DNA testing for copper toxicosis in Bedlington terriers.
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Alleles↗
Biomedical subjects
M E Herrtage
Publications and source records attributed to M E Herrtage.
Cortisol response to two different doses of intravenous synthetic ACTH (tetracosactrin) in overweight cats.
Fifteen middle-aged to older, overweight cats attending a first-opinion clinic were investigated to rule out hyperadrenocorticism as a cause of their weight problem, using two different protocols for the adrenocorticotropic hormone (ACTH) stimulation test. The cats received intravenous synthetic ACTH (tetracosactrin) at an initial dose of 125 microg; a second test was performed between two and three weeks later, using a dose of 250 microg intravenously. The mean basal serum cortisol concentration was 203 nmol/litre (range 81 to 354 nmol/litre). The highest mean serum cortisol concentration occurred at 60 minutes following the 125 microg dose and at 120 minutes following the 250 microg dose. There was, however, no statistically significant difference between these peak cortisol concentrations attained using either dose of tetracosactrin. A significantly higher mean serum cortisol concentration was attained after the higher dose at the 180 minutes time point, indicating a more prolonged response when compared with the lower dose. The cats were followed up for one year after the initial investigations and none were found to develop hyperadrenocorticism during this time.
Adrenocorticotropic Hormone↗
Primary ciliary dyskinesia in Newfoundland dogs.
Primary ciliary dyskinesia was diagnosed in three Newfoundland dogs with histories of chronic rhinitis and bronchopneumonia from an early age. Thoracic radiographs of two of them showed severe, dependent bronchopneumonia and right displacement of the cardiac apex but normal positioning of other organs. Histopathological examination of sections of lung from the other dog showed severe bronchopneumonia. A semen sample from one dog had a high percentage of spermatozoa with abnormal tails and poor progressive motility. Transmission electron microscopy of nasal brushings from all three dogs showed consistent ultrastructural defects in the cilia, including an absence of outer and inner dynein arms, disorganisation of peripheral doublets, occasional supernumerary doublets and singlets, and consistently disorganised basal bodies and foot processes; sections of trachea from one dog also had disorganised basal bodies. Pedigree analysis was consistent with a monogenic autosomal recessive pattern of inheritance for the defect. One dog is still alive, one dog died aged five years two months, and one dog was euthanased aged nine months. This is the first time primary ciliary dyskinesia has been reported in Newfoundland dogs.
Animals↗
Concurrent central diabetes insipidus and panhypopituitarism in a German shepherd dog.
This report describes a German shepherd dog that was presented with proportionate dwarfism and coat changes typical of hypopituitarism but that was also profoundly polydipsic and polyuric. Investigations established a diagnosis of concurrent central diabetes insipidus. Treatment with desmopressin was successful in managing the polyuria and polydipsia.
Animals↗
Genomic screening for fucosidosis in English Springer Spaniels.
OBJECTIVE: To develop a robust molecular genetic test for alpha-L-fucosidosis in English Springer Spaniels and to screen dogs from the United Kingdom and United States for the mutant allele. ANIMALS: 35 English-bred English Springer Spaniels, 60 American-bred English Springer Spaniels, and 1 affected dog and its parents from a family of English Springer Spaniels in Colorado. PROCEDURE: Polymerase chain reaction analysis was used to amplify the mutated region in the gene encoding alpha-L-fucosidase. High guanine-cytosine (GC) content of the region required use of an amplification buffer with high pH. Mutant and normal alleles were separated by polyacrylamide gel electrophoresis. Molecular genetic test results were compared with enzyme data. RESULTS: A 262-bp PCR product was amplified from normal dogs and compared with a 248-bp product from affected dogs. Carriers had 1 copy of each allele, distinguishable by the 14-bp size difference. Two carriers among the English-bred dogs were identified by use of enzyme and genomic DNA analyses. The molecular defect in dogs from Colorado was proven to be the same as that in British and Australian dogs. None of the other 60 American-bred dogs carried the mutant allele. CONCLUSIONS AND CLINICAL RELEVANCE: A PCR method that can be used to identify dogs affected with or carriers of the autosomal recessive disease fucosidosis was established. Amplification was achieved within a GC-rich region, using a method that may be useful in overcoming amplification problems in GC-rich areas within other genes. Using this test, fucosidosis can be controlled and ultimately eradicated from the English Springer Spaniel population.
Animals↗
Primary ciliary dyskinesia in Newfoundland dogs.
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Animals↗
DNA marker C04107 for copper toxicosis in a population of Bedlington terriers in the United Kingdom.
The DNA microsatellite marker C04107, linked to the Bedlington terrier copper toxicosis locus, is used diagnostically in the USA to detect the disease allele. This marker has been typed in Bedlington terriers of known disease status in the United Kingdom, and it is concluded that it should be useful in eradicating the disease from the breed in the UK. The marker also identified a dog which had been diagnosed on the basis of a liver biopsy as having the disease, as being unaffected; a second liver biopsy confirmed that the dog did not have copper toxicosis.
Animals↗
Medical management of congenital portosystemic shunts in 27 dogs--a retrospective study.
Case records of 27 dogs with medically managed congenital portosystemic shunts were reviewed. Fourteen were followed up by telephone questionnaires to the owners. Age, breed, sex, clinical signs and blood results were similar to previous studies. Weight and quality of life were stable or improved on treatment in all cases. Total serum protein concentration and alanine aminotransferase and alkaline phosphatase activities fell significantly during treatment. Fourteen dogs were euthanased, four were lost to follow-up and nine remained alive. Mean survival time for the dogs euthanased was 9.9 months. Mean follow-up period for the dogs still alive was 56.9 months and all had survived more than 36 months from diagnosis. Surviving dogs with intrahepatic shunts had a significantly shorter follow-up period than dogs with extrahepatic shunts. Two prognostic indicators were identified, age at initial signs and blood urea concentration on presentation, both correlating with survival time. It was demonstrated that a significant proportion of dogs with portosystemic shunts managed medically have a good prognosis.
Animals↗
Hypocortisolaemia in a Labrador retriever.
A four-year-old Labrador retriever was presented with lethargy and exercise intolerance. Clinical examination was unremarkable. A subnormal cortisol response to adrenocorticotrophin hormone (ACTH) was demonstrated (plasma cortisol concentrations before and after administration of ACTH were both below the detection limit of the assay) but plasma aldosterone concentrations were within the normal range. Endogenous plasma ACTH concentrations were high, indicating primary adrenocortical disease. Following glucocorticoid supplementation at a replacement dose (prednisolone 0.1 mg/kg) the dog made a full clinical recovery.
Addison Disease↗
Hyperadrenocorticism in six cats.
The case records of six cats with hyperadrenocorticism presented to the Department of Clinical Veterinary Medicine, University of Cambridge, over an 11-year period were reviewed. Signalment and clinical signs were similar to previous reports but, in contrast to other reports, only three cats had diabetes mellitus on presentation. Abdominal radiographs revealed an adrenal mass in one case, obesity in all cases but no hepatomegaly. The adrenal glands were identified ultrasonographically in three out of six cases. Clinicopathological findings were non-specific. The diabetic cats had a significantly lower serum potassium concentration than the non-diabetic cats (P < 0.05). Results of adrenocorticotrophic hormone (ACTH) stimulation tests were supportive of a diagnosis of hyperadrenocorticism in the five cats in which they were performed. Five cats had pituitary-dependent hyperadrenocorticism (PDH) and one had an adrenal tumour. Differentiation between the two forms of hyperadrenocorticism was possible preoperatively in five out of six cats. Adrenal histopathology confirmed hyperplasia in four cats and adenocarcinoma in one cat. Three cats with PDH underwent bilateral adrenalectomy and two of these cats had low, flat ACTH stimulation tests postoperatively and survived for significant periods. The cat with an adrenal tumour underwent partial unilateral adrenalectomy, maintained a positive ACTH stimulation test postoperatively and was euthanased one week after surgery.
Adrenal Cortex Function Tests↗
Pneumocystis carinii pneumonia in two Cavalier King Charles spaniels.
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Animals↗
Oesophageal injury associated with the administration of an anthelmintic bolus to calves.
Six of 18 calves from a suckler herd which were dosed with a sustained-release anthelmintic bolus, using appropriate equipment, developed clinical signs related to oesophageal perforation. Two died as a direct result of the injuries sustained, one required surgical removal of the paraoesophageal bolus and the remaining three were managed medically. The calves were in the approximate weight range advised by the manufacturers as suitable for dosing, but some were younger than the minimum recommended age. These animals were of a fractious nature having been relatively little handed.
Animals↗
Use of ultrasonography in the diagnosis of tracheal collapse.
Ultrasonographic imaging of the cervical trachea was performed with the neck in both a neutral and a hyperextended position in 10 dogs with tracheal collapse. Tracheoscopy was used to confirm a diagnosis of tracheal collapse. The ultrasound investigation was repeated in 10 dogs of similar size but without tracheal abnormality. The ultrasonographic findings of the affected dogs were compared with those of the normal group and showed an alteration in the shape of the tracheal lumen in the ventrodorsal projection. This study highlights the possibility of identifying changes in the shape of the tracheal lumen during ultrasound investigations as an aid to the diagnosis of tracheal collapse.
Animals↗
Thyroid-stimulating hormone and total thyroxine concentrations in euthyroid, sick euthyroid and hypothyroid dogs.
Canine thyroid-stimulating hormone (cTSH) was measured in a variety of clinical cases (n = 72). The cases were classified as euthyroid, sick euthyroid, hypothyroid or hypothyroid on nonthyroidal therapy on the basis of their history, clinical signs, laboratory results (including total thyroxine concentrations and, where indicated, thyroid-releasing hormone [TRH] stimulation tests) and response to appropriate therapy. Additional samples were taken during some of the TRH stimulation tests to measure the response of cTSH concentrations following TRH administration. A reference range (0 to 0.41 ng/ml) was calculated from the basal concentrations of cTSH in a group of 41 euthyroid dogs. Six of nine cases of confirmed hypothyroidism had basal cTSH concentrations above the reference range, whereas the remainder were within the normal range. One of these three remaining cases was a pituitary dwarf and did not show a rise in cTSH concentration following TRH stimulation. In contrast, only one of a group of six hypothyroid dogs that had been on non-thyroidal treatment within the previous four weeks had increased concentrations of basal cTSH. This study also found that five of a group of 16 dogs with sick euthyroid syndrome had increased cTSH concentrations. It was concluded that cTSH measurements are a useful additional diagnostic test in cases of suspected hypothyroidism in dogs but that dynamic testing is still required to confirm the diagnosis of hypothyroidism.
Animals↗
Role of chronic disseminated intravascular coagulation in a case of canine angiostrongylosis.
A dog whose major clinical signs suggested a coagulopathy, is described. The dog had a history of bleeding episodes and had a severe regenerative anaemia. By using specific factor assays, the coagulopathy was found to be due to a consumptive intravascular process that resembled chronic disseminated intravascular coagulation. Subsequent investigations identified Angiostrongylus vasorum as the cause.
Anemia↗
The molecular defect underlying canine fucosidosis.
Fucosidosis is a lysosomal storage disease which affects humans and English springer spaniel dogs. The disease is recessively inherited in both species and results from a deficiency of the enzyme alpha-L-fucosidase. We have recently cloned and sequenced the canine fucosidase gene (EMBL sequence admission number X92448 (cDNA) and X92671-X92678 (individual exonic data)). The gene spans 12 kb and consists of eight exons. SSCP based mutation analysis of affected animals was carried out on the coding region of this gene both with exonic primers, and intronic primer pairs for each exon. A 14 base pair deletion of the cDNA was identified at the 3' end of exon 1 in fucosidosis affected animals. Surprisingly, PCR based genomic cloning of DNA from these animals showed an identical deletion in this DNA, ending at the start of intron 1. This change causes a frameshift and, in consequence, 25 novel codons are transcribed in exon 2 before the first of two adjacent premature stop codons is encountered.
Animals↗
Use of ACTH stimulation tests to monitor the treatment of canine hyperadrenocorticism.
The case histories of 60 dogs with hyperadrenocorticism were reviewed. Fifty-four of the dogs were treated with mitotane at a mean daily dose rate of 48.8 mg/kg (range 25.6 to 84 mg/kg) for between four and 21 days. The mean weekly maintenance dose of mitotane was 48.8 mg/kg. An adrenocorticotrophic hormone (ACTH) stimulation test was performed before the treatment began, and in 30 cases at the end of the induction course, and the response to ACTH was measured at regular intervals thereafter. Nine of the treated dogs developed complete hypoadrenocorticism during treatment and required permanent mineralocorticoid replacement therapy. Twelve of the dogs had normal responses to an ACTH stimulation test before treatment, and the diagnosis of hyperadrenocorticism was based on the result of a low-dose dexamethasone suppression test. These 12 dogs had consistently lower cortisol levels before and after stimulation with ACTH and four of them developed complete hypoadrenocorticism. In general the clinical signs were well controlled when the cortisol levels were less than 105 nmol/litre before and after the stimulation test. Dogs in which the clinical signs recurred had cortisol levels between 210 and 580 nmol/litre after the test, a level which is within the normal pretreatment range. Twenty-seven of the treated dogs died and six of these deaths were attributable directly to the disease or therapy. The median survival time of the 54 treated dogs was 30 months; eight dogs died during the first 16 weeks of treatment, and the dogs which survived this period had a median survival time of 39 months (mean 50 months).
Adrenal Cortex Function Tests↗
Intracranial haemorrhage in a dobermann puppy with von Willebrand's disease.
Neurological examination of a lethargic, ataxic 12-week-old dobermann revealed decreased conscious proprioception in all its limbs. Haematological examination revealed a low platelet count. Cytological examination of a sample of cerebrospinal fluid revealed evidence of haemorrhage and chronic inflammation. The levels of von Willebrand's factor antigen were extremely low. Skull radiographs were consistent with mild hydrocephalus. Treatment resulted in little clinical improvement and the animal was euthanased. Post mortem examination of the brain revealed an internal hydrocephalus with haemorrhage into the ventricles. It was considered that the animal had suffered severe intracranial haemorrhage as a result of its low level of von Willebrand's factor antigen and that the bleeding may have been potentiated by the low platelet count.
Animals↗