Effects of continuous alpha (1-24) ACTH infusion in the dog.

Dogs chronically infused with alpha (1-24) ACTH for 2 weeks showed continuous elevations in plasma ACTH, cortisol, and progesterone levels. Haematologic changes included immediate increases in numbers of mature neutrophils and monocytes and reduced numbers of eosinophils and lymphocytes. Haematocrits were also reduced with ACTH infusion. Whereas serum potassium levels fell in association with ACTH, serum sodium was unchanged. Activities of two serum enzymes of probable liver origin, alkaline phosphatase and alanine aminotransferase, increased gradually with ACTH treatment. Histologic examination of liver tissue revealed prominent hepatocellular vacuolisation. The trophic action of ACTH infusion was manifested by an increased adrenal gland weight and an enhanced cortisol response to a bolus ACTH injection given 1 day after the infusion ceased. Long-term infusion of ACTH resulted in haematologic, biochemical and morphologic changes resembling those observed in dogs with spontaneous pituitary-dependent hyperadrenocorticism.

Serum thyroxine and triiodothyronine concentrations in canine pyoderma.

In an effort to evaluate the effect of pyoderma on circulating iodothyronines, plasma triiodothyronine (T3) and thyroxine (T4) values were determined before and after thyroid stimulating hormone administration in 25 dogs with pyoderma and in 15 controls. Basal T4 values were increased in dogs with pyoderma, but neither stimulated T4 nor T3 values were altered by this condition. On the basis of low values for circulating iodothyronines, hypothyroidism was suspected in 3 dogs in the pyoderma group. The dog with the most involved lesions had extremely low T3 and T4 values as well as an autoimmune disease. It was concluded that most dogs with pyoderma do not have thyroid dysfunction.

Effect of prednisone on thyroid gland morphology and plasma thyroxine and triiodothyronine concentrations in the dog.

The effects of multiple IM injections of prednisone (2.2 mg/kg) on thyroid morphology and on plasma thyroxine (T4) and triiodothyronine (T3) concentrations in dogs were determined, and the effects of a single prednisone injection on the same circulating iodothyronine concentrations were assessed. Plasma T4 and T3 concentrations decreased significantly after 3 injections of prednisone were made. However, with a single prednisone injection, there was no significant difference in plasma T4 values between control and treated animals. Starting at 8 hours after a single prednisone injection and continuing through day 2, plasma T3 values were significantly lowered. Prednisone treatment also resulted in significantly more thyroid cytoplasmic colloid droplets per follicular cell (3.19 vs 0.57 in treated and control dogs). Lysosomal hydrolysis of colloid appeared to be inhibited by glucocorticoids in dogs, resulting in an alteration of normal thyroid gland functioning.

Use of a low dose synthetic ACTH challenge test in normal and prednisone-treated dogs.

The utility of a low dose (1 microgram/kg) synthetic ACTH challenge test in detecting moderate reductions in adrenocortical sensitivity in dogs was examined. First, the adrenocortical responses to an intravenous bolus of either 1 microgram/kg or 0.25 mg per dog of synthetic ACTH were compared in two groups of normal dogs. While plasma cortisol concentrations were similar in both groups 60 minutes after ACTH injection, dogs given 0.25 mg ACTH showed continued elevations in plasma cortisol concentrations at 90 and 120 minutes after ACTH injection. Later, the dogs previously tested with the 1 microgram/kg ACTH challenge were given a single intramuscular dose of prednisone (2.2 mg/kg) and retested with 1 microgram/kg of ACTH one week later. Plasma cortisol levels were significantly reduced after ACTH injection in dogs previously given prednisone demonstrating that a single intramuscular prednisone dose causes detectable adrenocortical suppression one week after administration. The 1 microgram/kg synthetic ACTH challenge test provides a sensitive means for evaluating adrenocortical suppression in dogs.

Neutrophil movement in selected canine skin diseases.

Neutrophilic movement was studied in dogs with atopy, 3 bacterial pyoderma syndromes, flea allergy dermatitis, and generalized demodicosis. Random neutrophil movement was decreased in generalized demodicosis, and this deficit correlated with the extent of body surface skin lesions. Neutrophilic chemotactic movement was decreased in 2 bacterial pyoderma syndromes: bacterial pyoderma, and staphyloccocal pyoderma. Although serum samples from diseased dogs showed no significant differences in chemoattractive qualities from normal pooled canine serum, control canine neutrophils incubated in demodectic dog serum showed decreased chemotactic responsiveness. It was postulated that demodectic dog serum had an inhibitor or deactivator of neutrophil chemotaxis.

Effects of prednisone on thyroid and gonadal endocrine function in dogs.

To assess the effect of a glucocorticoid on thyroid and gonadal endocrine function, prednisone was administered on alternate days to dogs. The prednisone injections resulted in adrenocortical suppression, as shown by the response to ACTH. Basal plasma thyroxine and tri-iodothyronine concentrations were considerably reduced in prednisone-treated dogs. However, the thyroid response to injection of thyrotrophin-releasing hormone was not altered, indirectly demonstrating that pituitary release of TSH was not inhibited by prednisone. Similarly, the response of the thyroid to exogenous TSH was not reduced by prednisone treatment. Electron microscopic examination of thyroid tissue revealed accumulation of colloid droplets in the follicular cell cytoplasm of dogs treated with prednisone. It is postulated that prednisone may interfere with basal thyroid hormone secretion by inhibiting lysosomal hydrolysis of colloid in the thyroid follicular cell. Basal plasma concentrations of LH and testosterone, measured in the male dogs, were reduced by prednisone treatment. Responses of prednisone-treated dogs to luteinizing hormone releasing hormone were not significantly reduced. Prednisone administration did not alter testicular responsiveness to injection of human chorionic gonadotrophin. After orchidectomy, plasma LH values were significantly reduced in prednisone-treated dogs. Taken together, these results suggest that LH secretion in dogs is inhibited at the hypothalamic and/or pituitary level by prednisone administration, which consequently results in reduced testosterone concentrations.

Effects of dexamethasone infusion on the plasma cortisol response to cosyntropin (synthetic ACTH) injection in normal dogs.

Graded dosages of cosyntropin (synthetic corticotropin) were injected into groups of normal dogs on consecutive days. On the first day, cosyntropin was administered alone and, on the second, dogs were infused with dexamethasone three hours before cosyntropin injection. Adrenocortical function was assessed by sequential measurement of plasma cortisol (hydrocortisone) concentration. While no response differences were noted to the various amounts of cosyntropin injected with or without dexamethasone pretreatment, the magnitude of adrenocortical response was significantly greater in dogs infused with dexamethasone. It is concluded that dexamethasone pretreatment renders the canine adrenal cortex more responsive to a subsequent injection of cosyntropin. The combined dexamethasone infusion-cosyntropin injection test produces consistent adrenocortical responses in normal dogs, and has potential value in evaluation of adrenopathic dogs.

Adrenocortical suppression in the dog given a single intramuscular dose of prednisone or triamcinolone acetonide.

Adrenocortical function was assessed in dogs given a single intramuscular dose of either prednisone or triamcinolone acetonide (TCA; or saline solution to controls) to determine the duration of adrenocortical suppression caused by 2 commonly used glucocorticoids. The glucocorticoids were administered at recommended therapeutic doses; therefore, dogs given prednisone received a greater amount of glucocorticoid activity than did in dogs given TCA. Basal and ACTH-stimulated plasma cortisol concentrations, as determined by radioimmunoassay, were obtained once a week. Total intravascular eosinophil concentration and skin responses to intradermally injected histamine phosphate were quantitated. Dogs given TCA showed suppressed basal and ACTH-stimulated plasma cortisol concentrations 1 week after injection; the latter change persisted 2 weeks after injection. Adrenocortical function in 1 of 4 dogs given TCA remained suppressed for 4 weeks. In contrast, prednisone did not significantly alter adrenocortical function. Although intravascular eosinophil concentrations did not vary among groups, skin responses to intradermally injected histamine phosphate were reduced 6 days after prednisone and TCA were given.

Adrenocortical suppression in the dog after a single dose of methylprednisolone acetate.

Adrenal function was assessed in dogs after intramuscular administration of a single dose of methylprednisolone acetate (MPA). Twelve dogs were test challenged with adrenocorticotropic hormone (ACTH) and then assigned randomly to 1 of 3 groups and given MPA. Individual groups were test challenged with ACTH 2, 3, or 4 weeks later. All dogs were rechallenged 5 weeks after MPA administration. Plasma cortisol concentration was determined by radioimmunoassay. Basal plasma cortisol (time 0) was depressed on weeks 2 and 3, but not on weeks 4 and 5. Adrenal response to ACTH (increment of cortisol change) was suppressed on weeks 2, 4, and 5, but not on week 3. It was concluded that a single dose of MPA is capable of altering adrenal cortical function in dogs for at least 5 weeks.

Adrenal gland function in dogs given methylprednisolone.

Serum cortisol (hydrocortisone) was measured by radioimmunoassay in dogs given methylprednisolone (MP) orally or methylprednisolone acetate (MPA) IM. The MP was given on a daily and on an alternate-day basis to different treatment groups and the MPA was administered weekly. Samples of blood were obtained twice a week over a 9-week treatment period for serum cortisol determination, and the adrenal gland response to ACTH was assessed on posttreatment days 1, 3, 5, and 7. Administration of MP on an alternate or daily basis caused a slight but significant (P < 0.05) depression in mean resting cortisol values over time. The MPA administration caused a severe depression of resting serum cortisol values. In response to ACTH, cortisol values invariably increased sharply in nontreated control dogs and in those dogs given MP on an alternate-day basis. Dogs given MP daily had a depressed response to ACTH. The MPA treatment resulted in adrenal cortices that were unresponsive to ACTH. Dogs given MPA, but not challenge exposed with ACTH, had markedly lowered cortisol values for at least 2 weeks after cessation of treatment. Consequently, a difference between daily- and alternate-day MP administration was detected after ACTH challenge exposure; MPA administration inhibited adrenal cortisol secretion for at least the duration of the experiment.

Serum thyroxine content before and after thyrotropin stimulation in dogs with suspected hypothyroidism.

Thyroid function in 39 dogs was studied, utilizing serum thyroxine (T-4) analysis before and 10 hours after thyroid-stimulating hormone (TSH) stimulation. All dogs were treated with pharmacologic doses of L-thyroxine or liothyronine, and the dogs' responses to these treatments were documented. Failure to double control T-4 values after TSH administration was associated with a good response to thyroid medication, whereas a doubling of the control values after TSH administration was associated with negative responses to thyroid medication. Significant difference was not found in the control T-4 values of the various groups, whereas the post-TSH values were significantly different. The study substantiated the value of TSH-response tests in the presumptive diagnosis of canine hypothyroidism.

Disseminated protothecosis with central nervous system involvement in a dog.

A 4-year-old mixed-breed spayed bitch was euthanatized after 2 1/2 months of progressive neurologic disease. Prototheca organisms were identified by histopathology, culture, and electron microscopy. Specific fluorescent antibody procedures revealed two species--Prototheca wickerhamii and Prototheca zopfii. Organisms and pyogranulomatous lesions were found in the brain, spinal cord, right eye, kidneys, and heart.

Hereditary spinal muscular atrophy in Brittany Spaniels: clinical manifestations.

A progressive neurologic disease was identified in a family of closely related Britanny Spaniel dogs. The disease developed in dogs less than 1 year old and characteristically resulted in paraspinal and proximal pelvic limb muscular atrophy. Neurologic examination, electrodiagnostic testing, and histologic studies indicated that the disease results from motor horn cell degeneration. A colony of affected dogs was established, and breeding studies incriminated an inherited basis for the disease.

Myopathy associated with hyperadrenocorticism in the dog.

Naturally occurring or iatrogenic hyperadrenocorticism was associated with myopathy in six dogs. One dog had muscle weakness and muscle atrophy but normal electromyographic findings. Five dogs had muscle stiffness, proximal appendicular muscle enlargement, and myotonic discharges on electromyography. Histologic, electron microscopic, and histochemical findings in the musculature of dogs that were examined were characteristic of noninflammatory degenerative myopathy. Clinical signs of the myopathy improved to varying degrees in five dogs that were treated for the hyperadrenocorticism.

Hereditary canine spinal muscular atrophy.

Hereditary canine spinal muscular atrophy is a newly recognized motor neuron disease occurring in Brittany Spaniels. The clinical manifestations, pattern of inheritance, electrodiagnostic findings, and muscle biopsies have features in common with human spinal muscular atrophy. Neuropathological examination discloses some loss of motor neurons in the spinal cord and brainstem. Many of the surviving motor neurons have neurofibrillary swellings in proximal axons, an abnormality similar to that which occurs early in the course of human amyotrophic lateral sclerosis. These axonal swellings are filled with maloriented skeins of neurofilaments. Since the proteins comprising neurofilaments are carried by slow axonal transport, their accumulation within axons suggest that the swellings may result from impaired slow transport, a hypothesis that can be tested in affected Brittany Spaniels. Hereditary canine spinal muscular atrophy is a new genetic, clinical, and pathological entity, and, at present, it appears to be the best currently available animal model of motor neuron disease.

Atopy.

Atopy should be considered an immunological disorder that may result in several clinical conditions including respiratory disease, allergic dermatitis, food allergy dermatitis, and perhaps flea allergy dermatitis. The clinical course of the disease tends to fluctuate from season to season, which makes objective evaluation of injection therapy difficult. The disease is subject to both familial and environmental influences, and dogs maintain the atopic state throughout their life. The disease cannot be cured; however, a combination of symptomatic and specific injection therapy usually provides adequate control of the clinical signs. Owners of atopic dogs should appreciate that their pet has inherently itching skin, a cure for which is unlikely to be found.