Determination of the acute oral toxicity of theophylline in conscious dogs

The purpose of this study was to define the minimum toxic concentrations and clinical signs of theophylline toxicity in healthy, conscious dogs. Five dogs were dosed orally in a five-way crossover design with sustained release theophylline (Theo-Dur tablets, Key Pharmaceuticals) at 0, 20, 40, 80, and 160 mg/kg. They were observed for a 9-h period for clinical signs of toxicity which had been previously determined in a pilot study. These signs included sinus tachycardia and central nervous stimulation (manifested as restlessness, excitement, or vomition). The Physiotel radiotransmitter telemetry system was used for the acquisition of the heart rate and ECG. Blood samples were obtained every hour for theophylline determination by high pressure liquid chromatography. The results showed that toxicity occurs at higher theophylline plasma concentrations in the dog (37-60 micrograms/ml) as compared to man (greater than 20 micrograms/ml) when dosed orally. Since current dosage regimens in dogs are designed to maintain trough-peak theophylline plasma concentrations between 10 and 20 micrograms/ml, the results indicate that the upper limit of this range appears to be safe in the dog.     

An intestinal neuroendocrine tumour associated with paroxysmal ventricular tachycardia and melaena in a 10-year-old boxer

A 10-year-old female neutered boxer was presented with a five-week history of episodic collapse and melaena. Twenty-four-hour electrocardiograph (Holter) analysis revealed the collapsing episodes to coincide with episodes of paroxysmal ventricular tachycardia. Investigation of the dog's melaena revealed a gastric ulcer which was treated medically and an ileocaecal mass which was surgically excised. Histopathological examination of the mass was consistent with a neuroendocrine (carcinoid) tumour. The patient's recovery after surgery was unremarkable. At six-week follow-up, there had been no further episodes of melaena or collapse and repeat Holter analysis did not show any significant abnormalities. In this dog the gastric ulceration and paroxysmal ventricular tachycardia could be attributed to a paraneoplastic syndrome as a result of circulating vasoactive substances released by the tumour; this is supported by the evidence that all clinical signs resolved after surgical excision of the mass and the dog was clinically well 18 months after surgery.     

Metaproterenol intoxication in a dog

Intoxication with metaproterenol, a mainly beta-2 selective agonist, was diagnosed in a dog with tachycardia, tachypnea, weakness, vomiting, and a history of exposure to the drug. Electrocardiography and echocardiography disclosed sinus tachycardia with episodes of ventricular tachycardia and exuberant systolic ventricular function, respectively. Administration of the beta blocking drugs propranolol and atenolol led to resolution of the clinical signs. Excessive sympathetic stimulation caused by metaproterenol is an unusual intoxication in dogs.     

Radiofrequency Catheter Ablation of Atrioventricular Accessory Pathways in 3 Dogs with Subsequent Resolution of Tachycardia-Induced Cardiomyopathy

Incessant supraventricular tachyarrhythmias are known to result in myocardial dysfunction indistinguishable from idiopathic dilated cardiomyopathy by current testing methods. This tachycardia-induced cardiomyopathy (TICM), however, is uniquely reversible with adequate rhythm control. Two dogs were presented to The Ohio State University for incessant supraventricular tachycardia (SVT) and echocardiographic signs of dilated cardiomyopathy, later proven to be TICM. A 3rd dog presented for frequent paroxysms of SVT and syncope had echocardiographic signs of mild myocardial systolic dysfunction. All 3 dogs had inadequate rhythm control with multiple antiarrhythmic agents, and 1 dog suffered from recurrent left-sided congestive heart failure. Generalized cardiomegaly was found in 1 dog and left-sided dilatation without concurrent right-sided enlargement in 1 dog. Mild-to-severe left ventricular systolic dysfunction was confirmed echocardiographically in all dogs. A total of 4 atrioventricular accessory pathways (APs) were found during invasive electrophysiologic studies in these 3 dogs. All APs were successfully ablated with radiofrequency energy delivered through a thermistor-tipped catheter. Elimination of AP conduction, and thus orthodromic atrioventricular reciprocating tachycardia, resulted in resolution of all clinical and echocardiographic evidence of TICM in these dogs. This result confirms that the cardiomyopathy was, in fact, reversible TICM. All cardiovascular medications were discontinued, and no complications occurred during a 15-25-month follow-up period.     

Dietary hyperthyroidism in dogs

Objectives: Evaluation of dogs with elevated plasma thyroxine concentration fed raw food before and after changing the diet. Method: Between 2006 and 2011 all dogs presented with an elevated plasma thyroxine concentration and a dietary history of feeding raw food were included. Thyroxine (reference interval: 19·3 to 51·5 nmol/L) and in many cases also thyroid-stimulating hormone concentrations (reference interval: <0·30 ng/mL) were measured initially and after changing the diet. Results: Twelve dogs were presented with a median age of five years. The median plasma thyroxine concentration was 156·1 (range of 79·7 to 391·9) nmol/L; in six dogs, thyroid-stimulating hormone concentration was measured and was <0·03 ng/mL in five dogs and 0·05 ng/mL in one dog. Six dogs showed clinical signs such as weight loss, aggressiveness, tachycardia, panting and restlessness while six dogs had no clinical signs. After changing the diet eight dogs were examined: thyroxine concentration normalised in all dogs and clinical signs resolved. Clinical Significance: Dietary hyperthyroidism can be seen in dogs on a raw meat diet or fed fresh or dried gullets. Increased plasma thyroxine concentration in a dog, either with or without signs of hyperthyroidism, should prompt the veterinarian to obtain a thorough dietary history.     

Long‐term Treatment with Methylene Blue in a Dog with Hereditary Methemoglobinemia Caused by Cytochrome b5 Reductase Deficiency

A juvenile male mixed breed dog was presented for lethargy, exercise intolerance, and aggression when touched on the head. Cyanosis, tachycardia, and tachypnea were observed and persisted during oxygen supplementation. Arterial blood gas analysis by co‐oximetry identified an increased methemoglobin concentration (27%; normal, <2%) with normal arterial oxygen tension. The methemoglobinemia and associated clinical signs resolved after administration of methylene blue (1 mg/kg) IV, and the dog was discharged. The affected dog's whole‐genome sequence contained 2 potentially causal heterozygous CYB5R3 missense mutations suggesting that cytochrome b5 reductase deficiency was responsible for the methemoglobinemia. This hypothesis was confirmed by enzyme analysis that identified cytochrome b5 reductase activity in the affected dog's erythrocytes to only approximately 6% of that in a control sample. Clinical signs recurred 11 days after discharge but normalized and the methemoglobin concentration decreased with methylene blue administration PO (1.5 mg/kg, initially daily and then every other day).     

Tachycardia-induced cardiomyopathy in a young Boxer dog with supraventricular tachycardia due to an accessory pathway

A 1-year-old male Boxer dog presented with sustained supraventricular tachycardia and tachycardia-induced cardiomyopathy. Conversion to sinus rhythm was achieved initially with intravenous lignocaine and subsequently with oral procainamide. Oral procainamide treatment was relatively successful in maintaining normal sinus rhythm with no side effects apart from a reversible change in coat colour. Electrophysiological studies demonstrated the presence of an accessory pathway connecting the right atrium to the right ventricle and confirmed the diagnosis of orthodromic atrioventricular reciprocating tachycardia. Radiofrequency catheter ablation of the accessory pathway led to permanent resolution of the supraventricular tachycardia and for 9.5 years the dog has had no further signs of cardiac disease. The successful treatment of this condition highlights the importance of differentiating tachycardia-induced cardiomyopathy from dilated cardiomyopathy.     

Arrhythmogenic right ventricular cardiomyopathy coincided with the cardiac fibrosis in the inner muscle layer of the left ventricular wall in a boxer dog

A 7-year-old female boxer dog died suddenly without any clinical signs. It was suspected that the dog had arrhythmogenic right ventricular cardiomyopathy (ARVC) due to ventricular premature complexes and ventricular tachycardia at 3 years of age. The final diagnosis of ARVC was confirmed by histological characteristics, such as loss of cardiocytes and fibrofatty replacement, occurring in the right and left ventricular walls. In the cardiocytes, non-lipid vacuoles were observed. Cardiac fibrosis and intimal thickening of the small arteries occurred without fatty replacement in the inner muscle layer including the papillary muscles of the left ventricular wall. This paper describes the pathomorphological details of an ARVC case with coincidental cardiac fibrosis in the inner muscle layer of the left ventricular wall.     

Successful treatment of canine necrolytic migratory erythema (superficial necrolytic dermatitis) due to metastatic glucagonoma with octreotide

Necrolytic migratory erythema (NME; also known as superficial necrolytic dermatitis) is a syndrome most often associated with certain chronic liver diseases or pancreatic glucagonomas. In humans with glucaconoma‐associated NME, skin lesions usually respond to octreotide, a somatostatin analogue that inhibits glucagon release. In this report an 11‐year‐old golden retriever dog with pancreatic glucononoma and metastasis to the regional lymph nodes, spleen and liver was diagnosed with NME. The dog exhibited erosions, ulcers and crusts on the paws, pressure points, muzzle, periocular area and prepuce. The dog was also anorexic and had difficulty walking. Because metastasis precluded surgery, treatment was initiated with subcutaneous octreotide (2 μg/kg twice daily). Skin lesions and systemic clinical signs improved markedly within 5 days. The dosage was increased to nearly 3 μg/kg twice daily and signs almost completely resolved within 10 days. Anorexia was the major adverse effect observed. During the following month, both dosage (1–3.7 μg/kg) and frequency (two to four times daily) of the octreotide injections were adjusted to permit control of clinical signs while maintaining adequate appetite. Temporary cessation of octreotide administration resulted in the rapid recurrence of skin lesions. Resuming injections led to improvement of clinical signs within 48 h. The dog was later euthanized because of progressive metastatic disease. In conclusion, subcutaneous octreotide injections were beneficial in this dog with glucagonoma‐associated NME. This somatostatin analogue could be a valuable option to treat canine patients with non‐resectable or relapsing pancreatic glucagonoma‐associated NME.     

Allergic inhalant dermatitis attributable to marijuana exposure in a dog

Exposure to marijuana was believed to be responsible for clinical signs consistent with allergic inhalant dermatitis in a dog. The dog had facial and pedal pruritus associated with bilateral ocular discharge. Clinical signs resolved when the dog was kenneled, but returned when the dog was returned to its home. The results of intradermal skin testing, using a standard tray of 51 inhalant extracts, did not adequately account for the dog's clinical signs. Later, the owners indicated that previous residents of the owners' home had cultivated marijuana intensively inside and outside of the home. Intradermal skin testing with a source of marijuana pollen extract was performed, yielding a positive reaction in the dog and a negative reaction in another dog without clinical or historical evidence of allergic inhalant dermatitis. The affected dog was treated successfully and exclusively by hyposensitization with marijuana pollen extract.     

Clinical effects of bovine lactoferrin on two canine cases with familial neutrophil dysfunction

This study reported detailed clinical effects of bovine lactoferrin on 2 canine littermates (1 female and 1 male) with familial neutrophil dysfunction and an investigation of their genetic background. Clinical signs caused by severe upper respiratory bacterial infections were observed in these dogs. Oral administration of bovine lactoferrin for a long duration improved their clinical signs (severe uveitis in the female dog and coughing from pneumonia in the male dog). Their backcross dogs that have the same father didn't show clinical signs of bacterial infection. Neutrophil function tests revealed that the backcross dogs didn't have any disorders. It is likely that abnormal clinical signs are associated with neutrophil dysfunction in the colony, and the mother dog of these cases might be the genetic carrier of this dysfunction.     

Functional thyroid gland adenoma in a dog treated with surgical excision alone

An 11-year-old male Golden Retriever presented with progressive weight loss, tachycardia, hyperthermia, polyuria and polydipsia. A freely movable mass, 4.5 x 4 cm in size, was palpated at the cranioventral cervical region. Hormonal study revealed high levels of serum thyroid hormones, and a tentative diagnosis of hyperthyroidism due to a thyroid tumor was made. The tumor was removed surgically and diagnosed histopathologically as thyroid gland adenoma. Serum thyroid hormone levels decreased after surgery with improved clinical signs. At 12 months after surgery, the dog maintained a good physical condition with no evidence of recurrence.     

Peptic ulceration in a dog associated with an islet cell carcinoma of the pancreas and an elevated plasma gastrin level

The history, clinical signs and post-mortem findings in a 6-year-old, male, Boxer dog with peptic ulceration and a tumour derived from islet cells of the pancreas are described. The immunoreactive circulating plasma gastrin in this dog was elevated and measured 360 pg/ml (normal range 23–104 pg/ml). The findings in this dog are similar to those described for Zollinger-Ellison syndrome in man. It is possible that the pathogenesis of peptic ulceration in this case is similar to that of Zollinger-Ellison syndrome.     

Case-control study of canine infection by a newly recognised Babesia microti-like piroplasm

We did a case-control study to identify risk factors for prevalent infection of dogs by a newly recognised Babesia microti-like piroplasm. Clinical manifestations and haematology of infected dogs also were described. Forty-three laboratory-based cases and 86 individually matched controls were studied. Information on clinical signs and on risk factors was collected by a questionnaire and telephone interviews. Haematology was carried out for all the dogs. Variables were screened in a bivariable conditional logistic regression and checked for colinearity. The final multivariable model was selected by backward stepwise elimination. The odds of a case having ticks when examined at the clinic was 4 times that of a control and the odds of a case being a hunting or a house-guarding dog were, respectively, 24.2 and 2.7 times those of a control. The most consistently reported clinical signs were weakness (79%), tachycardia (43%) and haemoglobinuria (42%). Mean red-blood-cell count, haemoglobin concentration, platelet count, and mean platelet volume of infected dogs were lower than the reference values and those of non-infected dogs-but leukocyte count, mean corpuscular volume and red-blood-cell distribution width were higher.     

Natural infections of Crenosoma vulpis and Angiostrongylus vasorum in dogs in Atlantic Canada and their treatment with milbemycin oxime

Milbemycin oxime was used to treat dogs with natural infections of the fox lungworm, Crenosoma vulpis and the French heartworm, Angiostrongylus vasorum. Crenosomosis was identified in 42 of 202 dogs with clinical signs of coughing, dyspnoea or exercise intolerance by a Baermann analysis of faecal samples taken between October 2000 and October 2001. It occurred throughout Atlantic Canada (New Brunswick, Newfoundland, Nova Scotia and Prince Edward Island). The clinical signs resolved and shedding of larvae in faeces ceased in all 32 Crenosoma-infected dogs given a single oral dose of 0.5 mg/kg milbemycin oxime for which the results of faecal examinations were available. Angiostrongylosis was identified in 16 of the 202 dogs and was restricted to the Avalon peninsula of Newfoundland, where 67 dogs were tested. The clinical signs resolved and shedding of larvae ceased in 14 of the 16 dogs treated with four, weekly oral doses of 0.5 mg/kg milbemycin oxime. One dog with severe clinical signs died during the course of treatment and one owner failed to provide a faecal sample from their dog but reported that the clinical signs had resolved.     

Diagnosis and treatment of peritonitis caused by a larval cestode Mesocestoides spp., in a dog.

Infection of the peritoneal cavity with cestode larvae, presumptively diagnosed as tetrathyridia of the genus Mesocestoides, was found by exploratory celiotomy in a dog with clinical signs consisting of episodic anorexia, vomiting, and depression. Lymphopenia and hypoalbuminemia were associated clinicopathologic abnormalities. Dystrophic calcification and midline duodenal displacement were found on abdominal radiographs. Therapy with mebendazole was instituted after recurrence of the initial episodic clinical signs postoperatively. Daily use of mebendazole for intermittent periods of up to 3 months led to remission of gastrointestinal signs for 30 months. However, 17 months after the initial diagnosis, infection of the vaginal tunic of the testicle with similar cestode larvae necessitated castration and removal of the vaginal tunic to the inguinal ring. Mebendazole therapy was reinstituted and continued for 31/2 months postoperatively. The dog was free of clinical signs of infection during and for the 16 months since this period of treatment.     

Acute overdose of levothyroxine in a dog.

An overdose of up to 850 levothyroxine sodium tablets (0.2 mg) in a healthy 6-year-old 16.8-kg dog induced an episode of vomiting and hippus within 9 hours of ingestion. The dog was treated with activated charcoal and saline (magnesium sulfate) cathartic. Initially the serum concentration of thyroxine (T4) 4,900.9 nmol/L. On the second day, serum concentration of triiodothyronine (T3) was 5.3 nmol/L. Serum T4 concentration decreased slowly and was not determined to be normal until day 36. Serum T3 concentration was found to be normal on day 6. Serum alanine transaminase activity peaked on day 6 at 345 U/L. Significant abnormalities were not found during the following 36 days. Clinical signs of thyroid hormone toxicosis in dogs and cats include hyperactivity, lethargy, tachycardia, tachypnea, dyspnea, abnormal pupillary light reflexes, vomiting, and diarrhea. High overdoses of levothyroxine sodium in dogs should be managed by initial decontamination and administration of activated charcoal with a cathartic followed by supportive care.     

Toxic Myopathy in a Dog Associated with the Presence of Monensin in Dry Food

This report describes a case of toxic myopathy in a two year old sheltie dog with clinical signs of profound weakness, myoglobinuria, and muscle enzyme elevations. The clinical signs were likely related to the accidental inclusion of monensin sodium in the dog's food. This food was prepared by a small feed milling company that also prepares cattle and chicken rations. A change of dog food resulted in remission of the clinical signs.     

Hyperadrenocorticism in 10 dogs with skin lesions as the only presenting clinical signs

Ten dogs that had skin lesions as the only presenting signs of hyperadrenocorticism (HAC) and as the owners' primary complaint are described. Dogs were included if the initial examination was for skin disease, there were no signs of systemic illness on initial presentation and there was a confirmed diagnosis of HAC by specific screening tests. Dogs were excluded if they had a severe disease that might interfere with screening tests for HAC or if the screening tests were not diagnostic. There were five males and five females; six dogs were intact. Nine dogs were diagnosed at ≥7 years. Eight dogs weighed ≤10 kg. Alopecia was present in nine dogs. Eight dogs had bacterial pyoderma, five had hyperpigmentation, and four had thin skin. One dog had unresolved dermatophytosis. Skin lesions resolved after treatment in eight dogs. One dog was not treated and one was lost to follow-up. This study showed that skin lesions may be the only clinical signs of HAC. The presence of the more common clinical signs of HAC, such as a non-pruritic, truncal alopecia and/or thin skin, without any systemic signs of HAC and/or the presence of poorly responsive skin infections warrant screening for this disease.     

Neurologic manifestations of trypanosomiasis in a dog

A 13-month-old Doberman Pinscher was evaluated because of slowly progressive paraparesis and signs of depression. The dog had temporal, supraspinatus, and infraspinatus muscle atrophy, bilateral enophthalmos, superficial inguinal lymphadenopathy, tachycardia with pulse deficits, and lesions of active and inactive chorioretinitis. Neurologic abnormalities included hyperreflexic patellar reflexes, lack of conscious proprioception, signs of superficial pain in the hind limbs, and depressed hopping reflexes in the forelimbs. Cranial nerve abnormalities included decreased sensation in the left nostril and a delayed gag reflex. Results of cerebrospinal fluid analysis were characteristic of nonsuppurative inflammation. A diagnosis of multifocal neurologic disease was made. The dog did not have serum titers for fungal diseases, canine distemper, Ehrlichia canis infection, borreliosis, Rocky Mountain spotted fever, or toxoplasmosis. The dog did not respond to various antimicrobial treatments, and only slightly responded to corticosteroid treatment. The dog died during an anesthetic procedure. The postmortem diagnosis of Trypanosoma cruzi infection (canine Chagas disease) was made on identification of the amastigote form of the organism in sections of brain, spinal cord, and myocardium.