Retrospective assessment of tolerability and efficacy of zoledronate in the palliative treatment of cancer-bearing dogs

Zoledronate is a bisphosphonate frequently used for the treatment of hypercalcaemia of malignancy and tumour-associated bone pain in dogs, however, there is a paucity of information regarding its use in veterinary medicine. The aim of this retrospective study was to report the tolerability of zoledronate in the palliative treatment of cancer-bearing dogs and secondarily to to assess the efficacy of zoledronate for the treatment of hypercalcaemia of malignancy. Thirty-seven dogs (22 with tumour-associated bone pain and 15 with hypercalcaemia of malignancy) that received 114 zoledronate infusions were included. Tolerability was assessed by the absence of post-zoledronate hypocalcaemia or other adverse events as defined by Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events criteria. Efficacy was assessed by comparison of available ionized calcium levels before and after zoledronate administration in hypercalcaemic dogs. In 79% of zoledronate infusions, no adverse events were reported. The majority of adverse events which occurred in the other 21% of infusions could be attributed to concurrent chemotherapy or the underlying neoplastic disease. There was a small but significant increase in creatinine following treatment with zoledronate, however, none of the dogs developed clinically significant renal disease. In eight hypercalcaemic dogs with available ionized calcium following zoledronate administration, ionized calcium decreased rapidly within 7 days following treatment with zoledronate. Zoledronate is well-tolerated with few recorded adverse events, however, monitoring of serum creatinine is advised. Zoledronate seems to be effective in the treatment of hypercalcaemia of malignancy.     

Effect of the route of administration on the mucosal and systemic immune responses to Lawsonia intracellularis vaccine in pigs

In an on‐farm study, 40 weaned piglets aged 3 weeks were vaccinated with Lawsonia intracellularis vaccine orally, IM or IP while a fourth group remained unvaccinated. All vaccinated animals showed increased serum levels of L. intracellularis‐specific IgG antibodies, but significantly elevated concentrations of specific IgG, IgA and cytokines were generated in ileal mucosal secretions from the orally and IP vaccinated pigs when examined at 17 days after vaccination.     

ACVIM Consensus Statement on Therapeutic Antimicrobial Use in Animals and Antimicrobial Resistance

The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.     

Effect of Chronic Administration of Phenobarbital,or Bromide,on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy

Background

Levetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.

Hypothesis/Objectives

To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.

Animals

Eighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).

Methods

Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.

Results

Compared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (C _max) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).

Conclusions and Clinical Importance

Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.     

Effect of Initial GnRH and Duration of Progesterone Insert Treatment on the Fertility of Lactating Dairy Cows

The study compared response to prostaglandin F2α (PG), synchrony of ovulation and pregnancy per AI (P/AI) in a 5‐ vs a 7‐day Ovsynch + PRID protocol and investigated whether the initial GnRH affects P/AI in lactating dairy cows. Two hundred and seventy‐six cows (500 inseminations) were assigned to one of four timed‐AI (TAI) protocols: (i) PRID‐7G; 100 μg GnRH im, and a progesterone‐releasing intravaginal device (PRID) for 7 days. At PRID removal, PG (500 μg of cloprostenol) was given im. Cows received the second GnRH treatment at 60 h after PRID removal and TAI 12 h later. (ii) PRID‐5G; as PRID‐7G except the duration of PRID, treatment was 5 days and PG was given twice (12 h apart). (iii) PRID‐7NoG; as PRID‐7G except the initial GnRH, treatment was omitted. (iv) PRID‐5NoG; as PRID‐7NoG except the duration of PRID, treatment was 5 days. Response to treatments and pregnancy status at 32 and 60 days after TAI was determined by ultrasonography. The percentage of cows ovulating before TAI was greatest in PRID‐7G (17.1%), and the percentage of cows that did not have luteal regression was greatest in PRID‐5G (9.5%). The overall P/AI at 32 and 60 days did not differ among TAI protocols. However, during resynchronization, cows subjected to the 5‐day protocols had greater (p < 0.05) P/AI (45.3% vs 33.6%) than cows subjected to the 7‐day protocols. Pregnancy loss between 32 and 60 days tended (p = 0.10) to be greater in cows that did not receive initial GnRH (14.8%) compared to those that received GnRH (8.2%). In conclusion, the PRID‐5G protocol resulted in fewer cows responding to PG, but P/AI did not differ among TAI protocols. A 5‐day protocol resulted in more P/AI in resynchronized cows, and cows that did not receive initial GnRH tended to experience more pregnancy losses.     

Are the Australian poultry industries vulnerable to large outbreaks of highly pathogenic avian influenza?

Objective   To describe the structure of the Australian poultry industry and discuss the potential for highly pathogenic avian influenza (HPAI) to spread between Australian poultry farms.
Procedure   High densities of poultry farms, frequent contacts between farms by service providers, the supply of live poultry markets (LPM) and the presence of free-range duck flocks in affected regions have been identified as risk factors for the spread of HPAI between flocks in outbreaks causing the death or destruction of over 1 million poultry overseas. Data on 1,594 commercial Australian chicken meat, chicken egg, duck and turkey farms were collected by a telephone questionnaire of farm managers to assess the risk of a HPAI outbreak in Australia.
Results and Discussion   Five regions of Australia had farm densities comparable to overseas regions that experienced widespread HPAI. Common service providers routinely contacted different classes and types of farms over wide geographic areas. However, no responding farms supplied LPM and the majority of duck farms did not produce free-range ducks.
Conclusion   Outbreaks of HPAI have the potential to cause serious impacts on the Australian poultry industry. The risk posted by LPM and free-range ducks is limited, but the movement of genetic stock and common service providers could spread infection between companies, industries or geographical regions. Biosecurity measures are therefore considered critical to limit the secondary spread of infection should an outbreak occur.     

What is your diagnosis? Marked hyperchloremia in a dog

Abstract: A 5‐year‐old neutered male Cavalier King Charles Spaniel was evaluated for a 3‐week history of progressive paresis. The dog had been receiving potassium citrate capsules to acidify urine for the past 2 years because of an earlier history of urolithiasis. Results of neurologic examination, spinal cord radiography, and magnetic resonance imaging of the skull and spinal cord revealed no lesions that could have accounted for the neurologic signs. The main abnormalities on a clinical chemistry profile were marked hyperchloremia (179 mmol/L, reference interval 108–122 mmol/L) and an anion gap of ?50.4 mmol/L (reference interval 16.3–28.6 mmol/L). Because of the severe hyperchloremia, serum bromide concentration was measured (400 mg/dL; toxic concentration >150 mg/dL; some dogs may tolerate up to 300 mg/dL). Analysis of the potassium citrate capsules, which had been compounded at a local pharmacy, yielded a mean bromide concentration of 239 mg/capsule. Administration of the capsules was discontinued and there was rapid resolution of the dog's neurologic signs. This case of extreme bromide toxicity, which apparently resulted from inadvertent use of bromide instead of citrate at the pharmacy, illustrates the importance of knowing common interferents with analyte methodologies and of pursing logical additional diagnostic tests based on clinical and laboratory evidence, even when a patient's history appears to rule out a potential etiology.     

Monitoring distances travelled by horses using GPS tracking collars

Objective The aims of this work were to (1) develop a low-cost equine movement tracking collar based on readily available components, (2) conduct preliminary studies assessing the effects of both paddock size and internal fence design on the movements of domestic horses, with and without foals at foot, and (3) describe distances moved by mares and their foals. Additional monitoring of free-ranging feral horses was conducted to allow preliminary comparisons with the movement of confined domestic horses. Procedures A lightweight global positioning system (GPS) data logger modified from a personal/vehicle tracker and mounted on a collar was used to monitor the movement of domestic horses in a range of paddock sizes and internal fence designs for 6.5-day periods. Results In the paddocks used (0.8–16 ha), groups of domestic horses exhibited a logarithmic response in mean daily distance travelled as a function of increasing paddock size, tending asymptotically towards approximately 7.5 km/day. The distance moved by newborn foals was similar to their dams, with total distance travelled also dependent on paddock size. Without altering available paddock area, paddock design, with the exception of a spiral design, did not significantly affect mean daily distance travelled. Feral horses (17.9 km/day) travelled substantially greater mean daily distances than domestic horses (7.2 km/day in 16-ha paddock), even when allowing for larger paddock size. Conclusions Horses kept in stables or small yards and paddocks are quite sedentary in comparison with their feral relatives. For a given paddock area, most designs did not significantly affect mean daily distance travelled.     

Drugs and the liver

The authors discuss the liver's influence on drug disposition in the body and the influence of drugs on the liver. Drug-induced hepatotoxicity with regard to mechanisms and causative agents is discussed, as well as administration of drugs to patients with existing liver disease.