A longitudinal study of the blood and urine metabolome of Vipera berus envenomated dogs.

Envenomation of dogs by the common European adder (Vipera berus) is associated with high morbidity. The cytotoxic venom of Vipera berus contains enzymes with the potential to cause acute kidney injury, among other insults, however robust biomarkers for such effects are lacking. A prospective observational follow-up study of naturally envenomated dogs and controls was conducted to fill knowledge gaps regarding canine Vipera berus envenomation, attempt to identify novel biomarkers of envenomation and related kidney injury, and elucidate potential long-term effects. Blood and urine samples were analyzed with a global metabolomics approach using liquid chromatography-mass spectrometry, uncovering numerous features significantly different between cases and controls. After data processing and feature annotation, eight features in blood and 24 features in urine were investigated in order to elucidate their biological relevance. Several of these are associated with AKI, while some may also originate from disturbed fatty acid ß-oxidation and soft tissue damage. A metabolite found in both blood and a venom reference sample may represent identification of a venom component in case dogs. Our findings suggest that envenomated dogs treated according to current best practice are unlikely to suffer permanent injury.

Serial serum creatinine, SDMA and urinary acute kidney injury biomarker measurements in dogs envenomated by the European adder (Vipera berus).

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) and symmetric dimethylarginine (SDMA) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated by V. berus at 12, 24 and 36 h after bite, as well as 14 days later, using sCr, SDMA and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs. RESULTS: Thirty-five envenomated dogs and 35 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Serum SDMA did not exceed 0.89 µmol/L in any dog. Compared to controls, urinary albumin/uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1/uCr were significantly elevated 12 h (P <  0.0001, P <  0.0001, P = 0.01), 24 h (P <  0.001, P <  0.001, P = 0.002) and 36 h (P <  0.001, P <  0.001, P = 0.0008) after bite. Osteopontin/uCr was higher 24 and 36 h after bite (P < 0.0001), kidney injury molecule-1/uCr, interleukin-8/uCr and γ- glutamyl transferase/uCr were significantly higher 36 h after bite (P = 0.003, P = 0.0005, P = 0.001). Urinary cystatin C/uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls. CONCLUSION: Urinary biomarker/Cr ratios are indicative of mild transient, non-azotaemic AKI in dogs envenomated by V. berus.

Risk factors for idiopathic cystitis in Norwegian cats: a matched case-control study.

OBJECTIVES: The aim of the study was to compare a group of cats with feline idiopathic cystitis (FIC) with a group of control cats without present or previous signs of lower urinary tract disease in order to identify factors in characteristics, personality, behaviour, environment and daily life that would make them more susceptible to the disease. METHODS: The study was a matched case-control study comparing results from telephone interviews based on a standardised questionnaire. The questions were organised into six subject groups: the characteristics of the cat; the cat's environment; the presence of other pets in the household; the cat's feeding and drinking regime; management of the cat's litter box; and the cat's opportunity to perform natural behaviour. RESULTS: The results from the present study showed that a cat diagnosed with FIC was more likely to be overweight and to be of a nervous disposition than the control cats. In addition, several differences between cases and controls were detected at a univariable level of analysis, related to outdoor access and the cats' perceived safety and comfort in their home environments. While not significant after multivariable analysis, these variables may still be of importance owing to potential interrelations. CONCLUSIONS AND RELEVANCE: Several significant differences between cats with FIC and control cats were revealed, and the results support the hypothesis of environmental stress as being a potential factor in the development of FIC.

Age-related changes in hematologic and serum biochemical variables in dogs aged 16-60 days.

BACKGROUND: The literature reporting hematologic and serum biochemical variables in puppies is limited. As puppies are physiologically different from adult dogs, an age effect would be expected. OBJECTIVES: We aimed to describe age-related changes in hematologic and serum biochemical variables in puppies aged 16-60 days and compare the results to reference intervals (RI) for adults. Our second aim was to determine RI for this age group. METHODS: A total of 227 blood samples were collected from 101 clinically healthy puppies, mainly mixed breeds. To assess the effect of age, the results were compared to RI for adult dogs, and variations within the age period 16-60 days were studied. Reference intervals for the groups 16-24, 28-45, and 46-60 days of age were determined. RESULTS: Lower values in puppies compared to adults were found for RBC, HGB, HCT, concentration of albumin, globulin, total protein, creatinine, and sodium:potassium ratio. Higher values in puppies compared to adults were found for activities of ALP and CK, and concentrations of inorganic phosphorus, calcium, and potassium. For MCV, MCHC, albumin:globulin ratio, and glucose concentration, different values in puppies compared to adults were found for some of the age groups. No age-specific differences were found compared to RI for adults regarding WBC, absolute counts of lymphocytes, neutrophils, monocytes, eosinophils, and platelets, RDW, activities for AST, ALT, amylase, lipase, and concentrations of bile acids, cholesterol, urea, sodium, and chloride. CONCLUSIONS: Our results support that age has a significant effect on several hematologic and serum biochemical values in puppies, warranting age-specific RI.

Prevalence of and risk factors for increased serum levels of allergen-specific IgE in a population of Norwegian dogs.

BACKGROUND: The importance of different allergens in association with IgE production and canine atopic dermatitis (CAD) has been poorly studied and few studies exist on factors influencing allergen-specific IgE antibodies in serum. The aim of this cross-sectional study was to investigate the prevalence of elevated IgE levels to different environmental allergens in Norwegian dogs with a suspicion of CAD. The secondary aim was to identify risk factors associated with elevated serum levels of allergen-specific IgE. RESULTS: The study sample consisted of serum from 1313 dogs of 161 different breeds. All samples were submitted for serologic IgE-testing (Fc epsilon R1 alpha-based ELISA) based on suspicion of CAD. Overall, 84.3% of the dogs had elevated IgE levels to one or more of the allergen(s). The predominant allergens amongst the positive results were the indoor allergens (Acarus siro 84.0%, Dermatophagoides farinae 80.2%, Tyrophagus putrescentiae 79.9%). Sheep sorrel was the most commonly encountered outdoor allergen (40.0%). Only 2.6% of the dogs with elevated IgE levels were positive to flea saliva. The test results varied significantly depending on when the serum samples were taken. Samples taken during summer and autumn more often came out positive than samples taken during winter and spring. Geographical variations were also demonstrated. A greater proportion of females than males had positive test results, and more females than males tested positive to outdoor allergens. The mean age was significantly higher in the dogs testing positive than amongst the dogs testing negative. The allergen-specific IgE levels varied with breed. The boxer was the only breed with a significantly higher proportion of positive test results compared to the other breeds. Boxers also had a higher prevalence of elevated IgE levels to outdoor allergens, whereas the Rottweiler had a higher prevalence of elevated IgE levels to indoor allergens compared to the other breeds. CONCLUSIONS: IgE hypersensitivity was most often associated with indoor allergens. Outdoor allergens were of minor importance and IgE reactivity to flea saliva was rare. Breed differences in allergen-specific IgE levels were identified. Season of sampling, and the dogs' geographical localisation, sex and age also affected the results of the IgE analysis.

Dirofilaria repens infection in a dog imported to Norway.

Dirofilaria repens infection was diagnosed in a dog that had been imported to Norway from Hungary three years previously. The dog was a four-year-old castrated male mixed-breed dog and presented for examination of two masses on the right thoracic wall. Fine needle sampling from the subcutaneous nodules and subsequent cytological examination revealed a high number of microfilariae and a pyogranulomatous inflammation. At re-examination approximately 3 weeks later, both masses had apparently disappeared spontaneously, based on both inspection and palpation. However, examination of peripheral blood by a modified Knott's test revealed a high number of unsheathed microfilariae with mean length of 360 µm and mean width of 6-7 µm, often with the classic umbrella handle appearance of D. repens. Polymerase chain reaction and sequencing confirmed the D. repens diagnosis. Subcutaneous dirofilariosis caused by D. repens is probably the most common cause of human zoonotic dirofilariosis in Europe, but currently is rarely encountered in northern countries such as Norway. However, travelling, import and relocation of dogs have increased, and thus the geographical range of these parasites is likely to increase from traditionally endemic southern regions. Increasing numbers of autochthonous cases of D. repens infections in dogs have been reported in eastern and central Europe. Although infection with D. repens often induces only mild signs or subclinical infections in dogs, they nevertheless represent a reservoir for zoonotic transmission and thus a public health concern, and, in addition, due to the long prepatent period and the high frequency of subclinical infections or infections with unspecific clinical signs, could easily be missed. Lack of experience and expectation of these parasites may mean that infection is underdiagnosed in veterinary clinics in northern countries. Also, predicted climate changes suggest that conditions in some countries where this infection is currently not endemic are likely to become more suitable for development in the intermediate host, and thus the establishment of the infection in new areas.

Housing- and exercise-related risk factors associated with the development of hip dysplasia as determined by radiographic evaluation in a prospective cohort of Newfoundlands, Labrador Retrievers, Leonbergers, and Irish Wolfhounds in Norway.

OBJECTIVE: To identify housing- and exercise-related risk factors associated with the development of hip dysplasia (HD) as determined by radiographic evaluation in Newfoundlands, Labrador Retrievers, Leonbergers, and Irish Wolfhounds in Norway. ANIMALS: 501 client-owned dogs from 103 litters. PROCEDURES: Dogs were assessed from birth until official radiographic screening for HD at 12 (Labrador Retriever [n = 133] and Irish Wolfhound [63]) or 18 (Newfoundland [125] and Leonberger [180]) months of age. Information regarding housing and exercise conditions during the preweaning and postweaning periods was obtained with questionnaires. Multivariable random effects logistic regression models were used to identify housing- and exercise-related risk factors associated with the development of radiographically detectable HD. RESULTS: Puppies walking on stairs from birth to 3 months of age had an increased risk of developing HD. Factors associated with a decreased risk of developing HD included off-leash exercise from birth to 3 months of age, birth during the spring and summer, and birth on a farm. Significant clustering of dogs with HD was detected within litters. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that puppies ≤ 3 months old should not be allowed access to stairs, but should be allowed outdoor exercise on soft ground in moderately rough terrain to decrease the risk for developing radiographically detectable HD. These findings could be used as practical recommendations for the prevention of HD in Newfoundlands, Labrador Retrievers, Leonbergers, and Irish Wolfhounds.

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.

Risk factors for hip-related clinical signs in a prospective cohort study of four large dog breeds in Norway.

We conducted a prospective cohort study including privately owned dogs from the breeds Newfondland (NF), Labrador Retriever (LR), Leonberger (LEO), and Irish Wolfhound (IW) followed from birth until age 9 yrs. We wanted to investigate whether radiological hip dysplasia status given at approximately age 12-18 mos and other factors during growth influenced development of clinical signs due to hip-joint disease necessitating veterinary consultation. Whether or not such signs occurred due to hip dysplasia or due to secondary or primary DJD could not be distinguished, and we therefore used the term "owner-reported veterinary-diagnosed hip-related clinical signs" ("the event"). The included dogs were followed from birth to the event or until a maximum of 9 yrs of age. Our objectives were to describe breed differences in time to incidence and to evaluate potential risk factors for the time to event. We used Kaplan-Meier curves to describe time to incidence, and potential risk factors were assessed by use of a Cox proportional-hazards model. We enrolled 494 dogs from 103 litters, and 46 dogs were reported as having had the event during the observation period. We observed a significant time-varying effect (TVE): LR and LEO developed clinical signs later in life than NF. If the radiological hip status was either mild, moderate, or severe the hazard of experiencing the event was significantly increased. Access to off-leash exercise at age 12 mos decreased the hazard of the event, and the hazard varied by litter. The findings supported the hypothesis that radiological hip status at screening and exercise conditions during growth influenced the time to incidence of the event and that there were breed differences in time to the event.

The effect of radiological hip dysplasia and breed on survival in a prospective cohort study of four large dog breeds followed over a 10 year period.

The aim of the study was to measure the effect of radiological hip and elbow dysplasia status and breed on overall survival in a cohort of four large dog breeds in Norway. Privately owned dogs of the Newfoundland (NF), Labrador Retriever (LR), Leonberger (LEO), and Irish Wolfhound (IW) breeds were followed prospectively from birth to 10 years of age. The age of death/euthanasia was registered. A total of 501 dogs from 103 litters were enrolled. Kaplan-Meier survival curves were used to describe breed differences in survival times. The effects of radiological hip and elbow dysplasia status as well as breed were assessed using a Cox proportional hazards model. The variables 'sex' and 'living region' were explored as potential confounders. Among LRs, 60.2% of the dogs were still alive at 10 years of age, and the corresponding figures for NFs, LEOs, and IWs were 28.8%, 16.11%, and 6.4%, respectively. Radiological hip dysplasia status and breed were found to influence overall survival. Two different time-varying effects were observed in that with the IW the hazard of death increased linearly through time, while the effect of severe radiological hip dysplasia decreased logarithmically with time. Location influenced the death hazard and dogs living in suburban areas or cities had longer mean time to death and a lower hazard compared to dogs living in the countryside. Radiological elbow dysplasia status was not found to have an effect on overall survival.

Occurrence of occult bacteriuria in healthy cats.

Knowledge of the occurrence of bacteriuria in adult, healthy cats is scarce in the scientific literature. A study was designed to investigate the occurrence of bacteriuria in healthy cats without current or previous signs of lower urinary tract disease. The study included 108 cats, 53 males (49.5%) and 55 females (50.5%). The cats ranged in age between 7 months and 18 years, with a mean age of 4.4 years and a median age of 4.0 years. Urine was obtained by cystocentesis from all the cats, and was submitted for bacteriological analyses. Urine and urine sediment was cultured on separate blood agar plates for quantification and species identification by standard procedures. Detection of ≥10(3)colony forming units (cfu) per ml urine was defined as significant bacteriuria. Significant bacteriuria exceeding 10(5) cfu/ml was detected in one sample with a combination of Enterococcus species and Staphylococcus species. There was no bacterial growth in the urine samples from 107 cats (99.1%). Results from our study indicate that the prevalence of bacteriuria in clinically healthy, adult cats is low. Also, that contamination of samples is rare when urine is collected by cystocentesis.

Multi-source analysis reveals latitudinal and altitudinal shifts in range of Ixodes ricinus at its northern distribution limit.

BACKGROUND: There is increasing evidence for a latitudinal and altitudinal shift in the distribution range of Ixodes ricinus. The reported incidence of tick-borne disease in humans is on the rise in many European countries and has raised political concern and attracted media attention. It is disputed which factors are responsible for these trends, though many ascribe shifts in distribution range to climate changes. Any possible climate effect would be most easily noticeable close to the tick's geographical distribution limits. In Norway- being the northern limit of this species in Europe- no documentation of changes in range has been published. The objectives of this study were to describe the distribution of I. ricinus in Norway and to evaluate if any range shifts have occurred relative to historical descriptions. METHODS: Multiple data sources - such as tick-sighting reports from veterinarians, hunters, and the general public - and surveillance of human and animal tick-borne diseases were compared to describe the present distribution of I. ricinus in Norway. Correlation between data sources and visual comparison of maps revealed spatial consistency. In order to identify the main spatial pattern of tick abundance, a principal component analysis (PCA) was used to obtain a weighted mean of four data sources. The weighted mean explained 67% of the variation of the data sources covering Norway's 430 municipalities and was used to depict the present distribution of I. ricinus. To evaluate if any geographical range shift has occurred in recent decades, the present distribution was compared to historical data from 1943 and 1983. RESULTS: Tick-borne disease and/or observations of I. ricinus was reported in municipalities up to an altitude of 583 metres above sea level (MASL) and is now present in coastal municipalities north to approximately 69°N. CONCLUSION: I. ricinus is currently found further north and at higher altitudes than described in historical records. The approach used in this study, a multi-source analysis, proved useful to assess alterations in tick distribution.

Causes of lower urinary tract disease in Norwegian cats.

A study was made on causes of lower urinary tract disease in cats, and to investigate whether demographic data and factors related to husbandry might influence the occurrence of a particular diagnosis. The study was a prospective, descriptive, and analytical study of primary cases of feline lower urinary tract disease (FLUTD) in Norway. Only cats sampled by cystocentesis were included in the present study. Of the 119 cats included, 28.6% were diagnosed with obstructive FLUTD. The majority of cats were diagnosed with feline idiopathic cystitis (FIC) (55.5%). Urethral plugs were the second most common diagnosis (21.0%), whereas bacterial cystitis and urolithiasis each were diagnosed in 11.8%. Nearly one-third (28.6%) of the cats diagnosed with urolithiasis had significant bacteriuria. Thus, significant bacteriuria was diagnosed in a total of 15.1% of the cats. There were no significant differences in the urine specific gravity, pH and amount of epithelial cells in the urine sediment in the different aetiological categories of FLUTD. There was a higher amount of red blood cells in the urine sediment in cats diagnosed with urethral plugs and urolithiasis, whereas cats with bacterial cystitis and urolithiasis had a higher amount of white blood cells in their sediment. Regarding demographic data and factors related to husbandry, cats diagnosed with FLUTD were more often males and kept strictly indoors, when compared with a 'reference population'.

A prospective study on canine hip dysplasia and growth in a cohort of four large breeds in Norway (1998-2001).

The study-objective was to measure the effect of weight and growth related parameters on the risk of development of Canine Hip Dysplasia (CHD). The hypothesis was that heavy and fast growing dogs of large sized breeds were at increased risk of development of CHD compared to lighter and slower growing dogs. A prospective cohort study was conducted among dogs of four large breeds: Newfoundland (NF), Leonberger (LEO), Labrador retriever (LR), and Irish wolfhound (IW). The dogs were privately owned with individualized nutrition and environment, and they were followed from birth and throughout the growth period until the official screening for CHD was performed. The study sample consisted of 501 dogs from 103 litters, with the breed distribution 125 NF, 180 LEO, 133 LR, and 63 IW. Because the dogs were clustered in litters a multivariable random effects logistic regression model was used to assess statistically significant growth-related risk factors for CHD. The estimated incidence risk of CHD was 36% in NF, 25% in LEO, 20% in LR, and 10% in IW. Based upon the final multilevel model it appears that the odds of CHD among both LR and IW (odds ratio (OR) 0.22) are about one-fifth of the odds for NF. The odds for LEO (OR 0.60) are not significantly different from NF. There appeared to be an inverse relationship between body weight at 3 months of age and odds of CHD, with an OR of 0.89 (P=0.044). The degree of clustering at the litter-level was high (22.6%) and highly significant (P<0.001). Findings failed to support the hypothesis that heavy and fast growing dogs from four large sized breeds were at increased risk for development of CHD. There might be other unmeasured environmental risk factors for CHD in this cohort of dogs, although the contribution of the genetic variance to the litter-level clustering also needs further investigation.

A randomized, controlled study to evaluate the steroid sparing effect of essential fatty acid supplementation in the treatment of canine atopic dermatitis.

A randomized, double blind, placebo-controlled multicentre clinical trial of 12 weeks' duration was undertaken in 60 dogs with atopic dermatitis to evaluate the steroid sparing effect of essential fatty acid supplementation. The dogs were randomly assigned to receive either a combination of borage seed oil and fish oil or a placebo, in addition to prednisolone tablets. All dogs received a standardized basal diet. Owners of the dogs recorded pruritus daily using a 10 cm visual analog scale and the dosage of prednisolone was established based on the pruritus score, according to written instructions. The dosage of prednisolone and the use of any concurrent treatment (shampoo and/or ear-cleanser) were recorded by the owner on a daily basis. The investigators graded the skin lesions at days 0, 42 and 84. The use of prednisolone during the test period was lower in the active group, but the difference was not statistically significant (P = 0.32). The test period was sequentially divided into 43-84, 50-84, 57-84, 64-84, 71-84 and 78-84 days. On day 64, the difference between the active group and the placebo group reached statistical significance (P = 0.04) with an increasing difference towards the end of the study. A statistically significant reduction in the pruritus scores and the total clinical scores from day 0 to day 84 was apparent in both groups (P < 0.0001). At the end of the study, both the pruritus score and the total clinical score were lower in the active group. Our findings indicate a steroid sparing effect of essential fatty acid supplementation in canine atopic dermatitis and, furthermore, that there is a time lag before the effect is attained.