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     

Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.     

Spirochetemia caused by Borrelia turicatae infection in 3 dogs in Texas

Spirochetemia was diagnosed in 2 Siberian Huskies and a Rottweiler from the northwestern region of Texas between June 1999 and October 2001. Clinical findings were nonspecific; tick exposure was documented in 2 of the dogs. Hematologic abnormalities included anemia (n=2), neutrophilia (n=2, including 1 with a left shift), lymphopenia (n=3), eosinopenia (n=3), and thrombocytopenia (n=2). One anemic dog had a positive Coombs' test. In 1 dog, Western blot analysis of serum yielded multiple positive bands with B turicatae lysate, indicating the spirochetemia most likely was due to B turicatae infection. In 2 dogs, spirochetes were cultured from the blood and identified using DNA analysis as Borrelia turicatae; 1 of these dogs also was seropositive for Ehrlichia canis and B burgdorferi. In 2 cases, spirochetemia was more prominent in blood smears prepared immediately after sample collection than in smears prepared from EDTA blood. Two dogs recovered with doxycycline treatment; 1 dog declined clinically despite treatment and was euthanized. B turicatae is the agent of tick-borne (endemic) relapsing fever in humans and is distinct from B burgdorferi, the agent of Lyme disease; however, serologic cross-reactivity may occur. B turicatae is transmitted by the soft tick, Ornithodoros turicata, and infection should be considered in dogs with spirochetemia and possible exposure to the tick vector.     

Signatures of adaptation to obligate biotrophy in the Hyaloperonospora arabidopsidis genome

Many oomycete and fungal plant pathogens are obligate biotrophs, which extract nutrients only from living plant tissue and cannot grow apart from their hosts. Although these pathogens cause substantial crop losses, little is known about the molecular basis or evolution of obligate biotrophy. Here, we report the genome sequence of the oomycete Hyaloperonospora arabidopsidis (Hpa), an obligate biotroph and natural pathogen of Arabidopsis thaliana. In comparison with genomes of related, hemibiotrophic Phytophthora species, the Hpa genome exhibits dramatic reductions in genes encoding (i) RXLR effectors and other secreted pathogenicity proteins, (ii) enzymes for assimilation of inorganic nitrogen and sulfur, and (iii) proteins associated with zoospore formation and motility. These attributes comprise a genomic signature of evolution toward obligate biotrophy.