Diabetes mellitus in a population of 180,000 insured dogs: incidence, survival, and breed distribution

BACKGROUND: Canine diabetes mellitus (DM) is a common endocrinopathy with an unclear etiology. For a better understanding of the underlying mechanisms, there is a need for comprehensive epidemiologic studies. Earlier studies have shown that the risk of disease is higher in certain dog breeds. HYPOTHESIS: Incidence, age of onset, survival and sex proportion of DM vary by breed. ANIMALS: Data from a cohort of 182,087 insured dogs aged 5-12 years accounting for 652,898 dog-years at risk were studied retrospectively. METHODS: Incidence rates by sex, breed, and geography were calculated with exact denominators. Age-specific incidence and survival after 1st DM claim were computed with Cox's regression and Kaplan-Meier survival function. Multivariable survival analysis was performed for the outcome diagnosis of DM with age, sex, and geography tested as fixed effects, previous endocrine or pancreatic diseases tested as time-dependent covariates, and breed tested as a random effect. RESULTS: The mean age at 1st insurance claim for the 860 DM dogs (72% females) was 8.6 years. The incidence of DM was 13 cases per 10,000 dog-years at risk. Australian Terriers, Samoyeds, Swedish Elkhounds, and Swedish Lapphunds were found to have the highest incidence. The proportion of females with DM varied significantly among breeds. Swedish Elkhounds, Beagles, Norwegian Elkhounds, and Border Collies that developed DM were almost exclusively females. The multivariable model showed that breed, previous hyperadrenocorticism, and female sex were risk factors for developing DM. Median survival time was 57 days after 1st claim. Excluding the 223 dogs that died within 1 day, the median survival time was 2 years after 1st claim of DM. CONCLUSION: The significant breed-specific sex and age differences shown in this study indicate that genetic variation could make breeds more or less susceptible to different types of DM.     

Multiple cutaneous ganglioneuromas in a dog

A 3-year-old male Labrador retriever dog was presented with multifocal small cutaneous nodules, distributed mainly over the thoracic wall, the flank and the scrotum. The dog was otherwise in good health and had no significant past medical history. Radio- and sonographic examination revealed no evidence of internal tumours, including endocrine tumours. Histological examination of two excised samples revealed round, non-ulcerated nodules in the superficial corium, characterized by two different neoplastic cell components and mild inflammation. The first tumour cell population showed histomorphological characteristics of mature ganglion cells; the second featured small, spindle-shaped tumour cells with scant cytoplasm. Both neoplastic cell components expressed vimentin, neurofilament protein, pan-neuronal neurofilament, amyloid-precursor protein and chromogranin A. In addition, the spindle-shaped tumour cells were positive for 2', 3'-cyclicnucleotide 3'-phosphodiesterase. The findings had many histological and immunohistochemical features in common with primary cutaneous ganglioneuromas in humans, enabling the canine tumours to be also classified as multiple cutaneous ganglioneuromas.     

Clinical, cytogenetic and hormonal findings in a stallion with hypospadias--a case report

This case report describes a three-year-old Friesian stallion with hypospadias. Physical examination revealed a ventrocaudal deviation of the shaft of the penis and an incomplete glans penis. The urethral opening was 4 cm in length, slit-like and had a mucous membrane covering. A short fold ran from the ventral aspect of the anus and ended with a non-pigmented hairless area of skin. A human choriongonadotropin (hCG)-stimulation test resulted in an increase in the plasma levels of estrogen sulfate and testosterone, indistinguishable from that of a normal stallion. The karyogram had a normal number of chromosomes at 2n=64. The stallion was castrated, and histological evaluation of the testicular tissue was unremarkable. In contrast to other animal species and human beings, hypospadias is a rare congenital abnormality in stallions, the cause of which could not be elucidated in our patient.     

Study on biological variation of haemostatic parameters in clinically healthy dogs

Thromboelastography (TEG) may be a valuable supplement to the coagulation assays activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT) and D-Dimer currently used in most clinical pathology laboratories. Allowable imprecision and bias reference limits for analytical tests can be calculated based on measurements of biological variation. No studies to date have examined the effect of biological variation on these haemostasis parameters in the same group of dogs. Plasma samples were collected after a set protocol once weekly for five consecutive weeks from eight healthy dogs (four males and four females) and stored at -80 degrees C until analysis. Randomized duplicate coagulation tests and TEG analyses were performed on all plasma samples within one run. The data were analyzed for outliers and subsequently subjected to nested analysis of variance to obtain the coefficient of analytical, intra-individual and inter-individual variation. From these objective analytical performance standards for imprecision, critical difference, total error and the index of individuality were calculated to assess the utility of conventional population-based reference ranges. All the clotting times (aPTT, PT and TT), fibrinogen, AT and D-Dimer showed a degree of individuality, which may make the use of population-based reference ranges alone an insensitive interpretation criterion, whereas a population-based reference interval seems to be sensitive for interpreting all TEG parameters. Analytical performance standards for imprecision were only met for one of the coagulation assays, whereas all TEG parameters except the alpha angle, alpha achieved this analytical goal.     

Retrospective analysis of two phocine distemper epidemics in the North and Baltic Seas in 1988 and 2002

The relapse of the outbreak of the phocine distemper virus in the Danish island of Anholt this June, emphasizes the importance of the topic among experts. During the phocine distemper virus (PDV) epidemic in 1988, a total of 23,000 harbour seals (Phoca vitulina) died. In 2002 a second outbreak of PDV resulted in the death of more than 30,000 harbor seals. Both epidemics originated near the Danish island of Anholt and spread to adjacent colonies. Additional centres of infection were observed in the Dutch Wadden Sea far from the infected Danish seal populations. Arctic seals and grey seals were considered as vectors. Grey seal populations may serve as a reservoir for PDV or act as subclinically infected carriers of the virus between Arctic and North Sea seal populations. Mixed colonies of grey and harbour seals are widely distributed in the North and Baltic Seas. The role of environmental contaminants and their potential impact on immune function are discussed. The duration and geographical patterns of the two PDV epidemics are compared.     

Application of peracetic acid for the treatment of juvenile sander (Sander lucioperca) during Ichthyophthirius multifiliis infestation

White spot disease caused by the ciliate protozoan parasite Ichthyophthirius multifiliis (I. m.), is one of the most dangerous diseases in aquaculture and ornamental fish breeding worldwide. The parasite is characterized by three developmental stages: a reproductive tomont, an infective theront and a parasitic trophont. In sander (Sander lucioperca) breeding I. m. causes serious economic losses. After banning of the traditional therapeutic agent malachite green we have to face a state of emergency for the treatment of the ichthyophthiriasis in Germany. The peracetic acid (PAA), characterized by positive therapeutical properties, might close this gap. The purpose of our investigations was the determination of the toxicity of PES to juvenile sander as well as the evaluation of the therapeutic effectiveness of the substance to combat I. m. For juvenile sander (length 3 cm) we determined a 24-h-LC50 of 1.14 (0.97; 1.3) ppm PES. In two investigations PAA was applied in daily intervals of 0.5; 1, 3, 5 and 24 h and concentrations of 0.5; 1; 1.5 and 2 ppm to treat I.-m.-infection in sander. In test I all sander (length 9 cm) died as a result of the I.-m.-infection. However, the PAA exposed fish survived longer than the PES-free controls! This might be due to a disinfection of other pathogens by PAA. In test II, the fish (length 12 cm) were less infected than fish in test I. Four of six fish died in the group exposed with 2 ppm PAA for 24 hours. The abundance of I.-m.-trophonts was determined in mucus, fin and gill tissues of all fish. Significant differences could not be observed between test I and test II because of dissimilar: 1. exposure in time and concentration, 2. age and condition of the fish and 3. homogenity of the variances. Therefore, no therapy strategy was successful while fighting the parasitic trophonts protected by the overlaying fish tissues. We speculate that a successful therapy of I. m. with PAA is, as known e.g. for malachite green, only possible while fighting the free living stages theronts and tomonts. This will be part of our subsequent investigations.     

Campylobacter-induced interleukin-8 responses in human intestinal epithelial cells and primary intestinal chick cells

Campylobacter (C.) jejuni and C. coli can cause gastrointestinal disorders in humans characterized by acute inflammation. Inflammatory signals are initiated during interaction between these pathogens and human intestinal cells, but nothing is known about the stimulation of avian intestinal cells by Campylobacter. Interleukin-8 (IL-8) as a proinflammatory chemokine plays an important role in mobilizing cellular defence mechanism. IL-8 mRNA expression in both human intestinal cells (INT 407) and primary intestinal chick cells (PIC) was determined by quantitative real-time RT-PCR. The secretion of IL-8 protein by INT407 was measured using ELISA. Although C. jejuni and C. coli are considered to be harmless commensals in the gut of birds, the avian Campylobacter isolates investigated were able to induce the proinflammatory IL-8 in PIC as well as in INT407. In an in vitro system, C. jejuni as well as C. coli were able to induce IL-8 mRNA in PIC. Relation between the virulence properties like toxin production, the ability to invade and to survive in Caco-2 cells and the level of IL-8 mRNA produced by INT 407 and PIC after infection with Campylobacter strains was also investigated.     

PRRSV-eradication: an option for pig herds in Germany?

The problem of successfully controling PRRS with traditional methods has led to a growing interest in eradication. This review summarizes the current literature on topics of PRRS-eradication, including the relevant routine diagnostic procedures, routes of virus transmission between pig herds (as i.e. pig movement, semen, aerosols, insects, fomites, transport vehicles) and eradication by close&rollover and test&removal, respectively. On the basis of this knowledge and experiences it can be concluded that PRRS eradication in Germany with its intensive pig production and remarkably high pig density in several regions may only be possible through a national eradication program. The lack of potent marker vaccines that reduce the virus spread significantly, combined with the lack of differentiating diagnostic tests for routine laboratory use leads to the recommendation not to launch a national eradication program under the given circumstances. For the future it should be taken into account that the situation after reintroduction of PRRSV in a free region could only be managed by stamping-out which is generally poorly accepted by the majority of pig producers.     

Brain penetration of emodepside is increased in P‐glycoprotein‐deficient mice and leads to neurotoxicosis

The antiparasitic drug emodepside (EMO) is a substrate of the P‐glycoprotein multidrug efflux carrier (P‐gp; syn. MDR1, ABCB1), which has an important function in protecting the brain from potentially toxic compounds by functional drug efflux at the blood–brain barrier (BBB). Many dogs of the Collie breed and even dogs of many other breeds have a loss‐of‐function 4‐bp deletion mutation in the MDR1 gene. In these dogs, brain penetration of many P‐gp‐transported drugs is increased and so their therapeutic usage is restricted. To elucidate the role of P‐gp at the BBB for the brain penetration of EMO, we applied EMO at 1 mg/kg to mdr1‐deficient (PGP^mut) and mdr1‐intact (PGP^WT) CF1 mice. Whereas in the brain of the PGP^WT mice, EMO was below the detection level of 10 ng/g, its concentration was at 43.7 ng/g in the PGP^mut mice. Furthermore, appearance of neurological toxicity was analyzed in these mice after application of 1 mg/kg EMO using a rotarod setup. In all PGP^mut mice, but not in the PGP^WT mice, the walking performance on the rotarod was impaired by EMO with clear differences in the degree and duration of neurological toxicity. Some of the mice were completely unable to walk on the rotarod already at 2 h after drug application and showed long‐lasting ataxia over >24 h. Others even showed significantly reduced walking performance, but completely recovered within 1 day. In conclusion, P‐gp restricts brain penetration of EMO and prevents neurological toxicity of this drug in mice.