasias in Denmark were similar to earlier reports, although some national variations occurred. A correlation between grade of MCT and the proportion of cases treated surgically was observed.

Conclusions

Population based cancer registries like the DVCR are of importance in the collection of non-selected primary information about occurrence and distribution of neoplasms. The DVCR provides detailed information on cases of skin neoplasms in dogs and may serve as a platform for the study of sub-sets of neoplastic diseases (e.g. MCT) or subgroups of the canine population (e.g. a specific breed).     

The first report of autochthonous non-vector-borne transmission of canine leishmaniosis in the Nordic countries

Background

Leishmania spp. are zoonotic protozoans that infect humans and other mammals such as dogs. The most significant causative species in dogs is L. infantum. In dogs, leishmaniosis is a potentially progressive, chronic disease with varying clinical outcomes. Autochthonous cases of canine leishmaniosis have not previously been reported in the Nordic countries.

Results

In this report we describe the first diagnosed autochthonous cases of canine leishmaniosis in Finland, in which transmission via a suitable arthropod vector was absent. Two Finnish boxers that had never been in endemic areas of Leishmania spp., had never received blood transfusions, nor were infested by ectoparasites were diagnosed with leishmaniosis. Another dog was found with elevated Leishmania antibodies. A fourth boxer dog that had been in Spain was considered to be the source of these infections. Transmission occurred through biting wounds and semen, however, transplacental infection in one of the dogs could not be ruled out.Two of the infected dogs developed a serious disease and were euthanized and sent for necropsy. The first one suffered from membranoproliferative glomerulonephritis and the second one had a chronic systemic disease. Leishmania sp. was detected from tissues by PCR and/or IHC in both dogs. The third infected dog was serologically positive for Leishmania sp. but remained free of clinical signs.

Conclusions

This case report shows that imported Leishmania-infected dogs may pose a risk for domestic dogs, even without suitable local arthropod vectors.     

Argyrophilic nucleolar organizing regions and Ki67 equally reflect proliferation in fine needle aspirates of normal, hyperplastic, inflamed, and neoplastic canine lymph nodes (n = 101)

BACKGROUND: The count of argyrophilic nucleolar organizing regions (AgNOR) has been considered a useful variable that reflects cellular proliferation in canine lymph nodes, but it has not been compared with other markers of proliferation. Hypothesis: Ki67 and AgNORs are equally useful as markers of tissue proliferation in fine needle aspirates of canine lymph nodes. ANIMALS: A total of 101 dogs. MATERIAL AND METHODS: Prospective, observational study of a convenience sample of dogs. Two smears were prepared for a May-Gruenwald-Giemsa stain and a Ki67/AgNOR double stain. In addition, CD3/CD79a immunostaining was performed when cytologic examination revealed a lymphoma. The dogs were grouped as normal (n = 26), reactive hyperplasia (n = 25), lymphadenitis (n = 31), and lymphoma (n = 19), based on the physical examination and the cytologic findings. The AgNOR count/cell, AgNOR area/cell and the percentage of cells staining positive for Ki67 were evaluated in 100-167 cells (median, 113 cells) by using automatic image analysis. RESULTS: Mean (SD) AgNOR counts/cell were 1.36 +/- 0.19 in normal dogs, 1.55 +/- 0.26 in lymphadenitis, 1.65 +/- 0.32 in reactive hyperplasia, and 3.67 +/- 1.08 in lymphoma. The percentage of Ki67 positive cells was 2.67 +/- 0.99% in normal lymph nodes, 5.04 +/- 3.34% in lymphadenitis, 5.36 +/- 2.14% in reactive hyperplasia, and 30.2 +/- 10.8% in lymphoma. All variables were significantly higher in dogs with lymphoma compared with the other groups (P < .0001). The sensitivity and the specificity of the AgNOR count for diagnosing lymphoma were 95 and 96% at a cutoff value of >2.04 AgNORs/cell. The cutoff value for the Ki67 positive cells was >10.40% (sensitivity, 95%; specificity, 98%). CONCLUSION AND CLINICAL IMPORTANCE: The results indicated that both AgNOR and Ki67 counts were good diagnostic tools for assessment of proliferation in aspirates of canine lymph nodes.