Comparison of the pharmacokinetic profiles of two different amphotericin B formulations in healthy dogs

This study was conducted to compare the pharmacokinetic profiles of conventional (Fungizone^®) and liposomal amphotericin B (AmBisome^®) formulations in order to predict their therapeutic properties, and evaluate their potential differences in veterinary treatment. For this purpose, twelve healthy mixed breed dogs received both drugs at a dose of 0.6 mg/kg by intravenous infusion over a 4‐min period in a total volume of 40 ml. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72 and 96 hr after dosing, and concentrations of drug in plasma were determined by high‐performance liquid chromatography (HPLC). Pharmacokinetics was described by a two‐compartment model. Although both formulations were administered at the same doses (0.6 mg/kg), the plasma pharmacokinetics of liposomal amphotericin B differed significantly from those of amphotericin B deoxycholate in healthy dogs (p < .05). Liposomal amphotericin B showed markedly higher peak plasma concentrations (approximately ninefold greater) and higher area under the plasma concentration curve values (approximately 14‐fold higher) compared to conventional formulation. It is concluded that AmBisome^® reached higher plasma concentration and lower distribution volume and had a longer half‐life compared to Fungizone^®, and therefore, AmBisome^® is reported to be an appropriate and effective choice for the treatment of systemic mycotic infections in dogs.     

Serum bile acids: reference values in healthy dogs and comparison of two kit methods

Serum bile acid (SBA) reference intervals were established by use of a radioimmunoassay method for fasting dogs to be 0.2 to 4.3 micro mol/L (n = 60) and for 2 hour postprandial samples to be 0.6 to 24.2 micro mol/L (n = 37). The SBA reference intervals estimated using an enzymatic method were 0 to 8.6 micro mol/L for fasting (n = 26) and 0 to 29.8 micro mol/L for 2 hour postprandial samples (n = 36). The correlation between the two methods including samples from healthy dogs and clinical cases is good (n = 128, r = 0.82, p < 0.0001). The radioimmunoassay method is linear to 50 micro mol/L and the enzymatic method is linear to 100 micro mol/L, thus both methods require serum dilutions to be made in many cases of primary liver disease. The enzymatic method is less expensive and more convenient for use in a clinical laboratory but requires a greater sample volume (400 micro I) than the RIA method (50 micro I). Both methods have adequate precision and accuracy to be useful as diagnostic tests of liver function in dogs.     

A comparison of two different methods for dead space measurements in ventilated dogs

The aim of the study was to compare two methods of measuring physiological dead space/tidal volume ratio (Vd /Vt ) and alveolar dead space (Vd _ALV). Measurements were obtained by automated single breath CO₂ analysis (Ventrak 1550/Capnoguard 1265 (V&C)) and classical calculations were carried out using the Enghoff–Bohr equation in anaesthetized dogs. The V&C consists of a mainstream capnometer, a pneumotachometer, a signal processor, and computer software to determine continuous single‐breath CO₂ analysis (SBT‐CO₂). Eleven dogs of mixed breed (five female, six male) mean body mass 35 ± 10 kg, aged 9 months to 8 years were studied. Pre‐anaesthetic medication was acepromazine (0.03 mg kg^?1) and methadone (0.1 mg kg^?1). Anaesthesia was induced with propofol given to effect and maintained with propofol (10 mg kg^?1 hour^?1) and fentanyl (0.02 mg kg^?1 hour^?1) by infusion. The dog's trachea were intubated and the carbon dioxide and flow sensor were placed between the tube and the Y‐piece of a circle system (Fi O₂ = 1.0). Controlled ventilation was started (tidal volume 10–15 mL kg^?1) and settings were not changed throughout the measurement period. Mixed expired PCO₂ (P e ?CO₂) was measured by analyzing expired gas collected in a mixing box in the expiratory limb of the circle system. The dorsal pedal artery was cannulated for arterial blood sampling and analysis. Measurements were done every 15 minutes for 1 hour. The Vd /Vt was automatically calculated and displayed from the SBT‐CO₂ analysis and also obtained using the Enghoff modification of the Bohr equation (Vd /Vt = (PaCO₂ ? P e ?CO₂)/PaCO₂). Alveolar dead space was determined by calculating the physiological dead space (Vd phys = expired volume × (Vd /Vt )) and subtracting the anatomical dead space measured by SBT‐CO₂. Values for Vd /Vt and Vd _ALV obtained with both methods were compared using Students t‐test. The mean values from the automatic dead space calculation (Vd /Vt : 0.62–0.63; Vd _ALV: 56.1–64.3 mL) did not differ significantly from those calculated arithmetically (Vd /Vt : 0.62–0.63; Vd _ALV: 54.09–66.31 mL). The mean differences and standard deviation in Vd /Vt was 0.63 ± 0.00 and in Vd _ALV 58.98 ± 4.28 mL for the two measurement techniques. Our data indicate that V&C can be used for accurate noninvasive online Vd /Vt and Vd _ALV measurements in anaesthetized ventilated dogs.     

Nephrotoxicity of sodium arsenate in dogs

Nephrotoxicity of sodium arsenate was evaluated in dogs to determine the pathophysiologic basis for renal lesions caused by this heavy metal. Examination of biopsy specimens indicated that the low dose of the As salt (0.73 mg/kg of body weight) produced histologic changes consisting of mild degeneration and vacuolation of renal tubular epithelium. Vacuolation involved mainly the ascending thick portion of the nephron. Clinical pathologic changes were not demonstrable at this dosage level according to glomerular filtration rate (creatinine clearance), fractional reabsorption of sodium, potassium, and chloride; plasma osmolar and free water clearance; and urinalysis. The medium dose (7.33 mg/kg) resulted in alterations determined by urinalysis, but did not markedly affect other clinical pathologic measurements. Histopathologic changes were equal to or greater than those seen with the low dose. Tubular necrosis was observed in the cortical portion of the nephron and the ascending thick limb. The high dose (14.66 mg/kg) consistently produced marked changes in all parameters evaluated. Clinical pathologic alterations were compatible with acute tubular necrosis involving all segments of the nephron. Histologically, moderate glomerular sclerosis and severe tubular necrosis were observed. During recovery from the high dose of As, a gradual compensatory healing process was observed that was evident in all clinical pathologic parameters and was confirmed from sequential renal biopsy specimens.     

Plasma salicylate concentrations in immature dogs following aspirin administration: comparison with adult dogs

Aspirin disposition in immature and adult dogs, assessed by plasma salicylate concentrations following single doses of aspirin given orally (p.o.) and intravenously (i.v.), was compared. Using a cross-over design, four immature (12–16-weeks-old) and eight adult (1– 2-years-old) dogs were given a single dose of aspirin at 17.5 mg/kg body weight i.v. and a single dose of buffered aspirin at 35 mg/kg body weight p.o. Blood was collected from the jugular vein for 24 h following each dose. A fluorescence polarization immunoassay was used for determination of salicylate in plasma. Significant differences in aspirin disposition were identified between the two groups. Immature dogs had significantly shorter salicylate half-life, lower mean residence time, and more rapid salicylate clearance than adult dogs. The difference in volume of distribution between the two groups was not significantly different. Immature dogs had lower mean (± SD) peak plasma salicylate concentrations (64.5 ± 2.38 mg/L) than adult dogs (95.9 ± 12.2 mg/L) following a single oral dose of buffered aspirin at 35 mg/kg body weight. Predicted plasma salicylate concentration-time curves were constructed for various aspirin dosage regimens. This analysis showed that the previously recommended buffered aspirin dose for adult dogs of 25 mg/kg body weight p.o. every 8 h would be ineffective in maintaining plasma salicylate concentrations > 50 mg/L in immature dogs.     

Evaluation of two methods of endotracheal tube selection in dogs

This study evaluated two methods of endotracheal tube selection using 28 fresh canine carcasses of various ages, weights, and genders. The two selection methods were 1) nasal septal width pairing with outer diameter of an endotracheal tube, and 2) digital palpation of the tracheal outer diameter to determine the endotracheal tube size. All dogs were dolichocephalic breeds. Results of this study showed that the canine nasal septal width method of endotracheal tube selection was correlated with the size of the tracheal internal (r=0.72) and outer (r=0.73) diameters. However, evidence shows that the digital palpation method is slightly more effective than the nasal width method in selecting the best-fitting endotracheal tube. The percentage of the best-fit tube selection for the nasal septal width method was 21%, while the digital palpation method was 46%. With these two methods, selecting an endotracheal tube that is too small is possible, especially when the tube internal diameter is > or =7 mm.     

Tetramine cupruretic agents: a comparison in dogs

The cupruretic effects of 2 tetramine (N,N'-bis (2-aminoethyl) alkane diamine) chelators were examined in healthy dogs fed a commercial dog food containing 12.2 micrograms of copper/g of dry diet. Two groups of 3 dogs each were given either 300 mg of 2,2,2-tetramine tetrahydrochloride or 2,3,2-tetramine tetrahydrochloride for 23 consecutive days. Serum and 24-hour urine samples obtained before drug administration and during therapy were analyzed for copper, zinc, and iron concentrations. Both tetramines produced a significant cupruresis without significant changes in serum copper or in serum or urine zinc and iron concentrations. The 2,3,2-tetramine tetrahydrochloride produced a 4- to 9-fold greater cupruresis than did 2,2,2-tetramine tetrahydrochloride and resulted in a daily loss of more than 2 mg of copper in the urine. The dogs had no laboratory or clinical evidence of toxic side effects to either cupruretic agent during the treatment period. The results of the present study indicate that 2,3,2-tetramine should be an effective decoppering drug for use in dogs.     

Ichthyosis in two dogs.

Ichthyosis in 2 dogs was characterized by extreme hyperkeratosis on all or part of the skin and by extreme thickening of the digital and metapodial pads. The skin disorder closely resembled human lamellar ichthyosis, in which the histologic features include a thickened granular layer, mitotic figures, and dense collections of coarse keratohyaline granules. The disease was believed to be inherited, probably autosomal recessive, inasmuch as none of the parents was affected. Treatment of 1 dog with 5% lactic acid in hydrophilic ointment reduced the hyperkeratosis and decreased the shedding of scales.     

Evaluation of the arterial blood pressure of dogs by two noninvasive methods.

The determination of the arterial blood pressure was done on 12 healthy mixed breed dogs in both the anesthetized and the conscious state, to evaluate two instruments (Doppler flow detector and infrasonde D4000), in their ability to indirectly determine arterial blood pressure. The coefficients of variation were higher with indirect methods when compared with the results obtained by cannulation. These coefficients were lower with the Doppler flow detector. The correlation study showed that both apparatuses were reliable in most situations. The infrasonde D4000 was more accurate than the Doppler in the conscious animals. However the results showed a lack of precision in hypertensive conscious dogs. The diastolic arterial blood pressure was particularly precise in the case of the anesthetized hypotensive dogs. Its sensitivity allowed it to register muscle movement artifacts. The Doppler flow detector showed less variation and was particularly accurate in both anesthetized and conscious hypertensive dogs. Its sensitivity allowed artifact movement sounds to be detected. The Doppler should be used in quiet surroundings or earphones should be worn by the evaluator. Some form of restraint is needed with the use of both instruments. Even if the correlations with the direct arterial blood pressure values were better with the infrasonde D4000, greater variations were found in the individual readings. The Doppler instrument represents in the hands of the investigators a better instrument for routine monitoring of blood pressure in the dog.     

Comparison of two formaldehyde administration methods of in ovo-injected eggs

Formaldehyde administration in the hatchery can be very useful in decreasing microbial numbers. However, its use is controversial because of the adverse effects that can occur to chicks and people. This study was designed to look at alternative methods of application of formaldehyde in the hatchery. In addition, the study compared the effects of these methods of application on in ovo-and non-in ovo-injected eggs. All in ovo-injected eggs were given diluent only with no vaccine or antibiotic added. In hatchers containing both in ovo-injected eggs and non-in ovo-injected eggs, formaldehyde was administered two ways, dose (DOSE) and constant rate infusion (CRI). In the DOSE hatcher, 12 ml of formaldehyde was administered at one time every 12 hr, whereas in the CRI hatcher, the same volume was administered at a rate of 1 ml/hr over a 12-hr period. A control (CONT) hatcher received 12 ml of distilled water at the same time that the DOSE hatcher was given formaldehyde. In the DOSE hatcher, a peak concentration of formaldehyde of 102 ppm was reached. The CRI was maintained at approximately 20 ppm of formaldehyde. At pipping, the aerosol bacterial load in the hatchers receiving formaldehyde (DOSE, 130 colony-forming units [CFU]/m3; CRI, 82.5 CFU/m3) was significantly less than in the CONT hatcher (235 CFU/m3). At hatch, the CRI (337.5 CFU/m3) was not able to control bacterial levels and only the DOSE hatcher (150 CFU/m3) had a significantly lower aerosol bacterial count. The CRI non-in ovo-injected eggs (93.39%) had a significantly higher percentage of hatch of fertile compared with non-in ovo-injected eggs exposed to water (84.27%). In ovo-injected eggs in CONT and DOSE treatment groups contained significantly higher percentages of visual contamination than non-in on-injected eggs in the same hatchers. This difference had numerical significance only in the treatment groups within the CRI hatcher. The chicks were then placed into replicate treatment groups and grown for 14 days. Chicks from the CRI in ovo-injected eggs had a statistically significant improvement in feed conversion ratio (1.24) at 14 days when compared with chicks from CONT non-in ovo-injected eggs (1.29). All formaldehyde-exposed chicks had numerically lower feed conversion ratios compared with the CONT exposed chicks.     

Aplastic anemia associated with prolonged high-dose trimethoprim-sulfadiazine administration in two dogs

Trimethoprim-sulfadiazine (TMP-SDZ) (Tribressin tablets 120 - 100 mg sulfadiazine, 20-mg trimethoprim [Coopers Animal Health, Inc., A Pitman-Moore Company, Mundelein, Ill.]) is a broad spectrum antibiotic combination effective in the treatment of bacterial pneumonia, urinary tract infections, pyoderma, meningitis, and prostatitis.(1) In clinical trials in puppies and adult dogs, TMP-SDZ was considered safe at both the manufacturer's recommended dose (15 mg/kg, b.i.d., or 30 mg/kg, u.i.d., per os for < 14 days(2)) and at 10 times that dose for 20 dayS.(3) Many infections, however, require prolonged high-dose therapy for resolution. The following study describes two cases of aplastic anemia and sepsis associated with intermittent, chronic (17-25 days), high-dose (25-30 mg/kg, b.i.d., per os) TMP-SDZ therapy recommended for the treatment of pyoderma.(4-7)     

Diagnosis of gastrointestinal parasites in reptiles: comparison of two coprological methods

Background

Exotic reptiles have become increasingly common domestic pets worldwide and are well known to be carriers of different parasites including some with zoonotic potential. The need of accurate diagnosis of gastrointestinal endoparasite infections in domestic reptiles is therefore essential, not only for the well-being of captive reptiles but also for the owners. Here, two different approaches for the detection of parasite stages in reptile faeces were compared: a combination of native and iodine stained direct smears together with a flotation technique (CNF) versus the standard SAF-method.

Results

A total of 59 different reptile faeces (20 lizards, 22 snakes, 17 tortoises) were coprologically analyzed by the two methods for the presence of endoparasites. Analyzed reptile faecal samples contained a broad spectrum of parasites (total occurence 93.2%, n = 55) including different species of nematodes (55.9%, n = 33), trematodes (15.3%, n = 9), pentastomids (3.4%, n = 2) and protozoans (47.5%, n = 28). Associations between the performances of both methods to detect selected single parasite stages or groups of such were evaluated by Fisher''s exact test and marginal homogeneity was tested by the McNemar test. In 88.1% of all examined samples (n = 52, 95% confidence interval [CI] = 77.1 - 95.1%) the two diagnostic methods rendered differing results, and the McNemar test for paired observations showed highly significant differences of the detection frequency (P < 0.0001).

Conclusion

The combination of direct smears/flotation proved superior in the detection of flagellates trophozoites, coccidian oocysts and nematode eggs, especially those of oxyurids. SAF-technique was superior in detecting larval stages and trematode eggs, but this advantage failed to be statistically significant (P = 0.13). Therefore, CNF is the recommended method for routine faecal examination of captive reptiles while the SAF-technique is advisable as additional measure particularly for wild caught animals and individuals which are to be introduced into captive collections.     

A comparison of endotracheal and intravenous routes for atropine administration in anaesthetised dogs

The endotracheal route for atropine administration was compared with the intravenous route in 50 anaesthetised dogs. The response to drug administration was recorded as the change in heart rate from a steady pretreatment value. An indication was found of a positive relationship between the dose and the response to atropine given endotracheally. The increase in heart rate following atropine administration was similar, in terms of magnitude and speed of onset, when given by the endotracheal route at 0–06 mg/kg, as compared with that obtained by the intravenous administration of atropine at 0–04 mg/kg (P<0–05).     

Clinical comparison of three methods to measure blood pressure in nonsedated dogs

OBJECTIVE: To determine arterial blood pressure in client-owned dogs, using direct arterial puncture, oscillometry, and Doppler ultrasonography in a clinical setting. DESIGN: Prospective study. ANIMALS: 8 clinically normal client-owned dogs. PROCEDURE: Blood pressures of nonsedated dogs were measured simultaneously, using each of the 3 methods. Mean values obtained were compared with published mean values. Ability of noninvasive methods (Doppler ultrasonography and oscillometry) to accurately predict results of the invasive method, and relationships between blood pressure and age, body weight, and degree of patient anxiety were determined. RESULTS: Calculated ranges of values (mean +/- 2 SD) determined by direct arterial puncture were: systolic pressure, 114 to 194 mm Hg; diastolic pressure, 66 to 102 mm Hg; and mean pressure, 85 to 129 mm Hg. Ranges determined by use of oscillometry were: systolic, 110 to 190 mm Hg; diastolic, 35 to 107 mm Hg; and mean, 78 to 138 mm Hg. Ultrasonographic and oscillometric values did not accurately predict direct values, but mean values of systolic and mean pressures were similar among methods. Relationships were not detected between age or body weight and blood pressure. Significant differences in blood pressure were not detected between anxious and nonanxious dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Mean values of systolic, diastolic, and mean arterial blood pressure measured in nonsedated client-owned dogs, using invasive and noninvasive methods in a clinical setting, are comparable with those determined for acclimatized, trained, or sedated dogs. However, results of noninvasive methods may not accurately reflect direct values.