Lower urinary tract pathogens in the dog and their sensitivity to chemotherapeutic agents.

Ninety-six urine samples were collected by a sterile technique from 75 dogs affected with urinary tract disease (cystitis, urolithiasis, prostatitis, etc) involving bacteruria. The infecting organisms were isolated and tested against sensitivity discs (penicillin G, streptomycin, chloramphenicol, tetracycline, sulphamethoxazole/trimethaprin and Sulphatriad). The commonest isolate was Escherichia coli, which was generally sensitive to several agents, though in eight cases it was resistant to all drugs. Next in order were Streptococcus faecalis, Staphylococcus epidermidis and Proteus spp. A double infection was present in 11 cases. Further data give a breakdown for sex and the clinical diagnosis, neither of which was related to any particular organism.     

Hematologic changes associated with Adderall toxicity in a dog

A 1-year-old intact male Boxer was presented to the Texas Veterinary Medical Center for emergency treatment following suspected ingestion of a large number of tablets of Adderall, a pharmaceutical amphetamine. The dog had a temperature of 41.7 degrees C, heart rate of 192 beats per minute, and a respiratory rate of 100 breaths per minute. The dog was anxious and agitated with bilaterally dilated pupils, and shortly thereafter became recumbent and incontinent. Initial CBC results included mild leukopenia and mild thrombocytopenia. The dog was not anemic (HCT 39.9%) and had only slight polychromasia, but had 48 nucleated RBCs/100 WBC (7500/microL). Moderate numbers of neutrophils had hypersegmented nuclei and several pyknotic cells were noted. The metarubricytosis persisted for approximately 56 hours while hypersegmentation and pyknotic cells were no longer found at 8 hours after presentation. The dog received supportive care and recovered uneventfully. We hypothesized that hyperpyrexia associated with Adderall toxicity resulted in inappropriate metarubricytosis due to damaged bone marrow endothelium, and resulted in hypersegmentation and pyknosis due to damaged or accelerated aging of neutrophils in peripheral blood. Metarubricytosis has been reported previously in dogs with heat-induced illness, such as heat stroke.     

Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of collies from France

A study was performed to determine the frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample of collies living in France. Buccal swab samples were collected from approximately 83 collies for determination of MDR1 genotype. DNA was extracted and the polymerase chain reaction was performed to amplify a 148 bp (wildtype MDR1 genotype) or 144 bp (mutant MDR1 genotype) amplicon containing the MDR1 mutation. Sequence analysis was performed to determine the genotype of each dog. Adequate quantities of DNA for unequivocal genotyping were obtained from only 25 of 83 swabs. Twenty percent (5/25) of the collies studied were homozygous for the normal allele (normal), 32% (8/25) were heterozygous (carrier), and 48% (12/25) were homozygous for the mutant allele (affected). The results of this study indicate that a high percentage of collies presenting to veterinarians in France harbor the MDR1 mutation, thus impacting some therapeutic decisions.     

Idiosyncratic toxicity associated with potentiated sulfonamides in the dog

Idiosyncratic toxicity to potentiated sulfonamides occurs in both humans and dogs, with considerable clinical similarities. The syndrome in dogs can consist of fever, arthropathy, blood dyscrasias (neutropenia, thrombocytopenia, or hemolytic anemia), hepatopathy consisting of cholestasis or necrosis, skin eruptions, uveitis, or keratoconjunctivitis sicca. Other manifestations seen less commonly include protein-losing nephropathy, meningitis, pancreatitis, pneumonitis, or facial nerve palsy. The pathogenesis of these reactions is not completely understood, but may be due to a T-cell-mediated response to proteins haptenated by oxidative sulfonamide metabolites. Our laboratory is working on tests to characterize dogs with possible idiosyncratic sulfonamide reactions, to include ELISA for anti-drug antibodies, immunoblotting for antibodies directed against liver proteins, flow cytometry for drug-dependent anti-platelet antibodies, and in vitro cytotoxicity assays. The management of idiosyncratic sulfonamide toxicity involves client education to identify clinical signs early and allow rapid drug discontinuation, supportive care to include possibly ascorbate and glutathione precursors, and avoidance of subsequent re-exposure. It is important to realize that only antimicrobial sulfonamides, such as sulfamethoxazole, sulfadiazine, and sulfadimethoxine, share this clinical syndrome. There is no evidence for cross-reactivity with drugs that have different underlying structures but share a sulfonamide moiety, such as acetazolamide, furosemide, glipizide, or hydrochlorthiazide.     

Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of herding breed dogs living in Australia

A study was performed to determine the frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample of Collies and other herding breeds living in Australia. Buccal swab samples were collected from 33 Collies, 17 Australian Shepherds, 7 Border Collies and 7 Shelties for determination of MDR1 genotype. DNA was extracted and the polymerase chain reaction was performed to amplify a 148 base pair (wildtype MDR1 genotype or 144 base pair (mutant MDR1 genotype) amplicon containing the MDR1 mutation. Sequence analysis was performed to determine the genotype of each dog. Adequate quantities of DNA for unequivocal genotyping were obtained from 61 of 64 samples. The previously described MDR1 mutation was identified in Collies, Australian Shepherds and Shelties living in Australia, but not in Border Collies (although sample numbers were low). Twelve percent (4/33) of the Collies studied were homozygous for the normal allele (normal), 64% (21/33) were heterozygous (carrier) and 24% (8/33) were homozygous for the mutant allele (affected). Results of this study indicate that a high percentage of herding breeds presenting to veterinarians in Australia harbor the MDR1 mutation, thus impacting some therapeutic decisions.     

Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany

MDR1 (ABCB1) P-glycoprotein exerts a protective function in the blood–brain barrier thereby limiting the entry of many drugs and other xenobiotics to the central nervous system. A nonsense mutation has been described for Collies and related dog breeds which abolishes this function and is associated with increased susceptibility to neurotoxic side effects of several drugs including ivermectin, moxidectin and loperamide. In order to evaluate the occurrence and frequency of this nt230 (del4) MDR1 mutation in Germany, we screened 1500 dogs. Frequency of the homozygous mutated genotype was highest for Collies (33.0%), followed by Australian Shepherd (6.9%) and Shetland Sheepdog (5.7%). Thirty-seven percent of the Wäller dogs and 12.5% of the Old English Sheepdogs were heterozygous for the mutant MDR1 (−) allele. Considering the predominant role of MDR1 P-glycoprotein in drug disposition and in particular for blood–brain barrier protection, MDR1 genotype-based breeding programs are recommended for improving the safety of drug therapy in these canine breeds.     

Investigations of toxicity episodes involving chemotherapeutic agents in Victorian poultry and pigeons

This series of case reports details observations on toxicity episodes in poultry due to a variety of chemotherapeutic agents. These problems arose owing to overdosage, variation in species susceptibility, potentiation of the toxic effects of one substance by the presence of another substance, and particular disease or other on-farm factors. Ignorance and accident were responsible for some of these situations. The episodes involved monensin, salinomycin, nicarbazin, sulphaquinoxaline, dinitolmide, dimetridazole, nitrofurans, streptomycin, and 3-nitro-4-hydroxyphenylarsonic acid.     

A novel mutation of the CLCN1 gene associated with myotonia hereditaria in an Australian cattle dog

BACKGROUND: Heritable myotonia is a genetic muscle disorder characterized by slow relaxation of skeletal muscles. The main clinical signs are skeletal muscle stiffness, especially after vigorous contraction, and muscle hypertrophy. Muscle stiffness may be enhanced by inactivity, and often is relieved by exercise. Myotonia can be inherited in an autosomal dominant or recessive manner (Thomsen- or Becker-type myotonia, respectively). In mice, goats, Miniature Schnauzer dogs, and most affected humans, the disorder is caused by mutations in CLCN1, which encodes the skeletal muscle voltage-gated chloride channel, Cl1C-1. HYPOTHESIS: We hypothesized that an Australian Cattle Dog with generalized muscle stiffness and hypertrophy examined at the Ontario Veterinary College would have a mutation in the CLCN1 gene. ANIMALS: A pure-bred Australian Cattle Dog from Ontario, Canada, was used. METHODS: Based on clinical signs and electromyographic test results, a diagnosis of myotonia hereditaria was made, and a muscle biopsy was collected for genetic analysis. RESULTS: Sequence data obtained from the affected dog confirmed that it was homozygous for a single base insertion in the CLCN1 coding sequence. This mutation would result in a truncated ClC-1 protein being expressed, which, based on molecular evidence from other studies, would result in functionally compromised chloride conduction in the skeletal muscles of the animal. CONCLUSIONS AND CLINICAL IMPORTANCE: To the authors' knowledge, this report describes the Ist case of myotonia in an Australian Cattle Dog and represents the 1st non-Schnauzer canine myotonia to be genetically characterized. In addition, we developed a polymerase chain reaction-based genetic screen to detect heterozygotes with this mutation in the at-large Australian Cattle Dog population.     

Haplotype analysis of the MDR1 flanking region in the dog breed Elo

A deletion mutation in the canine multidrug resistance (MDR1) gene provokes drug sensitivity in several dog breeds from the Collie lineage. A haplotype of four microsatellites containing this mdr1-1Delta mutation was conserved among affected breeds. In this study, we analysed the haplotypes of the MDR1 flanking region of 177 dogs of the breed Elo which is composed of several dog breeds including the Old English sheepdog from the Collie lineage. We detected a haplotype in the Elo breed which had previously been associated with the mutant mdr1-1Delta allele in Old English sheepdogs. Using a regression analysis for the probability of the haplotype on the proportion of genes of the founder breeds, we could exclude the Old English sheepdog as origin of this haplotype for the Elo breed. The MDR1 flanking region could be traced back to the Japanese Spitz as one of the founder dog breeds of the Elo and thus, the introgression of the mdr1-1Delta mutation into the dog breed Elo through the Collie lineage is very unlikely.     

Loperamide‐induced expression of immune and inflammatory genes in Collies associated with ivermectin sensitivity

This study evaluated the impact of the ABCB1‐1Δ mutation in Collies which exhibited toxicity toward ivermectin, on changes in gene expression when given the unrelated ABCB1 substrate loperamide, to identify potential biomarkers predictive of drug safety. Thirty‐two healthy intact Collies consisting of dogs with either a wild‐type, heterozygous mutant, or homozygous mutant genotype were used. Whole blood samples were collected from Collies at 0 or 5 h following administration of loperamide at a dose of 0.10 mg/kg. Whole‐genome gene expression microarray was conducted to examine for changes in gene expression. Microarray analysis identified loperamide‐induced changes in gene expression which were specifically associated with ivermectin‐sensitive phenotypes in Collies possessing the ABCB1‐1Δ mutation. Gene pathway analysis further demonstrated that the altered genes are involved in immunological disease, cell death and survival, and cellular development. Thirteen genes, including CCL8 and IL‐8, were identified. Collie dogs harboring ABCB1‐1Δ mutation which also exhibited toxicity toward ivermectin demonstrated systematic responses following loperamide treatment exhibited by altered expression of genes involved in immune and inflammatory signaling pathways. Genes such as CCL8 and IL‐8 are potential biomarkers in whole blood that may predict the safety of loperamide in dogs with ABCB1‐1? mutation associated with ivermectin sensitivity.     

Placentitis associated with leishmaniasis in a dog

A 1.5-year-old Coonhound from Maryland aborted 7 fetuses. Placenta and internal tissues of 1 fetus were examined histologically. The predominant lesion was placentitis characterized by necrosis and infiltration of mixed leukocytes. Numerous Leishmania spp amastigotes were identified in placental trophoblasts, and the diagnosis was confirmed by use of immunohistochemical staining with Leishmania-specific antibodies. Protozoa were not found in the fetal tissues. An indirect fluorescent antibody test yielded a serum titer of 1:100, and a recombinant K39 immunoassay of serum yielded positive results for the K39 Leishmania antigen.     

Chylothorax associated with blastomycosis in a dog

Respiratory distress caused by pleural effusion resulted from chylothorax. Thoracic drainage and lowfat dietary therapy was effective in removing and preventing significant recurrence of the chylothorax; however, the patient died unexpectedly. At necropsy a blastomycotic granuloma found at the precava was considered the cause of the chylothorax. There had been no recognizable antemortem signs of blastomycosis. Blastomycosis can be considered as a rare cause of chylothorax.     

Dermatitis associated with the use of primidone in a dog

A 9-year-old female dog with progressive pruritic dermatitis was examined 9 months after primidone treatment had been initiated. Alopecia, scaling, ulceration, pigmentation, and fissuring were evident over the dorsal trunk, head, perineum, caudal aspect of the thighs, hocks, elbows, and paws. Hydropic degeneration of epidermal basal cells, mononuclear lichenoid infiltrate in the superficial dermis, and marked parakeratotic hyperkeratosis were evident on biopsy. Antinuclear antibody in the serum was not detected and specific patterns of immunoglobulin deposition in the epidermis or basement membrane zone were lacking. Primidone-induced dermatitis was presumptively diagnosed. Successful treatment involved withdrawal of the primidone and administration of corticosteroids and antibiotics to relieve the pruritus and to eliminate the secondary pyoderma.     

Electroretinographic changes after intravenous lipid emulsion therapy in a dog and a foal with ivermectin toxicosis

This case report describes ivermectin‐induced blindness in a dog and a foal with normal ophthalmic fundic examinations and attenuated electroretinography (ERG). Subsequent recovery in ERG was noted following intravenous lipid emulsion (ILE) therapy. A dog and a foal were evaluated for ivermectin‐induced blindness. Clinical signs included dull mentation, absent pupillary light reflexes (PLRs), and absent menace on presentation. The animals had normal fundoscopic examinations; however, in both cases ERG was consistent with neurosensory retinal dysfunction. Following ILE therapy for ivermectin toxicosis, return of menace, PLRs, and normal mentation were noted, as was improvement in ERG and serum ivermectin levels. These are the first documented cases of ivermectin‐induced blindness in a dog and a foal with normal fundic examinations and attenuated ERG. ERG improved in both animals after ILE therapy. ERG may assist in the diagnosis of ivermectin toxicosis in dogs and horses. ILE therapy may hasten recovery in treatment of ivermectin‐induced blindness.