Canine leukocyte adhesion deficiency colony for investigation of novel hematopoietic therapies

The genetic immunodeficiency disease canine leukocyte adhesion deficiency (CLAD) was originally described in juvenile Irish Setters with severe, recurrent bacterial infections. CLAD was subsequently shown to result from a mutation in the leukocyte integrin CD18 subunit which prevents leukocyte surface expression of the CD11/CD18 complex. We describe the development of a mixed-breed CLAD colony with clinical features that closely parallel those described in Irish Setters. We demonstrate that the early identification of CLAD heterozygotes and CLAD-affected dogs by a combination of flow cytometry and DNA sequencing allows the CLAD-affected animals to receive life-saving antibiotic therapy. The distinct clinical phenotype in CLAD, the ability to detect CD18 on the leukocyte surface by flow cytometry, and the history of the canine model in marrow transplantation, enable CLAD to serve as an attractive large-animal model for the investigation of novel hematopoietic stem cell and gene therapy strategies.     

Canine leucocyte adhesion deficiency in Irish red and white setters

Seventy-six Irish red and white setter samples were tested for the recently documented CD18 point mutation which manifests as canine leucocyte adhesion deficiency (CLAD) in Irish setters. Six carrier dogs were identified, all originating from a lineage within which sporadic deaths from symptoms consistent with CLAD had been observed. This is the first demonstration that the CLAD mutation exists outside the Irish setter population, confirming that the mutation is present in a significant minority of Irish red and white setters. Routine testing by breeders to identify carrier animals will enable the eradication of CLAD from the Irish red and white setter population.     

Neurologic, endocrinologic, and pathologic findings associated with large pituitary tumors in dogs: eight cases (1976-1984)

Invasive tumors of the pituitary gland were diagnosed in 8 dogs. Seven of the dogs had been treated for pituitary-dependent hyperadrenocorticism before the onset of neurologic signs. All 8 dogs had behavior abnormalities and similar neurologic signs: 6 dogs had rotary nystagmus and 7 dogs had symmetric tetraparesis. Once neurologic signs developed, the clinical course in all 8 dogs had a mean duration of 4.7 +/- 2.0 months before death or euthanasia; 5 dogs had a clinical course of less than or equal to 2 months. Necropsy was performed in 7 dogs. The histologic diagnosis was malignant pituitary adenocarcinoma in 2 dogs and pituitary adenoma in 5 dogs.     

Studies on the association of Aspergillus fumigatus with ocular infections in animals

The occurrence and aetiological significance of Aspergillus fumigatus, an opportunistic pathogen, have been studied in 93 animals with various ophthalmological problems. A total of 93 eye swabs collected from 35 mules, 26 dogs, 13 fowl, 11 cattle, five buffaloes and three camels were investigated mycologically for the presence of A fumigatus. The pathogen was isolated in pure and heavy growth from the swabs from two dogs, one bull, one mule and one fowl. The fungus was also demonstrated directly in clinical material by the potassium hydroxide technique. A fumigatus could not be cultured from the buffaloes and camels. All the five cases had been treated with broad spectrum antibiotics and cortisone and two had received traumatic injury to the eyes (one mule and a bull). The organism was not isolated in pure culture from the conjunctival swabs of 22 apparently healthy animals (11 dogs, six mules, three fowl and two cattle). Many other saprophytic fungi were recovered in mixed cultures but were considered to be contaminants. The clinical signs and diagnostic criteria of oculomycosis have been discussed.     

Combined clotrimazole irrigation and depot therapy for canine nasal aspergillosis

OBJECTIVES: To evaluate the effect of short duration 1 per cent clotrimazole flush when combined with 1 per cent clotrimazole cream instilled into the frontal sinuses for the treatment of nasal aspergillosis in 14 dogs. METHODS: Fourteen dogs with clinical, radiological, serological and rhinoscopic findings consistent with nasal aspergillosis were treated by frontal sinus trephination and a short, five-minute flushing of 1 per cent topical clotrimazole solution followed by a 1 per cent clotrimazole cream instilled as a depot agent. RESULTS: Twelve of the 14 dogs (86 per cent) responded well to treatment and either had no clinical signs after treatment or had signs consistent with mild rhinitis during a minimum follow-up period of six months. Only one dog required multiple treatments. Treatment was well tolerated by all patients, with minimal complications. CLINICAL SIGNIFICANCE: This treatment compares favourably to previously published data using one-hour topical clotrimazole or enilconazole flushing treatment protocols. The treatment technique significantly reduced treatment time under anaesthesia.     

4-Methylpyrazole as treatment for naturally acquired ethylene glycol intoxication in dogs

Eight dogs with ethylene glycol intoxication were treated with 4-methylpyrazole, an alcohol dehydrogenase inhibitor. Dogs had clinical signs referable to ethylene glycol ingestion including ataxia, depression, vomiting, polyuria, and dehydration. Metabolic abnormalities included high anion gap metabolic acidosis, serum hyperosmolality, isosthenuria, and monohydrate and dihydrate calcium oxalate crystalluria. Serum and urine ethylene glycol concentrations were determined to confirm ingestion of ethylene glycol. A 50-mg/ml solution of 4-methylpyrazole in propylene glycol was administered iv as follows: initial treatment, 20 mg/kg of body weight; at 17 hours after admission, 15 mg/kg; at 25 hours after admission, 5 mg/kg. By 24 hours after admission, all dogs had clinical and metabolic improvement. Of the 8 dogs, 7 were released within 3 days of admission. Four of the 8 dogs returned for follow-up evaluation, at which time biochemical or hematologic abnormalities were not observed.     

Canine Ehrlichiosis in Six Dogs with Persistently Increased Antibody Titers

Chronic ehrlichiosis was diagnosed in six dogs on the basis of increased immunofluorescent antibody titers to Ehrlichia canis. Although clinical signs varied, all six dogs were anemic, hyperglobulinemic, and an IgG monoclonal gammopathy was documented in five dogs in which serum protein electrophoreses were performed. All dogs were treated with tetracycline for at least 14 days; four dogs also received immunosuppressive drugs. Clinical signs resolved within 1 week, hematologic abnormalities resolved in 1 to 5 months, and increased globulin concentrations normalized in 1 to 15 months; however, E. canis antibody titers remained increased for 15 to 31 months after initiation of treatment. Results of this study show that increased E. canis titers can persist in dogs with ehrlichiosis for many months after clinical recovery.     

Efficacy of selamectin in the treatment and control of clinical signs of flea allergy dermatitis in dogs and cats experimentally infested with fleas

OBJECTIVE: To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments. DESIGN: Randomized controlled trial. ANIMALS: 22 dogs and 17 cats confirmed to have FAD. PROCEDURE: Animals were housed in carpeted pens capable of supporting the flea life cycle and infested with 100 fleas (Ctenocephalides felis) on days -13 and -2 and on alternate weeks with 10 to 20 fleas. On day 0, 11 dogs and 8 cats were treated with selamectin (6 mg/kg [2.7 mg/lb]). Dogs were retreated on day 30; cats were retreated on days 30 and 60. All animals were examined periodically for clinical signs of FAD. Flea counts were conducted at weekly intervals. RESULTS: Throughout the study, geometric mean flea counts exceeded 100 for control animals and were < or = 11 for selamectin-treated animals. Selamectin-treated cats had significant improvements in the severity of miliary lesions and scaling or crusting on days 42 and 84, compared with conditions on day -8, and in severity of excoriation on day 42. In contrast, control cats did not have any significant improvements in any of the clinical signs of FAD. Selamectin-treated dogs had significant improvements in all clinical signs on days 28 and 61, but in control dogs, severity of clinical signs of FAD was not significantly different from baseline severity at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of selamectin, even without the use of supplementary environmental control measures and with minimal therapeutic intervention, can reduce the severity of clinical signs of FAD in dogs and cats.     

Lumbosacral osteochondrosis: radiological features and surgical management in 34 dogs

Lumbosacral osteochondrosis has been diagnosed with increasing frequency over the past few years. Nevertheless, poor recognition of the condition continues to lead to frequent misdiagnosis. A study was therefore undertaken over a 12-year period (1986 to 1998) to describe the use of a variety of radiological studies to define the syndrome and the use of different surgical techniques for optimal treatment of the condition. Dogs with clinical signs of cauda equina neuropathy and radiological signs of lumbosacral osteochondrosis were older than 14 months (mean age 6.3 years). German shepherd dogs, boxers and rottweilers were heavily represented. Of the 34 dogs with osteochondrosis in this study, the lesion appeared to be related to the sacrum in 31 dogs (91 per cent) and the seventh lumbar vertebra in the remaining three dogs (9 per cent). Twenty-seven male and seven female dogs were affected (4:1). Out of the 34 dogs, six (18 per cent) were treated conservatively and the remaining 28 (82 per cent) were treated surgically. The outcome of surgical treatment was considered to be satisfactory in 24 (86 per cent) of these latter dogs.     

Familial non-rcd1 generalised retinal degeneration in Irish setters

Four Irish setters were diagnosed with bilateral retinal degeneration and cataracts at an age ranging from six to 11 years. In three of these dogs, progressive night blindness was reported from an age of eight to 11 years. In the fourth dog, aged six, no signs of visual impairment had been noticed. In all four dogs, the rod-cone dysplasia type 1 (rcd1) mutation was excluded as a cause, using an allele-specific PCR. From their three-generation pedigrees, a familial relationship was detected in three out of four dogs, which were also related to four additional Irish setter dogs with a history and clinical signs suggestive of late-onset progressive retinal degeneration. These results suggest the existence of a possibly hereditary, late-onset, progressive retinal atrophy in the Irish setter breed, that is distinct from rcd1.     

Leucocyte adhesion protein deficiency in Irish setter dogs.

Investigation of 12 Irish setter puppies from six litters with severe recurrent infections, neutrophilia and low body weight revealed a leucocyte adhesion protein deficiency with a total lack of CD11b and CD18. Their neutrophil function was severely impaired with a totally absent capacity to ingest C3b-opsonized particles, a significantly impaired capacity to ingest IgG-opsonized particles and significantly diminished adherence to nylon wool when compared with neutrophils from healthy control dogs. The chemiluminescence of patient neutrophils activated by C3b-opsonized particles was, consequently, significantly decreased compared with that of control neutrophils, while the respiratory burst assayed by phorbolmyristate acid (PMA) stimulated nitroblue tetrazolium (NBT)-reduction was normal in the patient group. Random migration and chemotactic responses of patient and control neutrophils, were similar. The etiology, pathogenesis and clinical manifestations of the Irish setter leucocyte adhesion deficiency were similar to that of the leucocyte adhesion deficiency in humans.     

Idiopathic detrusor-urethral dyssynergia in dogs: a retrospective analysis of 22 cases

Results of a retrospective study of 22 dogs with signs of dysuria and/or stranguria in which a diagnosis of idiopathic detrusorurethral dyssynergia was made are presented. The diagnosis was based on the exclusion of detectable pathological conditions which could also cause urine outflow obstruction. The affected cases were 22 middle-aged male dogs (mean age 4·9 years) of large and giant breeds (mean bodyweight 36·7 kg). Nine dogs had had periodic clinical signs for longer than one year, one for seven months and eight for two to five weeks, while in four dogs signs had begun four to five days before referral. All dogs received the α-sympatholytic agent prazosin as an initial treatment and in 11 it remained the only therapy. There was a good effect in seven and a moderate response in the other four dogs. In one dog, prazosin was ineffective and was replaced by diazepam, which markedly reduced the signs. Three other dogs required frequent catheterisation and antibiotics were administered. These dogs responded favourably. Another three dogs with evidence of impaired bladder contractility were also treated with the parasympathomimetic agent carbachol. One did not improve and was euthanased. Four dogs developed bladder paralysis and severe infectious cystitis. Only one of these could be managed satisfactorily by long-term administration of prazosin, carbachol and antibiotics, and the others had to be euthanased.     

Clinical and biochemical changes in 53 Swedish dogs bitten by the European adder - Vipera berus

Background

Every year many dogs in Sweden are bitten by Vipera berus, the only venomous viper in Sweden. This prospective study investigated clinical signs, some biochemical parameters, treatment, and progress of disease after snakebite in 53 dogs. Effects of treatment with and without glucocorticoids were evaluated.

Methods

All fifty-three dogs bitten by Vipera berus were examined the same day the dog was bitten and the next day. Two more examinations during 23 days post snake bite were included. Creatinine, creatine kinase (CK), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), alkaline phosphatase (ALP) and bile acid results were followed through 3 to 4 samplings from 34 of the dogs.

Results

All dogs had variable severity of local swelling in the bite area and 73 per cent had affected mental status. Initial cardiac auscultation examination was normal in all dogs, but six dogs had cardiac abnormalities at their second examination, including cardiac arrhythmias and cardiac murmurs. All dogs received fluid therapy, 36 dogs were given analgesics, 22 dogs were treated with glucocorticoids, and ten dogs were treated with antibiotics. Evidence of transient muscle damage (increased CK) was seen one day after the snake bite in 15 (54%) of 28 sampled dogs. Moderate changes in hepatic test results occurred in 1 dog and several dogs (22 of 34) had transient, minor increases in one or more hepatic test result. No dog died during the observation period as a consequence of the snake bite.

Conclusions

Snake bite caused local swelling in all dogs and mental depression of short duration in most dogs. Some dogs had transient clinical signs that could be indicative of cardiac injury and some other had transient biochemical signs of liver injury. Treatment with glucocorticoids did not have any clear positive or negative effect on clinical signs and mortality.     

Hypothyroidism in the dog: a retrospective study of sixteen cases

Sixteen dogs with confirmed hypothyroidism were reviewed. The diagnosis was based on subnormal plasma thyroxine concentration and poor response following TSH administration. Common clinical signs were alopecia (12 dogs), lethargy (11) and obesity (11). Plasma cholesterol concentrations were abnormally high in 10 of 14 cases tested, five of 12 were anaemic and three of five had increased creatine phosphokinase activity. Skin changes compatible with endocrinopathy were present in all five cases biopsied. Spontaneous muscle activity was found on electromyography in four cases so examined. All dogs were treated with sodium levothyroxine, and 10 of 13 for which information was available responded satisfactorily.     

ULTRASONOGRAPHIC DIAGNOSIS OF CANINE HYDROCEPHALUS

The brains of 23 canine patients and six random-source dogs were examined ultrasonographically through the bregmatic fontanelle or a surgical craniotomy. Fifteen dogs had abnormal neurologic signs; the others were normal on neurologic examination. Untrasound results were compared with signalment, clinical signs, electroencephalography, computed tomography, radiology and histopathology. The purposes of the study were to demonstrate the use of ultrasound for the diagnosis of canine hydrocephalus and to determine whether there is a relationship between ventricular size and clinical signs. Lateral ventricles were considered enlarged if lateral ventricular height, ventricle-mantle ratio, or ventricle-hemisphere ratio, at the level of or caudal to the interthalamic adhesion in the transverse plane, exceeded 0.35 cm, 0.25 or 0.19, respectively. Of the 29 dogs examined, 14 had enlarged lateral ventricles and abnormal neurologic signs. Five dogs had enlarged lateral ventricles but appeared neurologically normal (occult hydrocephalus). Correlation was poor between ventricular size and clinical signs.     

Renal amyloidosis in related English foxhounds

Renal amyloidosis was diagnosed in six related English foxhounds from two separate hunting kennels. There was no apparent age or sex predilection. All the dogs had clinical and laboratory findings compatible with renal disease. The onset of clinical signs was acute in all cases with death or euthanasia in five of the six affected dogs occurring within one week of presentation. The remaining dog was treated with diuresis which produced a temporary improvement. Histological examination of renal tissue from affected dogs identified the presence of both glomerular and interstitial amyloid, which was confirmed by immunohistochemical staining to be of the reactive type (amyloid A). There were occasional sclerosed glomeruli or glomeruli with thickened Bowman's capsules, in addition to interstitial and periglomerular infiltration with a predominance of plasma cells and lymphocytes and secondary changes including tubular eosinophilic casts. Renal papillary necrosis was identified in three dogs. One hound had concurrent multicentric lymphoma. Pedigree analysis of the affected dogs revealed that four individuals shared a common great grandsire and that the same dog was the grand-sire of a further case. Pedigree analysis of five additional dogs from one of the kennels, all of which had clinical signs of acute renal failure but from which renal tissue was not available, revealed a close relationship to those foxhounds with confirmed renal amyloidosis.     

Piroxicam, mitoxantrone, and coarse fraction radiotherapy for the treatment of transitional cell carcinoma of the bladder in 10 dogs: a pilot study

Ten dogs with transitional cell carcinoma (TCC) of the bladder were treated with a combination of once-weekly coarse fraction radiation therapy (six weekly fractions of 5.75 Gray [Gy]), mitoxantrone chemotherapy, and piroxicam. All dogs completed the radiation therapy protocol, and only minimal side effects were observed. Only two (22%) dogs achieved a measurable partial response; however, 90% of the dogs had amelioration of their urinary clinical signs. The median survival time for all dogs was 326 days. While this treatment protocol was well tolerated, the response rate and overall survival duration was not superior to reports using mitoxantrone and piroxicam without radiation therapy in dogs with TCC.     

Surgical treatment of adrenocortical tumors: 21 cases (1990-1996)

Twenty-four adrenocortical tumors were surgically removed from 21 dogs. Histopathological examination confirmed 18 carcinomas and six adenomas. Four dogs died in the perioperative period. Fifteen of the 17 dogs that survived the perioperative period had long-term resolution of their clinical signs. Two dogs with incompletely resected tumors were treated with mitotane to control their clinical signs. Overall median Kaplan-Meier life-table survival for dogs with carcinomas was 778 days (range, one to 1,593 days). Median survival for dogs with adenomas was not reached (range, 11 to 730 days). Histopathological diagnosis, histopathological cellular features, age of the dog, and tumor size were not prognostic of outcome.     

Clinical and imaging findings,treatments, and outcomes in 27 dogs with imaging diagnosed trigeminal nerve sheath tumors: A multi‐center study

The clinical behavior of canine trigeminal nerve sheath tumors and benefits of previously reported treatments are incompletely defined. Aims of this retrospective, multicenter, observational study were to describe clinical signs, tumor localization characteristics, treatments, and clinical outcomes in a group of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI) studies, and presentation between 2004 and 2014. A single observer recorded medical record findings and two observers recorded MRI characteristics by consensus. A total of 27 dogs met inclusion criteria (15 treated with stereotactic radiation therapy and 12 unirradiated). Two unirradiated dogs were excluded from outcome analyses. The most common presenting signs were masticatory muscle atrophy (26 dogs), neurologic signs referable to intracranial disease (13), and ocular disease (12). Based on MRI findings, all dogs had disease extending centrally at the level of the brainstem. The most commonly affected trigeminal nerve branches were the mandibular (26 dogs), maxillary (22), and ophthalmic (10). Of 15 dogs treated with stereotactic radiation therapy, one had improved muscle atrophy, and six had poor ocular health after treatment. Neurologic signs improved in 4/5 dogs with intracranial signs. Overall median survival time for the 10 unirradiated dogs with available follow‐up was 12 days and 441 days for the 15 stereotactic radiation therapy dogs. Mean survival times between these groups were not significantly different (mean 95% CI for unirradiated dogs was 44–424 days and mean 95% CI for stereotactic radiation therapy dogs was 260–518 days).