Use of radiographic measurements in distinguishing myasthenia gravis from other causes of canine megaoesophagus

OBJECTIVES: To evaluate whether dogs with megaoesophagus due to myasthenia gravis display less oesophageal dilatation radiographically than dogs with other causes of megaoesophagus. METHODS: Thoracic radiographs of 66 dogs with megaoesophagus in which concurrent acetylcholine receptor antibody titre was known were analysed retrospectively. Maximum oesophageal diameter was transformed to a "relative oesophageal diameter" using a ratio with thoracic inlet diameter. Dogs were divided into two groups according to "MG" or "non-MG" antibody status and median relative oesophageal diameter values were compared between groups and with age, weight and sex. A receiver operating characteristic plot was used to evaluate a suitable relative oesophageal diameter cut-off. RESULTS: Twenty dogs were diagnosed with myasthenia gravis and 46 with other causes of megaoesophagus. Thoracic inlet size correlated significantly with bodyweight and surface area (r(2)=0.627 and 0.669, respectively). Median values of relative oesophageal diameter for the MG group and non-MG group were 0.58 and 0.66, respectively, and these showed a small, but significant, difference (P=0.029), although there was complete overlap in the range of relative oesophageal diameter values between groups. There was no significant association between relative oesophageal diameter and sex, age or weight or significant difference in age, sex or weight between the two groups. An increased odds ratio for myasthenia gravis existed in golden retrievers and German shepherd dogs. CLINICAL SIGNIFICANCE: Relative oesophageal diameter appears to be of limited diagnostic utility in distinguishing dogs with megaoesophagus due to myasthenia gravis from those with megaoesophagus due to other causes.     

Oesophageal compliance in naturally occurring canine megaoesophagus

SUMMARY The passive blomechanical property of oesophageal compliance (OC) was measured in 8 naturally occurring cases of canine megaoesophagus, 8 matched control and 7 vagotomised control dogs. Of the 8 dogs with megaoesophagus, 6 had congenital Idiopathic megaoesophagus and 2 had secondary megaoesophagus attributable to generalised skeletal muscle disease. Stepwise distension of the whole oesophagus was employed for measurement of OC at the 4.0 and 8.0 mL/kg Injected volume steps within the control volume range (0 to 12.0 mL/kg). At both Injected volume steps OC was higher In megaoesophagus dogs than in either matched control or vagotomised control dogs (P / 0.01 In both cases), and no significant difference was observed In OC between matched control and vagotomised control dogs. No correlation was demonstrated between OC and the estimated duration of clinical signs of dogs with megaoesophagus. These findings suggest that In most cases of canine megaoesophagus the viscoelastic properties of the oesophageal wall are significantly altered, that In such cases the disorder is unlikely to be purely dynamic and that processes other than the duration of oesophageal dilatation are responsible for the alteration in oesophageal wall blomechanical properties. The relevance of these findings to current concepts on pathophysiological mechanisms underlying the evolution and resolution of various forms of canine megaoesophagus Is discussed.     

Canine myasthenia gravis

Decreased acetylcholine receptor content of the neuromuscular junction underlies the muscular weakness seen in both acquired and congenital myasthenia gravis. Immune mediated mechanisms account for the acquired defect while decreased membrane insertion of receptor leads to the congenital disorder. The congenital form typically presents in the first few weeks of life with generalised episodic weakness as the predominant sign. Although treatment with cholinesterase inhibitors may help temporarily, the prognosis is poor. Acquired myasthenia gravis can occur between eight months and 13 years of age and may present as megaoesophagus alone or as exercise-related weakness in conjunction with megaoesophagus. Although treatment of the immune mediated form is often successful and spontaneous remissions also occur, aspiration pneumonia secondary to megaoesophagus remains a major cause of mortality in affected dogs. Resolution of megaoesophagus must therefore be a major goal for future treatment regimes. The remarkable similarity between canine and human acquired myasthenia gravis suggests that the canine thymus gland warrants greater attention pathologically and perhaps therapeutically considering the value of thymectomy in human patients.     

Dynamic adrenal function testing in eight dogs with hyperadrenocorticism associated with adrenocortical neoplasia.

The results of adrenocorticotropin (ACTH) stimulation and low-dose dexamethasone suppression tests (LDDST) were evaluated retrospectively in eight dogs with clinical signs of hyperadrenocorticism arising from functional adrenocortical tumours, and compared with the results from 12 dogs with confirmed pituitary-dependent hyperadrenocorticism (PDH). The post-ACTH cortisol concentration in the dogs with adrenocortical tumours ranged from 61 to 345-6 nmol/litre (median 251.5 nmol/litre) and they were within the reference range (150 to 450 nmol/litre) in five and unexpectedly low (< 150 nmol/litre) in three dogs. Both the basal and post-ACTH cortisol concentrations were significantly lower in the dogs with adrenocortical neoplasia than in the dogs with PDH. Eight hours after the LDDST, only two of six dogs with adrenocortical tumours had a cortisol concentration above 30 nmol/litre, and the median resting, three, and eight-hour cortisol concentrations were 31.5, 23.0, and 22.7 nmol/litre respectively. There was no significant cortisol suppression during the LDDST, although interpretation was complicated by the low cortisol concentrations, but two dogs showed a pattern of apparent suppression. Two dogs with adrenal tumours showed a diagnostically significant increase in 17-OH-progesterone concentration in response to ACTH although their cortisol concentrations did not increase greatly. These results differ from previous reports of the response of functional adrenal tumours to dynamic endocrine tests.     

Validation of a radioassay for the determination of serum folate and cobalamin concentrations in dogs

Determinations of serum folate and cobalamin concentrations in dogs have proved of considerable value for the identification and characterisation of chronic small intestinal disorders, but the microbiological assays used are time-consuming and technically demanding. Dual isotope radio-assays are more convenient and have been developed for the determination of folate and cobalamin in human beings. This study has evaluated such an assay for the determination of serum folate and cobalamin concentrations in dogs by direct comparison with microbiological assays used previously. Assays were performed on samples from 77 dogs, including controls and animals with confirmed or suspected chronic small intestinal disease. Regression analysis demonstrated a significant relationship between the two assays for serum folate concentrations (R=0–85; P=0–0001) and a definite trend for radioassay to give lower results than bioassay. There was also a significant relationship between bioassay and radioassay data for serum cobalamin (R=0–91; P=0–0001) with comparable absolute values for these two assays. Radioassay of serum samples from 31 clinically healthy dogs gave control ranges of 3–7 to 8-8 4mUg/litre for folate and 205 to 490 ng/litre for cobalamin. These ranges were similar to those calculated by comparison with the established ranges for bioassay using regression analysis, which predicted ranges of 4-4 to 8-4 μg/litre and 217 to 398 ng/litre for radioassay of serum folate and cobalamin, respectively. These data indicate that a dual isotope radioassay of serum folate and cobalamin may be used for dogs, and emphasise the need for laboratories to validate and establish their own control ranges for different assays.     

Treatment of acquired myasthenia gravis associated with thymoma in two dogs

Two cases of myasthenia gravis associated with thymoma are reported. Both were female German shepherd dogs and the thymoma was surgically resected. Aspiration pneumonia secondary to persistent megaoesophagus was a complication in both cases. The myasthenia gravis did not resolve, but there was a more satisfactory control of clinical signs with anticholinesterase treatment. Corticosteroid therapy was used in one case, but the resulting polydipsia increased the incidence of regurgitation, resulting in recurrent episodes of aspiration pneumonia.     

Evaluation of the basal and post-adrenocorticotrophic hormone serum concentrations of 17-hydroxyprogesterone for the diagnosis of hyperadrenocorticism in dogs

Serum concentrations of 17-hydroxyprogesterone and cortisol were measured before and after the administration of exogenous adrenocorticotrophic hormone (ACTH) to three groups of dogs: 27 healthy dogs (group 1), 19 dogs with non-adrenal illness (group 2) and 46 dogs with hyperadrenocorticism (group 3). The median (range) post-ACTH concentrations of 17-hydroxyprogesterone were 5.0 (22.2 to 16.8), 6.9 (2.0 to 36.2) and 14.4 (1.7 to 71) nmol/litre in groups 1, 2 and 3, respectively. There were no significant differences in the basal or post-ACTH concentrations of cortisol or 17-hydroxyprogesterone between groups 1 and 2. The post-ACTH concentrations of 17-hydroxyprogesterone in group 3 were significantly (P<0.001) greater than those in groups 1 and 2 combined. The area under the receiver operating curve (ROC) for the post-ACTH concentration of cortisol (0.94) was significantly greater than that for the post-ACTH concentration of 17-hydroxyprogesterone (0.76). Using a two-graph ROC analysis, a cut-off of 8.5 nmol/litre was found to maximise both the sensitivity and specificity of the post-ACTH concentration of 17-hydroxyprogesterone for the diagnosis of hyperadrenocorticism at 71 per cent. With a cut-off of 4.5 nmol/litre the sensitivity increased to 90 per cent but the specificity decreased to 40 per cent; with a cut-off of 16.7 nmol/litre the specificity increased to 90 per cent but the sensitivity decreased to 47 per cent.     

Treatment and therapeutic monitoring of canine hypothyroidism

Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone replacement therapy (THRT) and monitored for approximately three months. Good clinical and laboratory control was ultimately achieved in all cases with a mean L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a significant increase and decrease in circulating total T4 and canine thyroid stimulating hormone (cTSH) concentrations, respectively, after starting THRT. After commencing treatment, 11 cases subsequently required an increase and three cases required a decrease in dose to achieve optimal clinical control. Median (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6 [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were significantly increased and decreased, respectively, in treated dogs that did not require a dose change; corresponding values in treated dogs in which an increase in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre, respectively. However, circulating cTSH measurement was of limited value in assessing therapeutic control because, although increased values were associated with inadequate therapy, reference range cTSH values were common in inadequately treated dogs. Lethargy and mental demeanour were typically the first clinical signs to improve, with significant bodyweight reduction occurring within two weeks of commencing THRT. Routine clinicopathological monitoring was of value in confirming a general metabolic response to THRT, but was of limited value in accurately monitoring cases or tailoring therapy in individual cases.     

The neuropathic oesophagus. A radiographic and manometric study on the evolution of megaoesophagus in dogs with developing axonal neuropathy

Dogs given the neurotoxin acrylamide develop peripheral neuropathy and megaoesophagus. Sequential radiographic and manometric studies on the oesophagus demonstrated that the initial abnormalities consisted of a progressive decrease in the proportion of swallows that initiated peristalsis and a gradual increase in oesophageal calibre. Regurgitation, peristaltic failure and oesophageal dilatation all appeared within three days. The eating behaviour and gait abnormalities quickly resolved on stopping the neurotoxin, but the oesophagus remained dilated for longer. Previous studies have suggested that the abnormalities present in dogs which are developing a distal axonal neuropathy or in some dogs with idiopathic megaoesophagus may be limited to the proprioceptive elements of the oesophageal innervation. The present study suggests that the progressive inefficiency in the transmission of swallows and changes in oesophageal calibre in dogs with evolving megaoesophagus may be a consequence of damage to these proprioceptive elements.     

Urinary alkaline phosphatase and 7-glutamyl transferase as indicators of acute renal damage in dogs

Urinary alkaline phosphatase (AP) and 7-glutamyl transferase (GGT) levels were measured in normal dogs, dogs with chronic renal failure, and dogs with acute renal failure, as confirmed by renal histology. The median values for urinary AP were 5–8 iu/litre/mmol creatinine for normal dogs, 6–7 for dogs with chronic renal failure and 49-4 for dogs with acute renal failure. The median values for urinary GGT were 3–4 iu/litre/mmol creatinine for normal dogs, 4–9 for dogs with chronic renal failure and 9-6 for dogs with acute renal failure. The results suggest that urinary AP can be used as an indicator of acute renal damage in the dog. GGT was shown to be less useful. No clear correlations were found between urinary enzyme levels and the extent of morphological kidney damage.     

Hypercalcaemia in the dog: a study of 40 cases

Forty dogs referred to the University Department of Clinical Veterinary Medicine, Cambridge for medical and oncological conditions between 1985 and 1990 were found to be hypercalcaemia In 18 cases the primary or underlying condition was diagnosed as lymphoproliferative disease with multicentric lymphoma occurring most commonly. Ten dogs were suffering from hypoadrenocorticism (Addison's disease) and two had adenocarcinomas of the apocrine glands of the anal sac. In three dogs a clinical diagnosis of renal dysplasia was made, this diagnosis being confirmed at post mortem examination in one dog. In the remaining cases hypercalcaemia was associated with a primary lung tumour, a thymoma, an osteosarcoma with widespread skeletal metastases, primary hyperparathyroidism due to a parathyroid adenoma, chronic panniculitis, iatrogenic hypoadrenocorticism following mito-tane therapy (one case each] and, in a further case, no diagnosis was reached. The most common clinical signs were inappetence, polyuria/ polydipsia, weakness, vomiting, lethargy and depression. As a group, the dogs with lymphoproliferative disease had a significantly higher mean plasma calcium concentration (4-3 ± 0–7 vs 3–5 ± 0–4 mmol/litre), a significantly lower mean plasma inorganic phosphate concentration (1–5 ± 0–5 vs 2–4 ± 09 mmol/litre) and were significantly older (5-5 ± 2–4 vs 3-3 + 1–8 years) than the dogs with hypoadrenocorticism.     

Renal clearance studies in cats with chronic renal disease: Dietary implications

Renal clearance studies were undertaken on 15 cats, 10 with mild chronic renal disease (CRD) and five with severe CRD. Plasma creatinine concentration and urinary specific gravity measurements in the mild and severe CRD cats were significantly different (P < 0–05) and were 131 ± 26-7 umol/litre and 1–034 ± 0–016, and 392 ± 117-3 nmol/litre and 1–015 ± 0–002, respectively. Endogenous creatinine clearance in the mild and severe CRD cats were significantly different (P < 0–01) and were 2–3 ± 0–58 and 0–62 ± 0–230 ml/min/kg bodyweight, respectively. Hypokalemia was present in one cat but it was not associated with hypercalcinuria. Two cats with mild CRD had hypophosphataemia, hypercalcaemia and hyperphosphaturia which was suggestive of primary hyperparathyroidism, while two cats with severe CRD had hyperphosphataemia and hyperphosphaturia which was indicative of renal secondary hyperparathyroidism. Eight of the 15 cats were subsequently necropsied and were found to have segmental atrophic nephropathy.     

Megaoesophagus and glucocorticoid-deficient hypoadrenocorticism in a dog

A seven-year-old German shepherd dog was referred for acute onset regurgitation. Muscle weakness and severe dermatological disease were present. Thoracic radiographs revealed generalised megaoesophagus. Diagnostic testing revealed glucocorticoid deficiency, and rapid resolution of the megaoesophagus followed appropriate supplementation. The dog made a full recovery. Unique features of this case include a transiently positive antinuclear antibody titre and clinical features of myasthenia gravis.     

Dynamic pulmonary compliance as a measurement of lung function in dogs

Measurement of the dynamic pulmonary compliance was carried out on 27 normal dogs weighing 11-8 to 26-4 kg Variations in the results of repeated observations and difficulties in allowing for differences in lung size between dogs limited the usefulness of the measurement as a test of lung function. Pulmonary compliance was found to correlate better with trunk length than with bodyweight or chest circumference. The mean value for dynamic pulmonary compliance measured during inspiration in 27 normal dogs was 0-117 litre/cmH20 with a standard deviation of 0-046 litre/cmH2O. Measurements were made on six dogs with clinical respiratory disease.     

Plasma Taurine Concentrations in Normal Dogs and in Dogs With Heart Disease

Plasma taurine concentrations were determined in 76 dogs with dilated cardiomyopathy (DCM), 28 dogs with acquired valvular disease (AVD), and 47 normal (control) dogs. The data were collected at 2 referral centers. The Animal Medical Center, New York, NY (AMC), and the University of California, Davis (UCD), and the studies were conducted independently. Different anticoagulants (sodium citrate at AMC and lithium heparin at UCD) were used to collect the plasma samples. Paired analysis of samples showed a significant difference in plasma taurine concentrations, depending on the anticoagulant used. Consequently, results from each clinic were analyzed separately. Plasma taurine concentrations were significantly higher in dogs with AVD (median, 133 nmol/mL; range, 25 to 229 nmol/mL) than in control dogs (median, 63 nmol/mL; range 44 to 224 nmol/mL) and dogs with DCM (median, 72 nmol/mL; range, 1 to 247 nmol/mL) at AMC (P= .001). The number of dogs with AVD at UCD was too small to draw meaningful conclusions. At UCD, the median plasma taurine concentration was 98 nmol/mL (range, 28–169 nmol/mL) in dogs with AVD, 75 nmol/mL (range, 0.1–184 nmol/mL) in dogs with DCM, and 88 nmol/mL (range 52–180 nmol/mL) in control dogs. There were no significant differences in plasma taurine concentrations between dogs with DCM and the control dogs at either hospital. Congestive heart failure and administration of cardiac medication had no significant effect on plasma taurine concentrations. Plasma taurine concentration was low (<25 nmol/mL) in 17% (13/76) of the dogs with DCM. Seven of the 13 dogs with low plasma taurine concentrations were Cocker Spaniels or Golden Retrievers. It was concluded that most dogs with DCM do not have low plasma taurine concentrations. However, certain breeds or individual dogs may have low plasma taurine concentrations in association with DCM. Whether this association is causal or not is unknown. The significance of the high plasma taurine concentrations in dogs with AVD is also unknown.     

Megaoesophagus in adult dogs secondary to Australian tiger snake envenomation

Four cases of megaoesophagus secondary to tiger snake envenomation are reported. History in all cases suggested megaoesophagus was not present prior to snake envenomation. Diagnosis of megaoesophagus was confirmed by thoracic radiography in all cases. One dog died of respiratory failure. The remaining three dogs recovered, with gradual resolution of clinical signs associated with megaoesophagus.     

Trilostane treatment of 78 dogs with pituitary-dependent hyperadrenocorticism

The efficacy of trilostane in the treatment of canine pituitary-dependent hyperadrenocorticism (PDH) was evaluated in 78 dogs with the condition which were treated for up to three years. The drug appeared to be well tolerated by almost all the dogs, and only two developed clinical signs and biochemical evidence of hypoadrenocorticism. Polyuria and polydipsia completely resolved in 70 per cent of the dogs that had these problems, and skin changes resolved in 62 per cent of the dogs that had skin abnormalities. There was a significant reduction (P<0.001 in each case) in both the mean basal and post-adrenocorticotrophic hormone (ACTH) cortisol concentrations after a mean of 12.3 days of treatment. The post-ACTH cortisol concentration decreased to less than 250 nmol/litre in 81 per cent of the dogs within one month of the start of treatment and in another 15 per cent at some later time. The median survival time of the 26 dogs which died was 549 days, and 51 of the dogs were alive at the completion of the study. One was lost to follow up after 241 days treatment.     

Termination of mid-term pregnancy in the dog with oral RU 486

A total of four pregnancies were terminated in three bitches (two beagles and one flatcoated retriever) with a single dose of 20 mg/kg (one case), two doses of 8-3 mg/kg (one case) or 20 mg/kg plus 40 mg/kg (two cases) RU 486 by mouth (Mifepristone; Roussel-Uclaf, France) from day 26 to day 36 after the first day of mating of the bitch. Abortions occurred within two, four, 11 and 11 days after the initial treatment, respectively. The clinical status of the bitches was similar to that observed during a normal parturition, ie, lowering of the body temperature, shivering, panting and nesting behaviour. No side effects were seen. The beagle bitch that aborted twice, was mated at the first oestrus after the first abortion, conceived and aborted the same number of puppies the second time. The peripheral plasma progesterone concentration at the time of treatment in all bitches was < 75 nmol/litre. It had decreased to between 24-2 and 13-1 nmol/litre at the time of abortion and to between 4-0 to 0–5 nmol/litre at four to 15 days after the initial treatment. Peripheral plasma levels of prolactin increased three- to fourfold within 24 to 48 hours after treatment, concomitant with the drop in progesterone and had returned to basal levels within two to three days. Prolactin concentrations also increased around the time of intrauterine fetal death. Prostaglandin F_2aα-metabolite concentrations increased slowly after treatment, and around the time of abortion the levels increased five- to 10-fold. RU 486 seems to be a safe and effective abortifacient for use during mid-term pregnancy in the dog.     

Diagnosis of insulinoma in the dog: A study of 11 cases

The use of an intravenous glucose tolerance test (IVGTT) is described in 11 confirmed cases of insulinoma. Basal plasma glucose and serum insulin concentrations, glucose half-life (t.J and fractional clearance rate (k-value) were determined in the affected animals and seven healthy dogs. A fasting plasma glucose concentration of 3 mmol/litre or less with a coexisting serum insulin concentration greater than 20 mU/litre, and an insulin:glucose ratio (IGR) greater than 4-2 U/mol were considered to be diagnostic for insulinoma. Although there was a narrow area of overlap in the U₂ and k-values between normal and affected animals, a t.,₂ of less than 20 minutes with a k-value of more than 3 per cent/minute were also highly suggestive of insulinoma. The insulinogenic index (δI/δG) was too variable to be of diagnostic significance. Contrary to previous reports, it appears that insulin-secreting tumours retain a degree of responsiveness to a glucose challenge and that the IVGTT, using a dose of 0–5 g glucose/kg bodyweight, is a useful diagnostic procedure in dogs with insulinoma.     

Surgical correction of gastro‐oesophageal intussusception with bilateral incisional gastropexy in three dogs

Three dogs presented for evaluation of acute onset tachypnoea and dyspnoea following episodes of vomiting and/or regurgitation. Thoracic radiographs were suggestive of a gastro‐oesophageal intussusception in all three dogs; one dog also showed evidence of aspiration pneumonia. All three dogs underwent surgical correction with a bilateral incisional gastropexy. All dogs recovered from anaesthesia uneventfully and were discharged from the hospital 3 days after presentation. Persistent megaoesophagus was evident in all three dogs, and they are being chronically managed with a strict feeding regime and pro‐motility agents.