von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers

OBJECTIVE: To define the relationship between clinical expression of a type-1 von Willebrand disease phenotype and genotype at 2 von Willebrand factor marker loci in Doberman Pinschers. ANIMALS: 102 client-owned Doberman Pinschers. PROCEDURES: Dogs were recruited on the basis of plasma von Willebrand factor concentration, clinical history, and pedigree. Blood samples and response to a history questionnaire were obtained for each dog. Plasma von Willebrand factor concentration was measured by use of an ELISA, and genotyping was performed via polymerase chain reaction for 1 intragenic and 1 extragenic von Willebrand factor marker. Amplification product size was determined by use of polyacrylamide gel electrophoresis (intragenic marker) or automated sequence analysis (extragenic marker). Western blots were prepared from a subset of dogs with low plasma von Willebrand factor concentration to evaluate multimer distribution. RESULTS: Strong associations were detected between plasma von Willebrand factor concentration and von Willebrand factor marker genotype. Twenty-five dogs had substantial reduction in plasma von Willebrand factor concentration and multiple hemorrhagic events. All were homozygous for a 157-base-pair intragenic marker allele and homozygous or compound heterozygous for 1 of 4 extragenic marker alleles. These marker genotypes were exclusively detected in dogs with low plasma von Willebrand factor concentration, although some dogs with these genotypes did not have abnormal bleeding. CONCLUSIONS AND CLINICAL RELEVANCE: Type-1 von Willebrand disease in Doberman Pinschers is associated with the von Willebrand factor gene locus; however, the expression pattern in this breed appears more complex than that of a simple recessive trait.     

Canine leukocyte adhesion deficiency: presence of the Cys36Ser beta-2 integrin mutation in an affected US Irish Setter cross-breed dog and in US Irish Red and White Setters

Canine leukocyte adhesion deficiency (CLAD) is a primary immunodeficiency disease characterized by recurrent bacterial infections in the presence of marked leukocytosis. The disease was 1st described in the mid-1980s in a cross-breed Irish Setter Dog in the United States. It results from a defective beta-2 subunit of heterodimeric leukocyte adhesion proteins. The causative mutation for CLAD in Irish Setter Dogs from Europe has been identified as a missense mutation at base pair position 107 in the beta-2 integrin subunit gene (ITGB2) that results in an amino acid change from cysteine to serine at amino acid 36 (Cys36Ser) in the beta-2 integrin subunit protein. In the current work, the originally described dog with CLAD has been genetically tested and shown to have the same mutation as the European Irish Setters. This suggests that the mutation has been in the Irish Setter population for many generations spanning more than 2 decades. A related breed, the Irish Red and White Setter, has a history of interbreeding with Irish Setters and shares a common ancestry with the Irish Setter breed. DNA from Irish Red and White Setters residing in the United States was screened either by sequencing or by the newly developed restriction enzyme test for the Irish Setter Cys36Ser CLAD mutation. Seven of 54 dogs tested (13%) were found to be carriers of the Irish Setter CLAD mutation. Five of these were directly related to a sire from the UK, demonstrating the importation of an allele from another continent and establishing the need for genetic testing in this breed in the United States.     

The influence of various confounding factors on mechanical nociceptive thresholds in the donkey

ObjectiveTo evaluate a mechanical nociceptive threshold (MNT) testing device in the donkey, and to investigate the influence of potential confounders on MNTs generated.Study designProspective, randomised.AnimalsSixteen castrated male donkeys aged 4–9 years, weighing 105–170 kg.MethodsMechanical nociceptive thresholds were measured using an actuator with three pins placed on the dorsal aspect of the distal limb, connected to a force meter. The pins (surface area 15 mm²) were extruded onto the limb by pressurising an air-filled syringe, until the MNT force (when foot-lift was observed) or 25 N (cut-off force) was reached. Effect on MNT of presence of a companion donkey, the limb tested, rate of application of force, testing location, level of distraction, ambient temperature and hair cover at the test site was evaluated. Long and short-term repeatability of MNT was assessed. Data were analysed using general linear models and Mann–Whitney U tests, p < 0.05 was considered significant.ResultsIncreasing the rate of force application significantly increased the mean ± SD MNT from 9.2 ± 2.0 N when applied at 0.4 N sec^?1 to 10.6 ± 2.1 N when applied at 1.2 N sec^?1 (p = 0.001). No other factors significantly influenced MNT. Mean MNT remained stable over a 3 week period, however MNTs were significantly (p = 0.006) higher (12.8 ± 3.0 N cf 10.3 ± 1.9 N) after a 12 month interval.Conclusions and clinical relevanceWhen designing studies measuring MNT in donkeys, rate of application of force must be standardised. Donkeys’ MNTs have good short-term stability suggesting this technique is appropriate for short-term analgesiometry studies; however variability of MNTs over the long-term is greater.     

Adult-onset cerebellar cortical abiotrophy and retinal degeneration in a domestic shorthair cat.

A 4-year-old, neutered male domestic shorthair cat presented for evaluation of ataxia and visual deficits. Neurological examination revealed severe cerebellar ataxia with symmetrical hypermetria and spasticity, a coarse whole-body tremor, positional vertical nystagmus, and frequent loss of balance. A menace response was absent bilaterally, and the pupils were widely dilated in room light. A funduscopic examination revealed markedly attenuated to absent retinal vessels and pronounced tapetal hyperreflectivity, findings consistent with end-stage retinal degeneration. Blood work evaluation included retroviral testing, a complete blood count, serum biochemistry analysis, taurine levels, and toxoplasma immunoglobulin G and immunoglobulin M titers. All were within reference ranges. The patient was euthanized, and a necropsy was performed. Microscopically, lesions of the nervous system were confined to the cerebellum and were consistent with cerebellar cortical abiotrophy. Selective photoreceptor degeneration was seen on histopathological examination of the retina with a reduction in the number of rods and cones. The combination of clinical findings and histopathological lesions seen here has not been previously reported in the cat.     

The danger model: a renewed sense of self

For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign.     

A study to evaluate buprenorphine at 40 μg kg(-1) compared to 20 μg kg(-1) as a post-operative analgesic in the dog

ObjectiveComparison of the analgesic effect of buprenorphine at 20 or 40 μg kg^?1.Study designAn investigator ‘blinded’, randomised study.AnimalsTwenty six dogs presented for ovariohysterectomy.MethodsDogs were premedicated intramuscularly with acepromazine 0.03 mg kg^?1 and buprenorphine at either 20 (B20, n = 12) or 40 μg kg^?1 (B40, n= 14) followed by anaesthetic induction with propofol and maintenance with isoflurane. During anaesthesia non invasive blood pressure, heart rate, respiratory rate, blood oxygen saturation, inspired and expired volatile agent, end-tidal carbon dioxide and ECG were recorded. Pain and sedation were assessed using interactive VAS scores; mechanical nociceptive thresholds were measured at the wound and hindlimb - all were assessed before and up to 22 hours after administration. Carprofen was used for rescue analgesia.ResultsThere were no significant differences between the two groups for any of the parameters examined. Rescue analgesia was required around 5 hours after administration of buprenorphine in a significant number of animals. Sedation was good preoperatively and scores decreased over time postoperatively. Hock thresholds did not change over time; wound thresholds decreased significantly compared to the baseline value from 3 hours onwards.ConclusionsAdministration of buprenorphine at either 20 or 40 μg kg^?1 IM with acepromazine provided good pre-operative sedation. Cardiovascular and respiratory values remained within clinically acceptable limits during anaesthesia. There was no evidence that increasing dose increased adverse events that may be associated with opioid administration (e.g. bradycardia and respiratory depression).Clinical relevanceIncreasing the dose of buprenorphine from 20 to 40 μg kg^?1 did not provide any benefits with respect to analgesia after ovariohysterectomy as assessed using the VAS scoring system.     

Spinal cord granuloma due to Coccidioides immitis in a cat

A6-year-old 5.5-kg female spayed domestic short-haired cat from Tucson, AZ, presented with an ˜5-day history of progressive pelvic limb weakness. The owners had returned from a weekend away to find the cat unable to use her left pelvic limb. Approximately 2 months previously, the cat had a cough and was treated for presumptive asthma with 5 mg prednisone PO q24h. The cat had a similar cough 1 year previously and seasonal allergy was suspected. The cough resolved and prednisone treatment was discontinued. Other past pertinent history included a skin problem ˜4 years previously that was described as alopecia, erythema, and pruritus of a pelvic limb. This problem had been diagnosed as an allergy and had since resolved. The cat was housed exclusively indoors and had been adopted as a kitten from a local retail store. Viral titers (FeLV and FIV) were negative, and regular vaccinations and veterinary examinations had been completed