Hester McAllister

Pravastatin Reduces Marfan Aortic Dilation

Background— The sequelae of aortic root dilation are the lethal consequences of Marfan syndrome. The root dilation is attributable to an imbalance between deposition of matrix elements and metalloproteinases in the aortic medial layer as a result of excessive transforming growth factor-beta signaling. This study examined the efficacy and mechanism of statins in attenuating aortic root dilation in Marfan syndrome and compared effects to the other main proposed preventative agent, losartan. Methods and Results— Marfan mice heterozygous for a mutant allele encoding a cysteine substitution in fibrillin-1 (C1039G) were treated daily from 6 weeks old with pravastatin 0.5g/L or losartan 0.6 g/L. The end points of aortic root diameter (n=25), aortic thickness, and architecture (n=10), elastin volume (n=5), dp/dtmax (maximal rate of change of pressure) (cardiac catheter; n=20), and ultrastructural analysis with stereology (electron microscopy; n=5) were examined. The aortic root diameters of untreated Marfan mice were significantly increased in comparison to normal mice (0.161±0.001 cm vs 0.252±0.004 cm; P<0.01). Pravastatin (0.22±0.003 cm; P<0.01) and losartan (0.221±0.004 cm; P<0.01) produced a significant reduction in aortic root dilation. Both drugs also preserved elastin volume within the medial layer (pravastatin 0.23±0.02 and losartan 0.29±0.03 vs untreated Marfan 0.19±0.02; P=0.01; normal mice 0.27±0.02). Ultrastructural analysis showed a reduction of rough endoplasmic reticulum in smooth muscle cells with pravastatin (0.022±0.004) and losartan (0.013±0.001) compared to untreated Marfan mice (0.035±0.004; P<0.01). Conclusions— Statins are similar to losartan in attenuating aortic root dilation in a mouse model of Marfan syndrome. They appear to act through reducing the excessive protein manufacture by vascular smooth muscle cells, which occurs in the Marfan aorta. As a drug that is relatively well-tolerated for long-term use, it may be useful clinically.

Muscular dystrophy with truncated dystrophin in a family of Japanese Spitz dogs

Muscular dystrophy was diagnosed in seven male Japanese Spitz dogs with clinical signs of slowly progressive exercise intolerance, generalized weakness, myalgia, difficulty chewing and dysphagia. Serum creatine kinase (CK) concentrations were markedly elevated. Histopathology showed degeneration and regeneration of muscle, consistent with a dystrophic phenotype. Immunohistochemical staining for dystrophin and related proteins showed no staining with a monoclonal antibody against the rod domain of dystrophin but near-normal staining with an antibody against the C terminus. Immunoblot analysis in two affected dogs showed a truncated dystrophin protein of approximately 70-80 kDa. The severity of disease showed that this fragment was not large enough to protect from the dystrophic process.

Clinical signs, diagnosis and treatment of three dogs with angiostrongylosis in Ireland

Infection with Angiostrongylus vasorum was diagnosed at necropsy on a dog that died from acute pulmonary haemorrhage, and on recovery of L1 larvae by Baermann examination of faeces from two dogs, one of which had abdominal pain and retroperitoneal haemorrhage, while the other had right-sided heart failure due to cor pulmonale. The presenting signs included syncope (one dog), exercise intolerance (two dogs), cough (two dogs), abdominal pain (one dog) and depression (one dog). One-stage prothrombin time and activated partial thromboplastin time were prolonged in two dogs, buccal mucosal bleeding time was prolonged in one dog and globulin was elevated in all three dogs. Two dogs were treated with fenbendazole and recovered.

Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumour suppression

AIMS The use of doxorubicin (DOX) as a chemotherapeutic agent is limited by cardiac injury. Iloprost, a stable synthetic analogue of prostacyclin, has previously been shown to protect against DOX-induced cardiomyocyte injury in vitro. Here, we addressed whether iloprost is cardioprotective in vivo and whether it compromises the anti-tumour efficacy of DOX. METHODS AND RESULTS Lewis Lung Carcinoma cells were implanted subcutaneously in the flank of C57BL/6 mice. DOX treatment was commenced from when tumours became visible. Iloprost was administered from prior to DOX treatment until sacrifice. Echocardiography and invasive haemodynamic measurements were performed immediately before sacrifice. As expected, DOX induced cardiac cell apoptosis and cardiac dysfunction, both of which were attenuated by iloprost. Also, iloprost alone had no effect on tumor growth and indeed, did not alter the DOX-induced suppression of this growth. CONCLUSION In a murine model, iloprost attenuated the acute cardiac injury and dysfunction induced by DOX therapy without compromising its chemotherapeutic effect.

Cervico-thoracic vertebral osteomyelitis in 14 calves

Fourteen cases of cervico-thoracic (C-T) vertebral osteomyelitis in calves were investigated over a 6 year period. The onset of clinical signs was between 2 and 9 weeks of age. There was no breed or sex predisposition. The clinical history prior to referral extended from 5 days to 8 weeks (mean 20 days). The most common clinical presentation was difficulty in rising with a tendency to knuckle or kneel on the forelimbs which displayed hypotonia and hyporeflexia. In over half the cases pain could be elicited on manipulation of the neck. The lesion in all cases involved one or more of the vertebrae from C6 to T1. The diagnosis was confirmed by radiology and/or at post mortem. Four animals were discharged after treatment, 10 animals were humanely destroyed. Salmonella dublin was isolated from the vertebral lesion in eight of the 10 calves at post mortem.

Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs

OBJECTIVE To assess the value of thyroid scintigraphy to determine thyroid status in dogs with hypothyroidism and various non-thyroidal illnesses. METHODS Thyroid hormone concentrations were measured and quantitative thyroid scintigraphy performed in 21 dogs with clinical and/or clinicopathological features consistent with hypothyroidism. RESULTS In 14 dogs with technetium thyroidal uptake values consistent with euthyroidism, further investigations supported non-thyroidal illness. In five dogs with technetium thyroidal uptake values within the hypothyroid range, primary hypothyroidism was confirmed as the only disease in four. The remaining dog had pituitary-dependent hyperadrenocorticism. Two dogs had technetium thyroidal uptake values in the non-diagnostic range. One dog had iodothyronine concentrations indicative of euthyroidism. In the other, a dog receiving glucocorticoid therapy, all iodothyronine concentrations were decreased. Markedly asymmetric technetium thyroidal uptake was present in two dogs. All iodothyronine concentrations were within reference interval but canine thyroid stimulating hormone concentration was elevated in one. Non-thyroidal illness was identified in both cases. CLINICAL SIGNIFICANCE In dogs, technetium thyroidal uptake is a useful test to determine thyroid function. However, values may be non-diagnostic, asymmetric uptake can occur and excess glucocorticoids may variably suppress technetium thyroidal uptake and/or thyroid hormone concentrations. Further studies are necessary to evaluate quantitative thyroid scintigraphy as a gold standard method for determining canine thyroid function.

Fractures of the cervical vertebral odontoid in four horses and one pony

Four horses and one pony, ranging in age from one to 11 years, were diagnosed with two different types of odontoid peg fractures. Their clinical signs included reluctance to move the neck and head, dullness, and abnormalities of gait. Radiography was essential for the diagnosis, and the method of treatment varied depending on the severity of the neurological signs, the intended use of the horse, and financial constraints. Optimal treatment requires a technique that allows decompression, anatomical alignment, and stabilisation of the odontoid fracture. If the clinical (neurological) signs are not too severe and the animal shows signs of feeling peripheral pain, conservative treatment can be applied, as is common practice in human surgery. All except the pony made a full recovery.

Bacterial Cholangitis, Cholecystitis, or both in Dogs

Background Bacterial cholangitis and cholecystitis are rarely reported, poorly characterized diseases in the dog. Objectives To characterize the clinical features of these conditions. Animals Twenty‐seven client‐owned dogs with bacterial cholangitis, cholecystitis, or both. Methods Multicenter, retrospective cases series of dogs with bacterial cholangitis, cholecystitis, or both, presenting January 2000 to June 2011 to 4 Veterinary Schools in Ireland/United Kingdom. Interrogation of hospital databases identified all cases with the inclusion criteria; histopathologically confirmed cholangitis or cholecystitis and bile culture/cytology results supporting a bacterial etiology. Results Twenty‐seven dogs met the inclusion criteria with approximately 460 hepatitis cases documented over the same study period. Typical clinical pathology findings were increases in liver enzyme activities (25/26), hyperbilirubinemia (20/26), and an inflammatory leukogram (21/24). Ultrasound findings, although nonspecific, aided decision‐making in 25/26 cases. The most frequent hepatobiliary bacterial isolates were Escherichia coli (n = 17; 16 cases), Enterococcus spp. (n = 8; 6 cases), and Clostridium spp. (n = 5; 5 cases). Antimicrobial resistance was an important feature of aerobic isolates; 10/16 E. coli isolates resistant to 3 or more antimicrobial classes. Biliary tract rupture complicated nearly one third of cases, associated with significant mortality (4/8). Discharged dogs had a guarded to fair prognosis; 17/18 alive at 2 months, although 5/10 re‐evaluated had persistent liver enzyme elevation 2–12 months later. Conclusion and Clinical Significance Bacterial cholangitis and cholecystitis occur more frequently than suggested by current literature and should be considered in dogs presenting with jaundice and fever, abdominal pain, or an inflammatory leukogram or with ultrasonographic evidence of gallbladder abnormalities.

Tetanus in the dog: review and a case-report of concurrent tetanus with hiatal hernia

Tetanus with hiatal hernia was diagnosed in a four-month-old female sheepdog pup. The animal was treated with tetanus antitoxin, antibiotics, fluids and intensive nursing care for three weeks and subsequently made a full recovery.

IMAGING DIAGNOSIS: CT FINDINGS IN A DOG WITH INTRACRANIAL HEMORRHAGE SECONDARY TO ANGIOSTRONGYLOSIS

A seven-month-old Cocker Spaniel had a cough, acute lethargy, decreased responsiveness, and episodes of hyperexcitability. There were bilateral generalized increased lung sounds, bilateral episcleral hemorrhage, and systemic hypertension. Prolonged buccal mucosal bleeding time and elevated D-dimer concentrations were detected. Radiographically, there was a generalized moderate unstructured interstitial pattern. In thoracic CT images, there was a diffuse moderate hyperattenuating appearance of the bronchial walls and interstitium and diffuse areas of moderate bronchiectasis. The brain CT images were characterized by marked hyperattenuating well-defined masses. In addition, there were smaller hyperattenuating and hypoattenuating masses scattered throughout the cerebral and cerebellar parenchyma. A zinc sulphate flotation test confirmed large numbers of Angiostrongylus vasorum L1 larvae. Despite therapy the dog continued to deteriorate and underwent euthanasia. Postmortem examination confirmed the presence of multiple intracranial and extracranial hemorrhages. Angiostrongylosis should be considered as one of the differential diagnoses in dogs presenting with neurologic signs consistent with acute intracranial haemorrhage.