A comparison of two pamidronate dosing protocols on bone turnover in normal dogs and dogs with osteosarcoma

Introduction: Dogs with appendicular osteosarcoma (OSA) excrete higher concentrations of urine cross‐linked N‐telopeptide of type I collagen (NTx) than normal dogs. NTx is a specific biochemical marker of osteoclastic activity. Pamidronate is a bone‐modulating agent that exerts potent inhibitory effects on osteoclasts. The use of pamidronate is currently being evaluated for the management of osteolytic bone pain in dogs with appendicular osteosarcoma. Despite pamidronate's increasing usage in veterinary oncology, optimal dosing has yet to be determined. Commonly utilized dosages range from 1–2 mg/kg, given intravenously (IV) as a 2‐hour constant rate infusion every 28 days. The purpose of this prospective study was to compare the biological activity of two pamidronate doses (1 mg/kg vs. 2 mg/kg) in the suppression of urine NTx excretion in normal dogs and dogs with appendicular osteosarcoma. Methods: Seventeen OSA dogs receiving single‐agent pamidronate as palliative therapy were evaluated. Group 1A (n = 10) received a dose of 1 mg/kg and group 2A (n = 7) received a dose of 2 mg/kg IV. Urine NTx level were measured at day 0 and 28 using a commercial ELISA (Ostex International). Urine NTx level were also measured in 6 normal dogs: Group 1B (n = 3) received a dose of 1 mg/kg and group 2B (n = 3) received a dose of 2 mg/kg. In normal dogs, urine NTx levels were recorded weekly for six consecutive weeks. Results: In dogs with osteosarcoma, greater reductions in urine NTx excretion from baseline values were demonstrated at 2 mg/kg versus 1 mg/kg (57% and 23%, respectively). Likewise, in normal dogs, urine NTx excretion was suppressed to a greater extent with a dosage of 2 mg/kg versus 1 mg/kg (69% and 23%, respectively). Conclusion: Pamidronate possesses biologic activity in both normal dogs and in dogs with osteosarcoma, as assessed by reductions in urine NTx excretion. Based upon reductions in urine NTx excretion, a dosage of 2 mg/kg appears more effective than 1 mg/kg.     

Effects of dexamethasone administration on serum trypsin-like immunoreactivity in healthy dogs

OBJECTIVE: To determine whether administration of dexamethasone altered serum trypsin-like immunoreactivity (TLI) in healthy dogs. ANIMALS: 12 healthy dogs. PROCEDURE: Dexamethasone (0.25 mg/kg, p.o., q 24 h) was administered for 7 days. Serum TLI, alpha-amylase and alanine aminotransferase (ALT) activities, and urea and creatinine concentrations were determined on days 0, 7, 14, and 21 of the study. RESULTS: Serum TLI and ALT activities were significantly increased, and serum alpha-amylase activity was significantly decreased after administration of dexamethasone for 7 days. However, values obtained on days 14 and 21 were not significantly different from baseline values. Dexamethasone administration was not associated with any significant changes in serum creatinine or urea concentrations. Serum TLI and alpha-amylase activities were significantly correlated prior to dexamethasone administration. Dogs did not develop clinical signs of pancreatitis. CONCLUSIONS AND CLINICAL RELEVANCE: Dexamethasone administration was associated with an increase in serum TLI. However, values returned to baseline 7 days after dexamethasone administration was discontinued. Serum TLI may be falsely high in dogs that have been treated with dexamethasone in the week preceding analysis.     

Effect of benazepril and pimobendan on serum angiotensin‐converting enzyme activity in dogs

To support their combined use, the objective of the study was to evaluate the effects of benazepril and pimobendan on serum angiotensin‐converting enzyme (ACE) activity in dogs. A total of 48 healthy beagle dogs were randomized into four groups (n = 12 per group) in a parallel‐group design study: A (control, placebo twice daily (BID)); B (0.5–1.0 mg/kg benazepril once daily (SID) in the morning, placebo in the evening); C (0.25–0.5 mg/kg benazepril BID); D (0.25–0.5 mg/kg benazepril and 0.125–0.25 mg/kg pimobendan, both BID). The test items were administered orally for 15 days. Serum ACE activity was measured on days 1 and 15. Groups B, C and D had significantly lower average serum ACE activity compared to baseline and to the control group, on both days 1 and 15. There were no significant differences in average ACE activity between groups B, C and D. Noninferiority of group C to B was demonstrated. In conclusion, 0.25–0.5 mg/kg benazepril administered BID produced noninferior inhibition of serum ACE activity compared to 0.5–1.0 mg/kg benazepril dosed SID. Pimobendan had no significant effect on benazepril's action on serum ACE activity. The results support the use of benazepril BID in dogs and in combination with pimobendan.     

Retrospective assessment of tolerability and efficacy of zoledronate in the palliative treatment of cancer-bearing dogs

Zoledronate is a bisphosphonate frequently used for the treatment of hypercalcaemia of malignancy and tumour-associated bone pain in dogs, however, there is a paucity of information regarding its use in veterinary medicine. The aim of this retrospective study was to report the tolerability of zoledronate in the palliative treatment of cancer-bearing dogs and secondarily to to assess the efficacy of zoledronate for the treatment of hypercalcaemia of malignancy. Thirty-seven dogs (22 with tumour-associated bone pain and 15 with hypercalcaemia of malignancy) that received 114 zoledronate infusions were included. Tolerability was assessed by the absence of post-zoledronate hypocalcaemia or other adverse events as defined by Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events criteria. Efficacy was assessed by comparison of available ionized calcium levels before and after zoledronate administration in hypercalcaemic dogs. In 79% of zoledronate infusions, no adverse events were reported. The majority of adverse events which occurred in the other 21% of infusions could be attributed to concurrent chemotherapy or the underlying neoplastic disease. There was a small but significant increase in creatinine following treatment with zoledronate, however, none of the dogs developed clinically significant renal disease. In eight hypercalcaemic dogs with available ionized calcium following zoledronate administration, ionized calcium decreased rapidly within 7 days following treatment with zoledronate. Zoledronate is well-tolerated with few recorded adverse events, however, monitoring of serum creatinine is advised. Zoledronate seems to be effective in the treatment of hypercalcaemia of malignancy.     

Faecal calcium excretion does not decrease during long‐term feeding of a low‐calcium diet in adult dogs

According to a previous meta‐analysis, adult dogs do not notably increase calcium absorption from the gastrointestinal tract when calcium intake is decreased. This results in a negative calcium balance even with a moderate calcium reduction. In this study we wanted to verify (i) whether a negative calcium balance occurs at a calcium intake equivalent to NRC (2006) (Nutrient requirements of dogs and cats, 2006, The National Academies Press, Washington, DC) minimal requirements, and if so (ii) whether the negative calcium balance will persist for up to 6 months on a low‐calcium diet. After a pre‐feeding period of at least 18 weeks with calcium intake slightly exceeding maintenance requirements (200 mg/kg body weight^0.75), 12 dogs (6 Beagles, 6 Foxhound crossbreds) were fed a low‐calcium diet for 28 weeks. One dog was removed from the trial for reasons unrelated to the study at week 23. Calcium intake amounted to 60 mg/kg body weight^0.75 corresponding to the minimal requirement for maintenance in dogs (NRC, 2006 (Nutrient requirements of dogs and cats, 2006, The National Academies Press, Washington, DC)). Digestion trials were carried out at week 7, 14, 21 and 28 of the low calcium feeding period. At these time points, and at week 18 of the pre‐trial, blood samples were taken and analysed for calcium, ionised calcium, phosphorus, parathyroid hormone, vitamin D, serum crosslaps and bone alkaline phosphatase. Apparent calcium digestibility was negative throughout the study, suggesting a negative calcium balance. There was no systematic decrease in faecal calcium excretion. Serum calcium, ionised calcium and phosphorus remained within the reference range. Serum crosslaps increased continuously from baseline to week 28 of trial, with averages increasing from 0.102 ng/ml to 0.279 ng/ml, suggesting osteoclastic activity, indicative of calcium mobilisation from the skeleton. The study supports the theory of a lack of adaptation of intestinal calcium absorption from diets with relatively low calcium content in dogs. This agrees with clinical findings in dogs eating low‐calcium diet.     

The bone biologic effects of zoledronate in healthy dogs and dogs with malignant osteolysis

BACKGROUND: Malignant osteolysis is a process whereby cancer cells in concert with osteoclasts erode bone matrix. Aminobisphosphonates (NBPs) such as zoledronate induce osteoclast apoptosis and thereby decrease malignant skeletal destruction, severity of bone pain, and frequency of pathologic fracture. HYPOTHESIS: IV-administered zoledronate will reduce homeostatic bone turnover in healthy dogs and pathologic bone resorption in dogs diagnosed with primary and secondary bone tumors. ANIMALS: Six healthy dogs and 20 dogs with naturally occurring primary or metastatic bone tumors were administered zoledronate IV. METHODS: Prospective study: In all dogs, healthy (n = 6) and with malignant osteolysis (n = 20), the bone biologic effects of zoledronate were evaluated by quantifying changes in serum C-telopeptide (CTx) or urine N-telopeptide (NTx) concentrations or both. In dogs with osteosarcoma (OSA) (n = 10), serial changes in tumor relative bone mineral density (rBMD) assessed by dual-energy x-ray absorptiometry were used to characterize zoledronate's antiresorptive effects within the immediate tumor microenvironment. Additionally, the biochemical tolerability of zoledronate was assessed in 9 dogs receiving multiple (> or =2) consecutive treatments. RESULTS: All dogs had significant reductions in serum CTx or urine NTx concentrations or both after zoledronate administration. In a subset of dogs with appendicular OSA, reduced urine NTx concentrations and increased primary tumor rBMD coincided with improved limb usage as reported by pet owners in dogs treated with zoledronate and concurrent oral analgesics. Multiple zoledronate infusions were not associated with biochemical evidence of toxicosis. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with skeletal neoplasms, IV-administered zoledronate exerts bone biologic effects, appears safe, and can provide pain relief.     

Duration of increased serum alkaline phosphatase activity in dogs receiving different glucocorticoid doses

Exposure to exogenous glucocorticoids can variably increase the serum alkaline phosphatase (alp) activity, however, the duration of this effect in dogs has not been determined. In this study, three groups of ten clinically normal adult dogs were administered different types of glucocorticoids at therapeutic doses. Group 1 received prednisone 1 mg kg day(-1)p.o. for 3 weeks; Group 2 received a single dose of methylprednisone acetate 1.1 mg kg day(-1)s.c.; Group 3 received dexamethasone 0.25 mg kg day(-1)p.o. for 1 week. In Group 1 elevations were statistically significant on days 7, 14 and 21 (P<0.01, P<0.001, P<0.001, respectively). After discontinuing therapy serum alp returned to baseline levels in 7 days. In Group 2, serum alp activity remained significantly elevated for 3 weeks after therapy (P<0.05, P<0.001, P<0.01 on days 7, 14 and 21 respectively). In Group 3, serum alp levels were significantly increased after 1 week of therapy (P<0.001) returning to basal levels 2 weeks after discontinuing glucocorticoid administration. In conclusion, duration of increased serum alp activity was variable and with the protocols assessed a 3-week period for short-acting glucocorticoids and more than 4 weeks for long-acting methylprednisone may be required to return to baseline levels in all dogs.     

Effects of chlorothiazide on urinary excretion of calcium in clinically normal dogs.

Administration of thiazide diuretics has been recommended to prevent calcium oxalate urolith development in dogs. To evaluate the effects of thiazide diuretics in dogs, 24-hour urine excretion of calcium was measured in 6 clinically normal Beagles after administration of chlorothiazide (CTZ) for 2 weeks, administration of CTZ for 10 weeks, and administration of calcium carbonate and CTZ for 2 weeks. Compared with baseline values, 24-hour urine calcium excretion did not decrease after CTZ administration. When CTZ was given at a high dosage (130 mg/kg of body weight), urinary calcium excretion was significantly (P < 0.04) higher than baseline values. Based on these observations, we do not recommend CTZ for treatment or prevention of canine calcium oxalate urolithiasis.     

Effects of zoledronate on markers of bone metabolism and subchondral bone mineral density in dogs with experimentally induced cruciate-deficient osteoarthritis

OBJECTIVE: To evaluate effects of zoledronate on markers of bone metabolism in dogs after transection of the cranial cruciate ligament (CrCL). ANIMALS: 21 adult dogs. PROCEDURE: Unilateral CrCL transection was performed arthroscopically. Dogs were allocated to 3 groups (control group, low-dose zoledronate [10 microg/kg, SC, q 90 d for 12 months], and high-dose zoledronate [25 microg/kg, SC, q 90 d for 12 months]). Serum osteocalcin (OC), serum bone-specific alkaline phosphatase (BAP), and urine pyridinoline and deoxypyridinoline concentrations were measured at 0, 1, 3, 6, 9, and 12 months after surgery. Bone mineral density (BMD) was determined in the distal portion of the femur and proximal portion of the tibia via computed tomography at each time point. Data were analyzed by a repeated-measures ANOVA. RESULTS: oledronate inhibited OC in the high-dose group at 9 and 12 months and at 12 months in the low-dose group, compared with the control group. High-dose zoledronate decreased BAP concentrations 3 and 9 months after surgery. In the control group, BMD was decreased in the femoral condyle and caudal tibial plateau. Zoledronate prevented significant BMD decreases starting 1 month after transection, compared with control dogs. In the caudomedial aspect of the tibial plateau, both zoledronate groups had significant increases in BMD after 3 months, compared with control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Zoledronate may reduce subchondral bone loss and effect markers of bone metabolism in dogs with experimentally induced instability of the stifle joint and subsequent development of osteoarthritis.     

Effect of cisplatin on bone transport osteogenesis in dogs

OBJECTIVE: To document effects of cisplatin on regenerate bone formation during the distraction and consolidation phases of bone transport osteogenesis. ANIMALS: 10 skeletally mature hounds. PROCEDURES: Bone transport osteogenesis was performed to reconstruct a 3-cm defect in the radius of each dog. Five dogs were randomly selected to receive cisplatin (70 mg/m2, IV, q 21 d for 4 cycles), and 5 were administered saline (0.9% NaCl) solution. Bone mineral density was measured by use of dual-energy x-ray absorptiometry (DEXA) on days 24, 55, and 90 after surgery. Dogs were euthanatized 90 days after surgery. Histomorphometry was performed on nondecalcified sections of regenerate bone. Bone mineral density and histomorphometric indices of newly formed bone were compared between groups. RESULTS: Densitometric differences in regenerate bone mineral density were not detected between groups at any time period. Cisplatin-treated dogs had decreased mineralized bone volume, decreased percentage of woven bone volume, decreased percentage of osteoblast-covered bone, increased porosity, and increased percentage of osteoblast-covered surfaces, compared with values for control dogs. Lamellar bone volume and osteoid volume did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Regenerate bone will form and remodel during administration of cisplatin. Results of histomorphometric analysis suggest that bone formation and resorption may be uncoupled in cisplatin-treated regenerate bone as a result of increased osteoclast activity or delayed secondary bone formation during remodeling. These histomorphometric differences were modest in magnitude and did not result in clinically observable complications or decreased bone mineral density as measured by use of DEXA.     

Urine N-telopeptide excretion in dogs with appendicular osteosarcoma

Canine appendicular osteosarcoma (OSA) is a commonly diagnosed cancer that is capable of inducing pathologic bone remodeling. Investigating surrogate indices of bone metabolism may contribute to the diagnostic and therapeutic management of bone malignancies in companion animals. This study evaluated the excretion of N-terminal telopeptide (NTx), a marker of bone resorption that is detected in urine. Sixty-three dogs with appendicular OSA were compared with 29 age-matched healthy dogs. Dogs with appendicular OSA had significantly higher baseline urine NTx excretion than healthy controls (P < .0001). In 17 dogs with OSA treated with either amputation or standardized palliative therapies, significant reductions in urine NTx excretion were observed, suggesting that excessive bone resorption in dogs with OSA may be linked with focal skeletal osteolysis or its consequences. To identify any relationship between indicators of pathologic bone turnover, baseline urine NTx excretion was correlated with serum bone alkaline phosphatase (bALP) or radiographic tumor lengths at diagnosis. No significant correlations were identified between baseline urine NTx excretion and either bALP or tumor length. The findings from this study suggest that high urinary NTx excretion may support the diagnosis of focal skeletal osteolysis in dogs, and reductions in urine NTx excretion after treatment may reflect elimination or minimization of pathologic bone resorption.     

Effect of chronic lead exposure on the canine bone marrow

The effect of chronic oral led acetate administration on canine bone marrow was studied. Two dogs (group 1) were used as controls, 4 dogs (group 2) were given 2 mg of lead/kg of body weight daily, and 4 dogs (group 3) were given 5 mg of lead/kg daily. After a 7-day stabilizaion period, lead dosing was conducted for 91 days (13 weeks), after which half of each group was treated with calcium ethylenediaminetetraacetic acid. All dogs were then observed for another 28 days (4 weeks). Blood lead values and bone marrow cellular changes were monitored once a week during the 126 days (18 weeks) of study. Lead-dosed dogs had lower weight gains than the controls. Clinical signs of toxicosis were observed after 6 weeks in one dog in group 3. Anorexia, body weight loss, CNS depression, muscular weakness, and trembling were seen. Blood lead concentrations increased in all group 2 and 3 dogs. Lead caused increases in bone marrow segmented neutrophils and myeloid series cells, and increased myeloid:erythroid ratios. Blood lead concentrations and myeloid:erythroid ratios decreased after cessation of lead administration.     

Urinary corticoids in the diagnosis of canine hyperadrenocorticism

In 20 healthy experimental dogs the 24 hour urinary corticoid excretion as measured by cortisol radioimmunoassay on two consecutive days varied from 0.5 to 3.3 nmol/kg/24 hours and from 0.3 to 3.6 nmol/kg/24 hours. In 20 dogs with otherwise proven spontaneous hyperadrenocorticism these values varied from 4.4 to 35.7 nmol/kg/24 hours and from 3.6 to 26.8 nmol/kg/24 hours respectively. Corticoid/creatinine ratios in morning urine samples of 28 healthy pet dogs were 1.2 to 6.9 X 10(-6). In 27 dogs with spontaneous hyperadrenocorticism all ratios exceeded the range observed in the healthy pet dogs.     

Effects of Glucocorticoid Therapy on Urine Protein-to-Creatinine Ratios and Renal Morphology in Dogs

Glomerulonephritis has been associated with exogenous glucocorticoid administration and spontaneous hyperadrenocorticism in the dog. The purpose of this study was to determine the effects of long-term glucocorticoid therapy on urine protein:creatinine ratios (UP/Cs) and renal morphology. Nine young-adult male dogs were determined to be healthy and have normal renal function as assessed by physical examination, CBC, serum biochemistry analysis, Knott's test for Dirofilaria immitis , urinaly-sis, urine culture, urine protein electrophoresis, endogenous creatinine clearance, 24-hour urinary protein excretion, and UP/C. Prednisone was administered to each dog at a dosage of 2.2 mg/kg PO bid for 42 days. Urinalysis and UP/C were performed on days 0, 7, 14, 21, 28, and 42 of treatment. Mean UP/C on day 0 was 0.29 ± 0.10. Mean UP/C increased progressively to a maximum of 1.27 ± 1.02 on day 28. Mean UP/C on day 42 decreased slightly (0.92 ± 0.56) but remained significantly increased above baseline.
The most consistent renal light microscopic finding on necropsy examination was generalized hypercellular glomerular tufts, suggestive of mesangial cell proliferation. Four dogs also had occasional adhesions of glomerular tufts to Bowman's capsule, accompanied by thickening of the capsule. Direct immunofluorescence for immunoglobulin deposition was negative in all dogs. Electron microscopy, evaluated in 7 dogs, was characterized by occasional mild segmental thickening of basement membranes, fusion of visceral cell foot processes, and glomerular adhesions. The results of this study indicate that long-term administration of glucocorticoids results in significant proteinuria and glomerular changes in the dog.     

Effect of an anti-inflammatory dose of prednisone on thyroid hormone monitoring in hypothyroid dogs

It is not uncommon for a hypothyroid dog to be receiving concurrent corticosteroids. As hypothyroid dogs receiving thyroid supplement need periodic monitoring, knowledge of whether prednisone alters thyroid hormone concentrations would be useful to determine whether testing can or should be done while the dog is receiving therapy and whether dose adjustments are appropriate. In this study, the effect of short-term anti-inflammatory prednisone was determined in dogs with naturally occurring hypothyroidism. Eight adult dogs were given prednisone (1.0 mg/kg, orally) daily for 7 days and then on alternate days for 14 days. Serum total thyroxine (T(4) ), free T(4) (fT(4) ), and thyroid-stimulating hormone (TSH) were measured on days 7, 21 and 28 and compared with baseline data. Total T(4) concentrations were significantly decreased after 7 days of anti-inflammatory prednisone, but were not significantly altered from baseline on days 21 or 28. Free T(4) and TSH concentrations were not significantly altered from baseline at any point during the study. Two dogs had decreased total T(4) concentrations on day 7, which may have resulted in an alteration in thyroid supplementation. Results showed that administration of prednisone at a dosage of 1 mg/kg, orally, once daily for 7 days decreased total T(4) , while fT(4) was unchanged, suggesting that fT(4) may be less affected by daily prednisone administration. Anti-inflammatory doses of prednisone administered every other day did not interfere with thyroid hormone monitoring.     

Efficacy of milbemycin oxime against naturally acquired or experimentally induced Ancylostoma spp and Trichuris vulpis infections in dogs.

The efficacy of milbemycin oxime was evaluated at dosages of 0.25, 0.50, and 0.75 mg/kg of body weight in dogs naturally infected with mature Ancylostoma spp, at a dosage of 0.50 mg/kg in dogs with experimentally induced immature and mature A caninum, and at dosages of 0.55 to 0.86 mg/kg in dogs naturally infected with mature Trichuris vulpis. Milbemycin oxime was 95 and 99% effective against mature Ancylostoma spp at dosages of 0.50 and 0.75 mg/kg, respectively, but only 49% effective at a dosage of 0.25 mg/kg. Efficacy was 49% against pulmonary L3-L4 stages of A caninum (36 hours after inoculation), greater than 80% against L4 (120 hours after inoculation) and early L5 stages (216 hours after inoculation), and greater than 90% against experimentally induced mature stages (360 hours after inoculation). Milbemycin oxime was also 97% effective in the removal of mature Tr vulpis from naturally infected dogs. Adverse reactions were not observed following treatment in any of the dogs.     

Evaluation of intravenous pamidronate administration in 33 cancer-bearing dogs with primary or secondary bone involvement

The purpose of this study was to evaluate the clinical safety of pamidronate when administered at a mean dosage of 1.0 mg/kg IV q28d in 33 tumor-bearing dogs. Biochemical tests of renal function were evaluated before each successive pamidronate treatment. Of 33 dogs treated with pamidronate, 1 dog had clinically relevant increases in serum creatinine and blood urea nitrogen concentrations. The biologic activity of IV pamidronate was assessed prospectively in 10 dogs with appendicular osteosarcoma and was assessed on reductions in urine N-telopeptide excretion (P = .042) and enhanced bone mineral density of the primary tumor measured with dual-energy x-ray absorptiometry (P = .024). Additionally, in these 10 dogs, pamidronate's therapeutic activity was supported by subjective improvement in pain control in 4 of the 10 dogs treated. IV pamidronate appears clinically safe in tumor-bearing dogs and may possess modest biologic activity for managing neoplastic complications associated with pathologic bone resorption.     

Use of ambulatory electrocardiography for detection of ventricular premature complexes in healthy dogs

OBJECTIVE: To evaluate the use of 24-hour ambulatory electrocardiography (AECG) for the detection of ventricular premature complexes (VPC) in healthy dogs. DESIGN: Case series. ANIMALS: 50 healthy mature dogs. PROCEDURE: A 24-hour AECG was performed on each dog and evaluated for the presence of VPC. RESULTS: Fifty dogs weighing between 18.2 to 40.9 kg (40 and 90 lb) representing 13 breeds were evaluated; there were 4 sexually intact females, 21 spayed females, 4 sexually intact males, and 21 castrated males. Ages ranged from 1 to 12 years. Thirty-four dogs had no VPC; 16 dogs had between 1 and 24 VPC. The grade of arrhythmia ranged from 1 to 4, with 4 dogs having an arrhythmia with a grade > 1. Significant differences were not detected between the group of dogs with VPC and those without VPC with regard to sex, age, and minimum, maximum, or mean heart rate. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that healthy mature dogs have infrequent VPC, as detected by use of 24-hour AECG. The presence of numerous or sequential VPC may be suggestive of cardiac or systemic disease and may indicate the need for thorough clinical evaluation.     

Effects of oral administration of controlled-ileal-release budesonide and assessment of pituitary-adrenocortical axis suppression in clinically normal dogs

OBJECTIVE: To evaluate the effects of oral administration of controlled-ileal-release (CIR) budesonide on the pituitary-adrenal axis in dogs with a normal gastrointestinal mucosal barrier. ANIMALS: 10 healthy dogs. PROCEDURES: 5 dogs received CIR budesonide orally once daily for days 1 through 28, and 5 dogs received placebo. Treatment group dogs that weighed < 18 kg received 2 mg of CIR budesonide; treatment group dogs that weighed > or = 18 kg received 3 mg of CIR budesonide. In the treatment and placebo groups, there were 3 and 2 dogs, respectively, that weighed > 18 kg. Plasma cortisol concentration before and after ACTH stimulation, basal plasma endogenous ACTH concentration, and body weight were measured on days 0, 7, 14, 21, 28, and 35. Serum biochemical analysis, CBC determination, and urinalysis were performed on days 0, 28, and 35. On days 7, 14, and 21, serum ALP and ALT activities, serum glucose concentration, and urine specific gravity were obtained in lieu of a full hematologic evaluation and urinalysis. RESULTS: Basal and post-ACTH stimulation plasma cortisol concentrations and plasma endogenous ACTH concentration were significantly suppressed by treatment. No other variables were altered over the course of the study. CONCLUSIONS AND CLINICAL RELEVANCE: Budesonide suppresses pituitary-adrenal function in dogs with normal gastrointestinal integrity, whereas other variables often affected by glucocorticoids were not altered by a 4-week treatment course. Budesonide may be a good alternative to traditional cortico-steroids if used short-term for acute exacerbations of inflammatory bowel disease.