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Objective: To determine the change in mean hepatic apparent diffusion coefficient (ADC) and hepatic fat fraction (HFF) during body weight gain in cats by use of MRI., Animals: 12 purpose-bred adult neutered male cats., Procedures: The cats underwent general health and MRI examination at time 0 (before dietary intervention) and time 1 (after 40 weeks of being fed high-energy food ad libitum). Sequences included multiple-echo gradient-recalled echo MRI and diffusion-weighted MRI with 3 b values (0, 400, and 800 s/mm 2 ). Variables (body weight and the HFF and ADC in selected regions of interest in the liver parenchyma) were compared between time points by Wilcoxon paired-sample tests. Relationships among variables were assessed with generalized mixed-effects models., Results: Median body weight was 4.5 and 6.5 kg, mean ± SD HFF was 3.39 ± 0.89% and 5.37 ± 1.92%, and mean ± SD hepatic ADC was 1.21 ± 0.08 × 10 -3 mm 2 /s and 1.01 ± 0.2 × 10 -3 mm 2 /s at times 0 and 1, respectively. Significant differences between time points were found for body weight, HFF, and ADC. The HFF was positively associated with body weight and ADC was negatively associated with HFF., Conclusions and Clinical Relevance: Similar to findings in people, cats had decreasing hepatic ADC as HFF increased. Protons associated with fat tissue in the liver may reduce diffusivity, resulting in a lower ADC than in liver with lower HFF. Longer studies and evaluation of cats with different nutritional states are necessary to further investigate these findings.

OBJECTIVE To describe perfusion and diffusion characteristics of the liver, spleen, and kidneys of healthy adult male cats as determined by morphological, perfusion-weighted, and diffusion-weighted MRI. ANIMALS 12 healthy adult male cats. PROCEDURES Each cat was anesthetized. Morphological, perfusion-weighted, and diffusion-weighted MRI of the cranial aspect of the abdomen was performed. A region of interest (ROI) was established on MRI images for each of the following structures: liver, spleen, cortex and medulla of both kidneys, and skeletal muscle. Signal intensity was determined, and a time-intensity curve was generated for each ROI. The apparent diffusion coefficient (ADC) was calculated for the hepatic and splenic parenchyma and kidneys on diffusion-weighted MRI images. The normalized ADC for the liver was calculated as the ratio of the ADC for the hepatic parenchyma to the ADC for the splenic parenchyma. RESULTS Perfusion-weighted MRI variables differed among the 5 ROIs. Median ADC of the hepatic parenchyma was 1.38 × 10 -3 mm 2 /s, and mean ± SD normalized ADC for the liver was 1.86 ± 0.18. Median ADC of the renal cortex and renal medulla was 1.65 × 10 -3 mm 2 /s and 1.93 × 10 -3 mm 2 /s, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results provided preliminary baseline information about the diffusion and perfusion characteristics of structures in the cranial aspect of the abdomen of healthy adult male cats. Additional studies of cats of different sex and age groups as well as with and without cranial abdominal pathological conditions are necessary to validate and refine these findings.

Objective: To assess the effects of 3 contrast medium injection techniques on attenuation values for canine adrenal glands during contrast-enhanced CT., Animals: 9 healthy Beagles., Procedures: 3 protocols were evaluated in a randomized cross-over design study: 700 mg of iodine/kg at a constant injection rate over 20 seconds (full-dose constant rate), the same dose at a rate following an exponential decay curve over 20 seconds (full-dose decelerated rate), and 350 mg of iodine/kg at a constant injection rate over 10 seconds (half-dose constant rate). Multislice CT images were obtained before and at predetermined time points after the start of contrast medium injection., Results: Median peak attenuation values were 129, 133, and 87 Hounsfield units with the full-dose constant rate, full-dose decelerated rate, and half-dose constant rate injection protocols, respectively. Peak attenuation differed significantly between the full-dose constant rate and half-dose constant rate injection protocols and between the full-dose decelerated rate and half-dose constant rate injection protocols. Median time to peak attenuation did not differ significantly among injection methods and was 30, 23, and 15 seconds for the full-dose constant rate, full-dose decelerated rate, and half-dose constant rate injections, respectively., Conclusions and Clinical Relevance: The dose of contrast medium and the timing of postinjection CT scanning were main determinants of peak attenuation for adrenal glands in healthy dogs; effects of the 3 injection protocols on attenuation were minor. The exponentially decelerated injection method was subjectively complex. A constant injection protocol delivering 700 mg of iodine/kg over 20 seconds, with scans obtained approximately 30 seconds after starting contrast medium injection, provided images with maximum adrenal gland attenuation values.

Objective: To evaluate the effects of cisapride and metoclopramide hydrochloride administered orally on the lower esophageal sphincter (LES) resting pressure in awake healthy dogs., Animals: 6 adult Beagles., Procedures: Each dog was evaluated after administration of a single dose of cisapride (0.5 mg/kg), metoclopramide (0.5 mg/kg), or placebo (empty gelatin-free capsule) in 3 experiments performed at 3-week intervals. To measure LES pressure, a high-resolution manometry catheter equipped with 40 pressure sensors spaced 10 mm apart was used. For each experiment, LES pressure was recorded during a 20-minute period with a virtual electronic sleeve emulation before treatment (baseline) and at 1, 4, and 7 hours after drug or placebo administration. A linear mixed-effects model was used to test whether the 3 treatments affected LES pressure differently., Results: In the cisapride, metoclopramide, and placebo experiments, median baseline LES pressures were 29.1, 30.5, and 29.0 mm Hg, respectively. For the cisapride, metoclopramide, and placebo treatments, median LES pressures at 1 hour after administration were 44.4, 37.8, and 36.6 mm Hg, respectively; median LES pressures at 4 hours after administration were 50.7, 30.6, and 31.1 mm Hg, respectively; and median LES pressures at 7 hours after administration were 44.3, 28.5, and 33.3 mm Hg, respectively. The LES pressures differed significantly only between the placebo and cisapride treatments., Conclusions and Clinical Relevance: Results suggested that orally administered cisapride may be of benefit in canine patients for which an increase in LES pressure is desirable, whereas orally administered metoclopramide did not affect LES resting pressures in dogs.

Objective: To evaluate the use of high-resolution manometry (HRM) in awake and sedated dogs and to assess potential effects of a standard sedation protocol., Animals: 22 Beagles., Procedures: An HRM catheter with 36 pressure sensors was inserted intranasally in each dog. After an adaption period of 5 minutes, each set of measurements included 5 swallows of a liquid and 5 swallows of a solid bolus. Measurements were repeated 30 minutes after IM administration of buprenorphine and acepromazine., Results: HRM was successfully performed in 14 dogs. Data sets of 8 dogs were adequate for analysis. For the upper esophageal sphincter, median values of baseline pressure, residual pressure, relaxation time to nadir, and relaxation duration were determined for awake and sedated dogs for liquid and solid swallows. For the tubular portion of the esophagus, median values of peristaltic contractile integral, bolus transit time, and contractile front velocity were determined for awake and sedated dogs for liquid and solid swallows. For the lower esophageal sphincter, median values of baseline pressure and residual pressure were determined for awake and sedated dogs for liquid and solid swallows. Significant differences (awake vs sedated) were found for the upper esophageal sphincter residual pressure (liquid swallows), relaxation time to nadir (liquid swallows), bolus transit time (solid swallows), and contractile front velocity (solid swallows)., Conclusions and Clinical Relevance: HRM was feasible for evaluation of esophageal function in most awake dogs. Although sedation in uncooperative patients may minimally influence results of some variables, an overall assessment of swallowing should be possible.

Objective: To evaluate 4 methods used to measure plasma insulin-like growth factor (IGF) 1 concentrations in healthy cats and cats with diabetes mellitus or other diseases., Animals: 39 healthy cats, 7 cats with diabetes mellitus, and 33 cats with other diseases., Procedures: 4 assays preceded by different sample preparation methods were evaluated, including acid chromatography followed by radioimmunoassay (AC-RIA), acid-ethanol extraction followed by immunoradiometry assay (AEE-IRMA), acidification followed by immunochemiluminescence assay (A-ICMA), and IGF-2 excess followed by RIA (IE-RIA). Validation of the methods included determination of precision, accuracy, and recovery. The concentration of IGF-1 was measured with all methods, and results were compared among cat groups., Results: The intra-assay coefficient of variation was < 10% for AC-RIA, A-ICMA, and AEE-IRMA and 14% to 22% for IE-RIA. The linearity of dilution was close to 1 for each method. Recovery rates ranged from 69% to 119%. Five healthy cats had IGF-1 concentrations > 1,000 ng/mL with the AEE-IRMA, but < 1,000 ng/mL with the other methods. Compared with healthy cats, hyperthyroid cats had significantly higher concentrations of IGF-1 with the A-ICMA method, but lower concentrations with the IE-RIA method. Cats with lymphoma had lower IGF-1 concentrations than did healthy cats regardless of the method used., Conclusions and Clinical Relevance: Differences in the methodologies of assays for IGF-1 may explain, at least in part, the conflicting results previously reported in diabetic cats. Disorders such as hyperthyroidism and lymphoma affected IGF-1 concentrations, making interpretation of results more difficult if these conditions are present in cats with diabetes mellitus.

Objective: To determine reference ranges for serum cobalamin (Cbl), urine methylmalonic acid (uMMA), and plasma total homocysteine (tHcys) concentrations and to compare values for healthy control dogs with values for Border Collies (BCs), a breed in which hereditary cobalamin deficiency has been identified., Animals: 113 BCs, 35 healthy control dogs fed a typical diet, and 12 healthy dogs fed a bone and raw food diet exclusively., Procedures: Urine and blood samples were obtained from each dog and Cbl, uMMA, and tHcys concentrations were determined., Results: Reference ranges for Cbl (261 to 1,001 ng/L), uMMA (0 to 4.2 mmol/mol of creatinine), and tHcys (4.3 to 18.4 μmol/L) concentrations were determined. Four BCs had a Cbl concentration lower than the assay detection limit (150 ng/L); median uMMA and tHcys concentrations in these dogs were 4,064 mmol/mol of creatinine and 51.5 μmol/L, respectively. Clinical abnormalities included stunted growth, lethargy, anemia, and proteinuria. Abnormalities improved after administration of cobalamin. Of the 109 healthy BCs with Cbl and tHcys concentrations within reference ranges, 41 (37.6%) had a high uMMA concentration (range, 5 to 360 mmol/mol). Results for dogs fed raw food were similar to those for control dogs., Conclusions and Clinical Relevance: Hereditary cobalamin deficiency is a rare disease with various clinical signs. The finding of methylmalonic aciduria in healthy eucobalaminemic BCs and BCs with clinical signs of Cbl deficiency was surprising and indicated these dogs may have defects in intracellular processing of Cbl or intestinal Cbl malabsorption, respectively. Studies investigating Cbl absorption and metabolic pathways are warranted.

Objective: To investigate the effects of twice-daily oral administration of hydrocortisone on the bile acids composition of gallbladder bile in dogs., Animals: 6 placebo-treated control dogs and 6 hydrocortisone-treated dogs., Procedures: Dogs received hydrocortisone (median dose, 8.5 mg/kg) or a gelatin capsule (control group) orally every 12 hours for 84 days. Gallbladder bile samples were obtained via percutaneous ultrasound-guided cholecystocentesis from each dog before (day 0 [baseline]), during (days 28, 56, and 84), and after (days 28p, 56p, and 84p) treatment for differentiated quantification of unconjugated bile acids and taurine-conjugated and glycine-conjugated bile acids via high-performance liquid chromatography-tandem mass spectrometry., Results: Treatment with hydrocortisone for 84 days resulted in significant and reversible increases in the concentrations of unconjugated bile acids (ie, cholic, chenodeoxycholic, and deoxycholic acids) and a significant and reversible decrease in the concentration of total taurine-conjugated bile acids, compared with baseline or control group values. Treatment with hydrocortisone had no effect on bile concentrations of glycine-conjugated bile acids., Conclusions and Clinical Relevance: In dogs, hydrocortisone administration caused reversible shifts toward higher concentrations of the more hydrophobic unconjugated bile acids (chenodeoxycholic acid and deoxycholic acid) and toward lower concentrations of the amphipathic taurine-conjugated bile acids in gallbladder bile. These data suggest that similar bile acids changes could cause major alterations in gallbladder structure or function over time in hypercortisolemic dogs.

Objective: To evaluate the use of recombinant human (rh) thyroid-stimulating hormone (TSH) in dogs with suspected hypothyroidism., Animals: 64 dogs with clinical signs of hypothyroidism., Procedures: Dogs received rhTSH (75 microg/dog, IV) at a dose independent of their body weight. Blood samples were taken before and 6 hours after rhTSH administration for determination of total serum thyroxine (T(4)) concentration. Dogs were placed into 1 of 3 groups as follows: those with normal (ie, poststimulation values indicative of euthyroidism), unchanged (ie, poststimulation values indicative of hypothyroidism; no thyroid gland stimulation), or intermediate (ie, poststimulation values between unchanged and normal values) post-TSH T(4) concentrations. Serum canine TSH (cTSH) concentration was determined in prestimulation serum (ie, before TSH administration)., Results: 14, 35, and 15 dogs had unchanged, normal, and intermediate post-TSH T(4) concentrations, respectively. Basal T(4) and post-TSH T(4) concentrations were significantly different among groups. On the basis of basal serum T(4) and cTSH concentrations alone, 1 euthyroid (normal post-TSH T(4), low basal T(4), and high cTSH concentrations) and 1 hypothyroid dog (unchanged post-TSH T(4) concentration and low to with-in reference range T(4) and cTSH concentrations) would have been misinterpreted as hypothyroid and euthyroid, respectively. Nine of the 15 dogs with intermediate post-TSHT(4) concentrations had received medication known to affect thyroid function prior to the test, and 2 of them had severe nonthyroidal disease., Conclusions and Clinical Relevance: The TSH-stimulation test with rhTSH is a valuable diagnostic tool to assess thyroid function in selected dogs in which a diagnosis of hypothyroidism cannot be based on basal T(4) and cTSH concentrations alone.

Objective: To evaluate whether use of recombinant human (rh) thyroid-stimulating hormone (TSH) induces equivalent stimulation, compared with bovine TSH (bTSH), and to evaluate activity of rhTSH in dogs of various large breeds., Animals: 18 healthy research Beagles and 20 healthy client-owned dogs of various breeds with body weight > 20 kg., Procedures: The 18 Beagles were randomly assigned to 3 groups, and each dog received either 75 microg of rhTSH, IM or IV, or 1 unit of bTSH, IM, respectively, in a crossover design. The 20 client-owned dogs received 75 microg of rhTSH, IV. Blood samples were taken before and 6 hours after TSH administration for determination of total serum thyroxine (T(4)) concentration. Additional blood samples were taken after 2 and 4 hours in Beagles that received rhTSH, IM., Results: There was a significant increase in T(4) concentration in all dogs, but there were no differences between values obtained after administration of bTSH versus rhTSH or IV versus IM administration of rhTSH. Although there was a significant difference in age and body weight between Beagles and non-Beagles, there was no difference in post-TSH simulation T(4) concentration between the 2 groups., Conclusions and Clinical Relevance: Results indicated an equivalent biological activity of rhTSH, compared with bTSH. Use of 75 microg of rhTSH, IV, did not induce a different magnitude of stimulation in large-breed dogs, compared with Beagles. Euthyroidism was confirmed if post-TSH simulation T(4) concentration was > or = 2.5 microg/dL and at least 1.5 times basal T(4) concentration.

Objective: To evaluate the effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism (PDH), compare the degree of reduction of aldosterone with that of cortisol, and compare aldosterone concentrations of healthy dogs with those of dogs with PDH., Animals: 17 dogs with PDH and 12 healthy dogs., Procedure: For dogs with PDH, the initial dose of trilostane was selected in accordance with body weight. A CBC count, serum biochemical analyses, and ACTH stimulation tests were performed in each dog. Dogs were evaluated 1, 3 to 4, 6 to 8, and 10 to 12 weeks after initiation of treatment. Healthy dogs were evaluated only once., Results: Serum aldosterone concentrations before ACTH stimulation did not change significantly after initiation of treatment with trilostane. At each evaluation after initiation of treatment, serum aldosterone concentrations after ACTH stimulation were significantly lower than corresponding concentrations before initiation of treatment. The overall effect of trilostane on serum aldosterone concentration was less pronounced than the effect on serum cortisol concentration. Median potassium concentrations increased slightly after initiation of treatment with trilostane. Dogs with PDH had significantly higher serum aldo sterone concentrations before and after ACTH stimulation than healthy dogs., Conclusions and Clinical Relevance: Treatment with trilostane resulted in a reduction in serum cortisol and aldosterone concentrations in dogs with PDH, although the decrease for serum aldosterone concentration was smaller than that for serum cortisol concentration. There was no correlation between serum concentrations of aldosterone and potassium during treatment.

Objective: To evaluate an electrolyte analyzer for measurement of ionized calcium (Ca(i)) and magnesium (Mg(i)) concentrations in blood, plasma, and serum; investigate the effect of various factors on measured values; and establish reference ranges for Ca(i) and Mg(i) in dogs., Animals: 30 healthy adult dogs of various breeds., Procedure: Precision in a measurement series, day-to-day precision, and linearity were used to evaluate the analyzer. The effects of exposure of serum samples to air, type of specimen (blood, plasma, or serum), and storage temperature on sample stability were assessed. Reference ranges were established with anaerobically handled serum., Results: The coefficient of variation for precision in a measurement series was < or = 1.5% for both electrolytes at various concentrations. The Ca(i) and Mg(i) concentrations were significantly lower in aerobically handled serum samples, compared with anaerobically handled samples. The Ca(i) and Mg(i) concentrations differed significantly among blood, plasma, and serum samples. In anaerobically handled serum, Ca(i) was stable for 24 hours at 22 degrees C, 48 hours at 4 degrees C, and 11 weeks at -20 degrees C; Mg(i) was stable for 8 hours at 22 degrees C, < 24 hours at 4 degrees C, and < 1 week at -20 degrees C. In anaerobically handled serum, reference ranges were 1.20 to 1.35 mmol/L for Ca(i) and 0.42 to 0.58 mmol/L for Mg(i)., Conclusions and Clinical Relevance: The electrolyte analyzer was suitable for determination of Ca(i) and Mg(i) concentrations in dogs. Accurate results were obtained in anaerobically handled serum samples analyzed within 8 hours and kept at 22 degrees C.

Objective: To compare serum concentrations of 1,25-dihydroxycholecalciferol (1,25-[OH]2D3) and 25-hydroxycholecalciferol (25-[OH]D3) in healthy control dogs and dogs with naturally occurring acute renal failure (ARF) and chronic renal failure (CRF)., Animals: 24 control dogs, 10 dogs with ARF, and 40 dogs with CRF., Procedure: Serum concentrations of 1,25-(OH)2D3 were measured by use of a quantitative radioimmunoassay, and serum concentrations of 25-(OH)D3 were measured by use of a protein-binding assay., Results: Mean +/- SD serum concentration of 1,25-(OH)2D3 was 153 +/- 50 pmol/L in control dogs, 75 +/- 25 pmol/L in dogs with ARF, and 93 +/- 67 pmol/L in dogs with CRF. The concentration of 1,25-(OH)2D3 did not differ significantly between dogs with ARF and those with CRF and was in the reference range in most dogs; however, the concentration was significantly lower in dogs with ARF or CRF, compared with the concentration in control dogs. Mean +/- SD concentration of 25-(OH)D3 was 267 +/- 97 nmol/L in control dogs, 130 +/- 82 nmol/L in dogs with ARF, and 84 +/- 60 nmol/L in dogs with CRF. The concentration of 25-(OH)D3 was significantly lower in dogs with ARF or CRF, compared with the concentration in control dogs., Conclusions and Clinical Relevance: The concentration of 1,25-(OH)2D3 was within the reference range in most dogs with renal failure. Increased serum concentrations of parathyroid hormone indicated a relative deficiency of 1,25-(OH)2D3. A decrease in the serum concentration of 25-(OH)D3 in dogs with CRF appeared to be attributable to reduced intake and increased urinary loss.

Objective: To determine the efficacy of trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor, in dogs with pituitary-dependent hyperadrenocorticism (PDH)., Animals: 11 dogs with PDH., Procedure: The initial dose of trilostane was 30 mg, PO, q 24 h for dogs that weighed < 5 kg and 60 mg, PO, q 24 h for dogs that weighed > or = 5 kg. A CBC count, serum biochemical analyses, urinalysis, ACTH stimulation test, and ultrasonographic evaluation of the adrenal glands were performed in each dog 1, 3 to 4, 6 to 7, 12 to 16, and 24 to 28 weeks after initiation of treatment., Results: All dogs responded well to treatment. All had reductions in polyuria-polydipsia and panting and an increase in activity. Polyphagia decreased in 9 of 10 dogs, and 9 of 11 dogs had improvement of coat quality and skin condition. Concentration of cortisol after ACTH stimulation significantly decreased by 1 week after initiation of treatment. After treatment for 6 months, clinical signs resolved in 9 dogs. In the other 2 dogs, marked clinical improvement was reported for 1 dog, and moderate improvement was reported in the other dog. Ultrasonographically, there was a considerable change in the parenchyma and an increase in size of the adrenal glands. Adverse effects consisted of 1 dog with transient lethargy and 1 dog with anorexia., Conclusions and Clinical Relevance: Trilostane is an efficacious and safe medication for treatment of dogs with PDH. Additional studies in a larger group of dogs and characterization of progressive changes in adrenal glands are needed.