Comparison of the effects of open-tube and evacuated tube-assisted sampling methods on thromboelastography variables for blood samples from healthy dogs.

OBJECTIVE: To compare the effects of open-tube blood sampling with previously investigated blood sampling methods via evacuated tube on thromboelastography variables for blood samples from dogs. ANIMALS: 10 healthy Beagles from the research colony owned by the Clinic of Small Animal Internal Medicine, University Veterinary of Medicine, Vienna, were used. PROCEDURES: In this prospective study, blood was sampled from each dog serially into citrate solution-containing tubes via 20-gauge needle. One evacuated tube was filled from a jugular vein via the evacuated tube port, and the second tube was opened and filled by catching blood flowing through the needle from a lateral saphenous vein. Venipuncture quality was scored with a previously described method. Thromboelastography was performed for each sample. RESULTS: Inferential statistics used with the Wilcoxon signed rank test showed significant differences in reaction time (R) of 3.43 ± 0.84 minutes versus 4.53 ± 0.62 minutes (mean ± SD) between evacuated tube assisted and open-tube sampling, respectively. No other significant differences were identified. CLINICAL RELEVANCE: The sampling methods compared have a small but significant effect on R in thromboelastographic analysis for blood samples from healthy dogs. Shear stress by vacuum sampling seems to accelerate coagulation in jugular blood samples harvested by evacuated tube, resulting in a shortened R. Results suggested that the open-tube method avoids shear stress induced activation of coagulation and is an appropriate sampling method for thromboelastography when used within a standardized protocol.

Aldosterone Is Positively Associated With Circulating FGF23 Levels in Chronic Kidney Disease Across Four Species, and May Drive FGF23 Secretion Directly.

BACKGROUND: Chronic kidney disease (CKD) is accompanied by increases in circulating fibroblast growth factor 23 (FGF23) and aldosterone levels. Here, we tested the hypothesis that aldosterone may be one of the driving forces behind increased FGF23 secretion in CKD. METHODS: Using data from a prospective study in humans, a retrospective study in dogs and cats, and an experimental study in 5/6-nephrectomized mice, we analyzed the relationship between circulating FGF23 and serum aldosterone levels in CKD across four species. To assess the effects of acute inhibition of aldosterone signaling on circulating FGF23, we acutely treated mice with established CKD with the mineralocorticoid receptor blocker canrenone (50 mg/kg iv/sc), and measured intact FGF23 before and 24 h as well as 72 h after start of administration of the drug. RESULTS: We found a tight positive association between circulating intact FGF23 and serum aldosterone in human, canine, and feline CKD patients, as well as in experimental murine CKD (humans: r S = 0.57, p = 0.0368; dogs: r S = 0.66, p = 0.0019; cats: r S = 0.75, p = 0.0003; mice: r S = 0.49, p = 0.0004). Injection of canrenone in mice with established CKD did not lead to changes in FGF23 levels within 24 h, but reduced FGF23 in all mice at 72 h. CONCLUSION: Aldosterone may drive enhanced FGF23 secretion in CKD, possibly explaining the tight positive association between circulating intact FGF23 and aldosterone in human, canine, and feline CKD patients as well as in experimental CKD models.

Comparison of pulmonary deposition of nebulized 99m technetium-diethylenetriamine-pentaacetic acid through 3 inhalation devices in healthy dogs.

BACKGROUND: Inhalation treatment frequently is used in dogs and cats with chronic respiratory disease. Little is known however about the performance of delivery devices and the distribution of aerosolized drugs in the lower airways. OBJECTIVE: To assess the performance of 3 delivery devices and the impact of variable durations of inhalation on the pulmonary and extrapulmonary deposition of nebulized 99m technetium-diethylenetriamine-pentaacetic acid (99m Tc-DTPA). ANIMALS: Ten university-owned healthy Beagle dogs. METHODS: Prospective crossover study. Dogs inhaled the radiopharmaceutical for 5 minutes either through the Aerodawg spacer with a custom-made nose-muzzle mask, the Aerochamber spacer with the same mask, or the Aerodawg spacer with its original nose mask. In addition, dogs inhaled for 1 and 3 minutes through the second device. Images were obtained by 2-dimensional planar scintigraphy. Radiopharmaceutical uptake was calculated as an absolute value and as a fraction of the registered dose in the whole body. RESULTS: Mean (±SD) lung deposition for the 3 devices was 9.2% (±5.0), 11.4% (±4.9), and 9.3% (±4.6), respectively. Differences were not statistically significant. Uptake in pulmonary and extrapulmonary tissues was significantly lower after 1-minute nebulization, but the mean pulmonary/extrapulmonary deposition ratio (0.38 ± 0.27) was significantly higher than after 5-minute nebulization (0.16 ± 0.1; P = .03). No significant differences were detected after 3- and 5-minute nebulization. CONCLUSION AND CLINICAL IMPORTANCE: The performance of a pediatric spacer with a custom-made mask is comparable to that of a veterinary device. One-minute nebulization provides lower pulmonary uptake but achieves a better pulmonary/extrapulmonary deposition ratio than does 5-minute nebulization.

Itraconazole-loaded nanostructured lipid carriers (NLC) for pulmonary treatment of aspergillosis in falcons.

Aspergillosis is the most common and most lethal disease in captive falcons, which is most effectively treated with the poorly soluble drug Itraconazole. To obtain a high drug concentration at the side of infection, the falcon's respiratory system, an isotonic, sterile, non-toxic NLC formulation loaded with Itraconazole was developed for pulmonary application. Itraconazole-loaded NLC had a particle size well in the nanometer range and possessed a narrow particle size distribution. An entrapment efficiency of 99.98% was achieved. A good storage stability of the formulation over 6months was found. Neither by MTS nor by LDH assay cytotoxic effects were determined on the cell line A549, indicating a good tolerability after inhalation. No physical instabilities of Itraconazole-loaded NLC could be detected nebulizing the formulation with a new nanonebulizer into a therapeutic chamber for the treatment of falcons. It could be shown, that the particle size of the aerosol generated nebulizing Itraconazole-loaded NLC with the nanonebulizer was in the nanometer range, providing the possibility to penetrate into the respiratory tract of falcons. By scintigraphy deposition of Itraconazole-loaded NLC in the lung and the air sacs of a patient was shown, being a prerequisite for the pulmonary treatment of aspergillosis in falcons.

Preclinical evaluation of (99m)Tc labeled chondroitin sulfate for monitoring of cartilage degeneration in osteoarthritis.

PURPOSE: In previous in-vitro and ex-vivo studies we proved the specific uptake of (99m)Tc radiolabeled chondroitin sulfate (CS) in human articular cartilage. As a logical next step for the clinical use for imaging osteoarthritis we investigated in-vivo uptake of (99m)TcCS in dogs. PROCEDURES: The radiolabeling of CS Condrosulf (IBSA, Lugano, Switzerland) was performed using 25mg of CS and 20-40MBq/kg body weight of (99m)Tc by means of the tin method. In-vivo uptake of (99m)TcCS was evaluated in dogs (n=12, castrated males, 4-9years, with 15-51kg body weight). 6 healthy dogs served as controls and 6 with clinical and radiological signs of osteoarthritis in the carpal, elbow, and tarsal joint were examined. The tracer was i.v. injected into the external cephalic vein. The uptake was monitored after 2, 4, 6 and 24h in healthy and osteoarthritic dogs using a planar gamma camera by regional planar or whole body ventral and dorsal acquisition. For whole body scintigraphy animals were under general anesthesia, for planar under sedation only. RESULTS: In healthy control dogs we did not detect any specific uptake of (99m)TcCS in the cartilage. In contrast, in the diseased dogs suffering from osteoarthritis a significant, specific, persistent uptake between 4 and 6h in tarsal, carpal and cubital joints was documented. Median target (joint) to background (mid antebrachium) ratio (T/B) in the OA joints after 4, 6, and 24h was significantly higher than in healthy controls. Target to background ratio using soft tissue as a background (T/S) a similar significantly higher than in healthy controls. In all osteoarthritic joints we found a significant positive correlation (r=0.8, n=20) between grade of disease (I-III) and T/B. When matching radiographic (X ray) changes in osteoarthritic joints (grade II and III) we found also a maximal uptake of (99m)TcCS at the specific anatomical site of highest cartilage degeneration. None of the dogs experienced any side effects. CONCLUSION: These results suggest that (99m)TcCS might become a promising diagnostic tool for imaging osteoarthritis. More extensive and detailed examinations are required, however, before extending this methodology for application in humans.

Hypochloremia in cats - prevalence and associated diseases.

OBJECTIVE: To describe the prevalence and possible causes of hypochloremia in the local hospital cat population. MATERIAL AND METHODS: Retrospective study consisting of two parts. Data were collected from the local electronic medical records database using the search terms "chloride" and "cats" (part A), and "blood gas analysis" and "cats" (part B). The medical records of the hypochloremic cats were then reviewed to determine prior treatment or infusions and to identify major underlying disease processes. Part A included an age and gender matched non-hypochloremic control group, whereas in part B acid-base status was assessed. RESULTS: Hypochloremia was detected in 367 (27%) of 1363 blood samples. The application of a correction formula to adjust for free water changes decreased the number of hypochloremic cats to 253 (19%). Only a minority had received glucocorticoids or loop diuretics and the prevalence of vomiting was 44%. Common associated disorders were gastrointestinal and respiratory diseases, as well as azotemia and diabetes mellitus. Polyuria/polydipsia, dehydration, prednisolone or furosemide pretreatment, azotemia and diabetes mellitus increased, whereas fluid therapy and the diagnosis of neoplasia decreased the prevalence of hypochloremia. An inverse correlation was found between corrected chloride and standardized base excess (rs = -0.597, p = 0.001) as well as anion gap (rs = -0.4, p = 0.026). 99% of the hypochloremic cats had derangements of acid-base balance. CONCLUSION: Hypochloremia is a common electrolyte disorder in the local cat population. The correction formula is necessary to adjust for changes in plasma osmolality. Although associated with metabolic alkalosis, most of the hypochloremic cats have a normal or decreased pH. The inverse correlation of chloride and anion gap als well as the high proportion of azotemic or diabetic animals support the concept of compensatory acidosis induced hypochloremia. CLINICAL RELEVANCE: Hypochloremia should prompt the clinician to performe blood-gas analysis. Diabetes mellitus (especially ketoacidosis) and renal disease should be included in current algorithms for the evaluation of hypochloremic patients.

Concomitant liposomal doxorubicin and daily palliative radiotherapy in advanced feline soft tissue sarcomas.

Local recurrence of feline soft tissue sarcomas is common despite aggressive treatment. Liposomal doxorubicin might serve as a depot radiosensitizer if administered concomitantly with daily radiotherapy and thus improve tumor control. In this pilot study, the feasibility of concomitant liposomal radiochemotherapy was evaluated in a palliative setting in 10 cats with advanced soft tissue sarcomas. Cats were treated with median number of 5 (range 5-7) daily fractions of radiotherapy and a median total dose of 20 Gy (range 20-31.5 Gy). One dose of liposomal doxorubicin was administered at the beginning of radiotherapy. Seven cats received further free or liposomal doxorubicin after completion of the liposomal doxorubicin/radiation protocol. Seven of the treated 10 cats (70%) achieved a partial (n=5) or complete (n=2) response with a median response duration of 237 days. The median progression free interval in all 10 cats was 117 days and the median overall survival time was 324 days. Concomitant liposomal radiochemotherapy was tolerated well in nine cats, one cat experienced temporary anorexia. Although the number of patients is too small to make definitive conclusions, results appear promising enough to investigate the role of liposomal doxorubicin as a radiosensitizer further.

Chemotherapy in canine acute megakaryoblastic leukemia: a case report and review of the literature.

Acute myeloid leukemia (AML) in dogs is a rare disease with poor prognosis. In most subjects, palliative treatment or euthanasia is performed. A 3.5-year-old male castrated labrador with AML-M7, which was treated with induction polychemotherapy (8 cycles) using vincristine (0.5 mg/m(2)/cycle), daunorubicin (20 mg/m(2)/cycle), cytosine arabinoside (ARA-C, 100 mg/m(2)/cycle) and prednisolone (1 mg/kg/day) is reported. Treatment was well tolerated and complete remission was achieved. Postinduction chemotherapy consisted of ARA-C, daunorubicin and prednisolone. After 3, 5 and 18 months, the subject relapsed. Each relapse was treated with ARA-C (up to 1,000 mg/m(2)) and etoposide or daunorubicin. Again, no severe side-effects occurred and the disease was controlled, with 37 chemotherapy-cycles (ARA-C, 3 x 1,000 mg/m(2)/cycle), for 24 months. Based on a literature-search, this is the first report documenting a long-term response of canine AML, probably resulting from the high-dose ARA-C. Clinical trials using high-dose ARA-C are now required to confirm antileukemic efficacy in canine leukemias.

Evaluation of biological variance of cystatin C in comparison with other endogenous markers of glomerular filtration rate in healthy dogs.

BACKGROUND: The aim of the study was to investigate and compare components of variance of endogenous markers of glomerular filtration rate (GFR) in healthy dogs and impact on the interpretation of results. HYPOTHESIS: Cystatin C (cysC) in the dog is superior to creatinine (crea) and urea in detecting decreased renal function because of a high index of individuality (IoI). ANIMALS AND METHOD: Variance components of cysC, crea (2 methods: creaE, creaJ), urea, and inorganic phosphate (Pi) in plasma were determined in a longitudinal study over 6 months in 24 healthy dogs (6 German Shorthair Pointers, 18 Beagles). IoI and critical differences (CD) were calculated, as well as the numbers of measurements necessary to determine the individual's homeostatic set point. RESULTS: Mean concentrations of cysC, creaJ, creaE, urea, and Pi (mean +/- SD) were 0.93 +/- 0.19 mg/L, 0.94 +/- 0.17 mg/dL, 0.76 +/- 0.18 mg/dL, 35.34 +/- 9.08 mg/dL, and 3.74 +/- 0.68 mg/dL, respectively. The IoI for cysC, creaJ, creaE, urea, and Pi were 0.96, 0.89, 0.80, 0.90, and 1.16, respectively. The C(D) for cysC, creaJ, creaE, urea, and Pi were 0.37 mg/L, 0.26 mg/dL, 0.27 mg/dL, 16.94 mg/dL, and 1.45 mg/dL, respectively. CONCLUSION: In dogs, components of biological variance of cysC and crea are in the same range. Analytical precision requirements were fulfilled by crea(both), urea, and Pi. All parameters had an intermediate IoI, which allowed the application of population-based reference limits. The application of the CD for crea or cysC might be useful in detecting a decrease of GFR, when sequential measurements in an individual reveal an increase exceeding the CD but not the upper reference limit.