Evaluation of a point-of-care test for canine C-reactive protein

Background: In veterinary medicine, there is increasing interest in measuring C‐reactive protein (CRP) as a tool for diagnosis and monitoring of inflammatory diseases. Reported CRP concentrations for healthy dogs have ranged from 0 to 8.9 mg/L. Objectives: The aims of this study were to evaluate a canine‐specific point‐of‐care (POC) lateral flow immunoassay for qualitative CRP measurement in healthy and diseased dogs and to compare results with those obtained by a quantitative ELISA. Methods: Blood samples from 73 client‐owned dogs were available for testing: 16 healthy dogs and 57 dogs with a variety of infectious, inflammatory, or neoplastic diseases. CRP was measured in heparinized whole blood samples and serum with the TECOmedical Dog CRP‐visual POC test. A red line develops in the POC device if CRP is ≥5 mg/L, and results are scored as negative or positive. An ELISA validated previously for canine serum was used as the reference method. Results: For all dogs, serum CRP concentrations measured by the ELISA ranged from 0.1 to ≥350 mg/L (median=38 mg/L). Percentages of the CRP POC test results that agreed with the ELISA results were 98.6% for whole blood and 97.3% for serum samples. For serum samples, sensitivity of the POC test was 96.4% and specificity was 81.3%. For whole blood, sensitivity was 94.7% and specificity was 93.8%. Conclusions: The POC test had very good agreement with the ELISA test and had high sensitivity and specificity; therefore, it can be used as a qualitative test to screen for increases in CRP concentrations.     

Urine cortisol:creatinine ratio as a screening test for hyperadrenocorticism in dogs.

A urine cortisol:creatinine (c:c) ratio, determined from a free-catch morning sample, was evaluated in each of 83 dogs as a screening test for hyper-adrenocorticism. The dogs evaluated were allotted to 3 groups, including 20 healthy dogs, 40 dogs with confirmed hyperadrenocorticism (HAC), and 23 dogs with polyuria and polydipsia not attributable to HAC (polyuria/polydipsia group; PU/PD). Overlap in the urine c:c ratios (mean +/- SEM), comparing results from the healthy dogs (5.7 x 10(-6) +/- 0.9) with those from the HAC dogs (337.7 x 10(-6) +/- 72.0) was not found. However, 11 (64%) of the 18 values from the PU/PD dogs (42.6 x 10(-6) +/- 9.4) were above the lowest ratio in the HAC group and 50% of the HAC group had a urine c:c ratio below the highest value in the PU/PD group. When the mean urine c:c ratio (+/- 2 SD) for the group of healthy dogs was used as a reference range, 100% of the HAC dogs and 18 (77%) of 23 dogs in the PU/PD group had abnormal urine c:c ratios. The sensitivity of the urine c:c ratio to discriminate dogs with HAC was 100%. The specificity of the urine c:c ratio was 22% and its diagnostic accuracy was 76%. On the basis of our findings, a urine c:c ratio within the reference range provides strong evidence to rule out HAC. However, abnormal urine c:c ratios are obtained from dogs with clinical diseases other than HAC. Therefore, measurement of a urine c:c ratio should not be used as the sole screening test to confirm a diagnosis of HAC.     

Evaluation of a canine D-dimer point-of-care test kit for use in samples obtained from dogs with disseminated intravascular coagulation, thromboembolic disease, and hemorrhage

OBJECTIVE: To evaluate a canine D-dimer point-of-care (cD-d POC) test kit for use in healthy dogs and dogs with disseminated intravascular coagulation (DIC), thromboembolic disease (TED), and hemorrhage. ANIMALS: 12 healthy dogs, 18 dogs with DIC, 23 dogs with TED (19 acute and 4 chronic), and 18 dogs with hemorrhage. PROCEDURE: The cD-d POC, canine D-dimer ELISA (cD-d ELISA), human D-dimer latex agglutination (hD-d LA), and fibrin degradation product (FDP) tests were performed on citrated plasma. RESULTS: All healthy dogs had negative cD-d POC test results and mean cD-d ELISA value of 0.2 U/mL. All dogs with DIC had positive cD-d POC test results and mean cD-d ELISA value of 44 U/mL. Dogs with acuteTED had a mean cD-d ELISA value of 34 U/mL, and 17 of 19 had positive cD-d POC test results. Mean cD-d ELISA value in dogs with hemorrhage was 14 units/mL, and 15 of 18 had positive cD-d POC test results. The cD-d ELISA values in dogs with hemorrhage were significantly higher than those of healthy dogs but lower than those of dogs with DIC and acute TED. The cD-d POC, cD-d ELISA, and hD-d LA tests were comparable in differentiating healthy dogs from dogs with DIC, acute TED, or hemorrhage and appeared to be superior to measurement of FDPs. CONCLUSIONS AND CLINICAL RELEVANCE: The cD-d POC test kit can be quickly and easily used and reliably detects dogs with DIC or acute TED. Positive results may also be seen in dogs with internal hemorrhage.     

Evaluation of a Portable Meter to Measure Ketonemia and Comparison with Ketonuria for the Diagnosis of Canine Diabetic Ketoacidosis

Background: The diagnosis of canine diabetic ketoacidosis (DKA) usually is based on measurement of urinary acetoacetate (ketonuria). In humans, this test is less sensitive and specific than blood 3-β-hydroxybutyrate (ketonemia) evaluation.
Hypothesis: Ketonemia measurement using a portable meter is more accurate than ketonuria determination with a dipstick to diagnose canine DKA.
Animals: Seventy-two client-owned diabetic dogs with ketonemia, ketonuria, or both.
Methods: Prospective observational study. Based on blood bicarbonate concentration and anion gap, dogs were divided into 2 groups: patients with DKA ( n = 25); patients with diabetic ketosis ( n = 47). Sensitivity, specificity, and positive and negative likelihood ratio (LR) at different cut-off points were determined for both ketonemia and ketonuria. Receiver operating characteristic (ROC) analysis was used to assess the accuracy of each diagnostic test to diagnose DKA.
Results: With regard to ketonemia, cut-off values of 2.3 and 4.3 mmol/L revealed 100% sensitivity and 100% specificity, respectively, whereas cut-off values of 2.8 and 3.5 mmol/L showed a −LR of 0.05 and a + LR of 13.16, respectively. With regard to ketonuria, a cut-off value of 1+ revealed 92% sensitivity, 40% specificity, and −LR of 0.20, whereas a cut-off value of 3+ revealed 44% sensitivity, 94% specificity, and +LR of 6.89. The areas under the ROC curves for the ketonemia and ketonuria tests were significantly different (0.97 and 0.81, respectively, P = .003).
Conclusions and Clinical Importance: Measurement of ketonemia is accurate and more effective than measurement of ketonuria to diagnose canine DKA.     

51Cr-EDTA absorption blood test: an easy method for assessing small intestinal permeability in dogs

The 51Cr-EDTA test is a valuable clinical tool for screening intestinal diseases in dogs. The test is performed by calculating the percentage of recovery from urine of a PO-ingested dose of 51Cr-EDTA after 6 or 24 hours. Careful urine collection is a practical limitation of this test in dogs, and our goal was to develop a simpler test that measures 51Cr-EDTA in blood. A 51Cr-EDTA absorption test was simultaneously performed on urine and serum 43 times in healthy Beagle Dogs. Timed blood samples were withdrawn, and urine was collected during a 6-hour period. Percentages of the ingested dose were then calculated in urine and serum. The mean +/- standard deviation (range) percentage in urine after 6 hours was 14.07 +/- 8.72% (3.81-34.18%), whereas results in serum from samples taken at 2, 3, 4, 5, and 6 hours were 0.49 +/- 0.45% (0.02-2.13%), 0.75 +/- 0.52% (0.03-1.89%), 0.82 +/- 0.57% (0.13-2.21%), 0.70 +/- 0.53% (0.12-1.99%), and 0.47 +/- 0.44% (0.11-1.79%), respectively. The results for blood specimens showed good concordance with those for urine, especially for the samples taken at 4 hours (r = 0.89). Moreover, the correlation between urine and blood was better when the sum of the percentages of the recovered analyte from various blood samples was compared with urine. The correlation coefficient when summing 4 blood samples was excellent (r = 0.97) and remained excellent when summing only 2 blood samples taken at 3 and 5 hours (r = 0.95) or at 3 and 4 hours (r = 0.94). We conclude that a serum 51Cr-EDTA test determined by summing successive blood samples provides an easier means of estimating small intestinal permeability in dogs and gives results comparable to those of the 6-hour urine test.     

Determination of Normal Values Using an Automated Coagulation Timer for Activated Coagulation Time and its Application in Dogs with Hemophilia

The present study was performed to determine normal values for the Medtronic HemoTec automated activated coagulation time (ACT) analyzer (Medtronic HemoTec Inc, Parker, CO, distributed in Switzerland by Convergenza AG, Vaduz, Liechtenstein), and to evaluate its ability to detect dogs with hemophilia. ACT was measured in 43 healthy dogs presented to the Companion Animal Hospital, University of Bern, Bern, Switzerland, with the Medtronic HemoTec ACT analyzer to determine normal values. The mean +/- 2 standard deviations (SDs) of the values obtained was defined as the normal range. ACT was measured 8-10 times on the same day in 6 dogs to determine repeatability. ACT also was measured in 11 dogs with hemophilia and compared with a conventional visual ACT measurement test and with the activated partial thromboplastin time (APTT). ACT values of the 43 dogs used to determine normal values ranged from 66.5 to 97.0 seconds (mean, 79.3 seconds; SD, 7.35 seconds; median, 78.5 seconds). A range of 64-95 seconds (mean +/- 2 SDs) was defined as the normal range for the tested device. Repeatability was poor (r = 0.256). ACT values measured with the automated device did not correlate with ACT values measured with a conventional visual test or with APTT Sensitivity of the test was 90.9%, specificity was 98.0%, and accuracy was 96.7%. Variability in the test results was large and may lead to incorrect results. The automated measurement device was not superior to the conventional visual method in evaluating dogs with hemophilia.     

Evaluation of the i-STAT Alinity v in a veterinary clinical setting

Many point-of-care (POC) analyzers are available for the measurement of electrolytes and acid-base status in animals. We assessed the precision of the i-STAT Alinity v, a recently introduced POC analyzer, and compared it to 2 commonly used and previously validated POC analyzers (i-STAT 1, Stat Profile pHOx Ultra). Precision was evaluated by performing multiple analyses of whole blood samples from healthy dogs, cats, and horses on multiple i-STAT Alinity v analyzers. For comparison between analyzers, whole blood samples from dogs and cats presented to the emergency room were run concurrently on all 3 POC instruments. Reported values were compared by species (dogs and cats only) using Pearson correlation, and all values from all species were analyzed together for the Bland–Altman analysis. Results suggested that the i-STAT Alinity v precision was very good, with median coefficients of variability <2.5% for all measured parameters (except the anion gap), with variable ranges of coefficients of variation. In addition, good-to-excellent correlation was observed between the i-STAT Alinity v and i-STAT 1, and between the i-STAT Alinity v and Stat Profile pHOx Ultra for all parameters in both cats and dogs, respectively. In this cohort, the i-STAT Alinity v had clinically acceptable bias compared to the currently marketed analyzers and can be used for monitoring measured analytes in cats and dogs, although serial measurements in a single animal should be performed on the same analyzer whenever possible.     

Assessment of a point-of-care lactate monitor in emergency admissions of adult horses to a referral hospital

BACKGROUND: Blood lactate concentration [LAC] is considered a useful indicator of disease severity in horses. Agreement of point-of-care (POC) lactate monitors with laboratory standards has not been established for clinically abnormal horses. Hypothesis: It was hypothesized that results from a POC lactate monitor would be in agreement with a laboratory-based measurement of [LAC]. ANIMALS: The study included adult horses presented for emergency evaluation. METHODS: A prospective observational study was performed. [LAC] was measured with whole blood (AWB) and plasma (APL) by means of a POC monitor (Accutrend) and compared with results from whole blood measured by a laboratory blood gas analyzer (NOVA). RESULTS: Samples from 221 horses were used to compare the 2 lactate measurement techniques. Agreement (p +/- SE) was closest between APL and NOVA (0.97 +/- 0.01); an average observed difference of 0.15 +/- 0.89 (mean +/- SD) and 95% limits of agreement (LOA) -1.89, 1.59 also were found. Agreement was preserved and 95% LOA further decreased in horses with NOVA [LAC] of <5 mM and PCV <40%. Agreement was modest when testing whole blood samples on the POC monitor with increased 95% LOA. CONCLUSIONS AND CLINICAL IMPORTANCE: Results indicate close agreement between NOVA and the POC monitor when [LAC] was measured with plasma. Results were less consistent at higher [LAC] but sufficiently reliable to follow trends. Although whole blood may be used with the POC monitor to identify clinically important hyperlactatemia, results may be insufficiently reliable to monitor trends.     

Clearance of nasal mucus in nonanesthetized and anesthetized dogs

Clearance rates for nasal mucus in the maxillary turbinate region were measured in 8 Beagle dogs. 99mTc Macroaggregated albumin (10 microliters) was instilled in the nasal maxillary region of dogs under general anesthesia. A gamma camera was used to detect movement of the 99mTc macroaggregated albumin in the nose for 1 hour after it was instilled. Velocity of mucus was measured in the 8 dogs each under 3 conditions of anesthesia: anesthesia with pentobarbital given IV (20 mg/kg of body weight), anesthesia with halothane gas, and no anesthesia. Mean velocities (+/- SD) were 3.7 +/- 1.4 mm/min in dogs anesthetized with pentobarbital, 4.3 +/- 2.5 mm/min in dogs anesthetized with halothane, and 3.4 +/- 1.7 mm/min in awake dogs. The differences between the 3 anesthetic conditions were not significant at the P less than 0.05 level. Use of anesthesia at a light surgical plane provides a controlled method for measurement of clearance of nasal mucus with minimal alterations from the nonanesthetized state.     

Acute response of urine pH following ammonium chloride administration to dogs

To test the acidifying ability of the distal portion of the nephrons in healthy dogs, 0.2 g of NH4Cl/kg of body weight was given PO. Samples for venous blood gas analysis and urine pH were taken hourly for 6 hours. Systemic acidemia developed, as evidenced by a statistically significant (P less than 0.05) decrease in blood pH 1 hour after NH4Cl administration. Four hours after administration, mean urine pH decreased to a low of 5.16 +/- 0.1 and was less than 5.5 3 hours after administration. Changes in urine pH 2 hours after administration were statistically significant (P less than 0.05). In human beings, NH4Cl loading is used to detect patients with distal renal tubular acidosis (defective hydrogen ion secretion by the distal nephrons) and normal acid/base values. Distal renal tubular acidosis is diagnosed if urine pH fails to decrease to less than 5.5 after NH4Cl administration. On the basis of the findings of this study, a similar value would be valid for dogs.     

Evaluation of a combined transcutaneous carbon dioxide pressure and pulse oximetry sensor in adult sheep and dogs

OBJECTIVE: To evaluate a combined transcutaneous carbon dioxide pressure (tcPCO(2)) and pulse oximetry sensor in sheep and dogs. ANIMALS: 13 adult sheep and 11 adult dogs. PROCEDURES: During inhalation anesthesia, for the first 10 minutes following sensor placement, arterial blood gas was analyzed and tcPCO(2) was recorded every 2 minutes. Subsequently, the animals were hyper-, normo-, and hypoventilated. The simultaneously obtained tcPCO(2) and PaCO(2) values were analyzed by use of Bland-Altman statistical analysis. RESULTS: Mean +/- SD overall difference between tcPCO(2) and PaCO(2) 10 minutes after sensor application was 13.3 +/- 8.4 mm Hg in sheep and 8.9 +/- 12 mm Hg in dogs. During hyper-, normo-, and hypoventilation, mean difference (bias) and precision (limits of agreement [bias +/- 2 SD]) between tcPCO(2) and PaCO(2) values were 13.2 +/- 10.4 mm Hg (limits of agreement, -7.1 and 33.5 mm Hg) in sheep and 10.6 +/- 10.5 mm Hg (limits of agreement, -9.9 and 31.2 mm Hg) in dogs, respectively. Changes in PaCO(2) induced by different ventilation settings were detected by the tcPCO(2) sensor with a lag (response) time of 4.9 +/- 3.5 minutes for sheep and 6.2 +/- 3.6 minutes for dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The tcPCO(2) sensor overestimated PaCO(2) in sheep and dogs and followed changes in PaCO(2) with a considerable lag time. The tcPCO(2) sensor might be useful for noninvasive monitoring of changes but cannot be used as a surrogate measure for PaCO(2).     

Clinical evaluation of glomerular function: 24-hour creatinine clearance in dogs.

Methods of renal clearance to measure glomerular filtration rate (GFR) were compared with plasma creatinine concentration in clinically normal and partially nephrectomized dogs. Glomerular filtration rate was measured by use of a simple 24-hour creatinine clearance method in 36 normal female Beagles. Mean values were 57.6 +/- 9.3 ml/minute/m2 of body surface or 3.7 +/- 0.77 ml/minute/kg of body weight. Variability of this measurement was considerable, as determined in 4 dogs studied on 4 consecutive days. Glomerular filtration rate was measured in the same 36 dogs while they were under anesthesia, using short clearance periods to compare inulin and endogenous creatinine clearance. Mean values for inulin were 41.8 +/- 13.9 ml/minute/m2 of body surface. A close agreement with creatinine clearance was found (correlation coefficient, 0.998). Mean plasma creatinine concentration was 0.82 (range, 0.5--1.0) mg/100 ml. The value of GFR measurement compared with plasma creatinine concentration was determined in 10 dogs after 75% nephrectomy. Sixty days after partial nephrectomy, GFR was reduced to 61% of normal. Mean plasma creatinine and blood urea nitrogen were 1.2 +/- 0.14 mg/100 ml and 20.4 +/- 7.1 mg/100 ml, respectively. Thus, the detection of reduced renal function may be uncertain when plasma creatinine or blood urea nitrogen are used as a means of evaluating renal function. It was concluded that a simple method of creatinine clearance is a sensitive and useful measurement to detect early or borderline reduction in glomerular function.     

Comparison of the techniques of evaluation of urine dilution/concentration in the dog

The objective of this study was to evaluate the quality of the measurement of dog urine dilution/concentration by comparing osmolality with three methods of specific gravity (USG) measurement, i.e. weighing, refractometry and test strips. In unselected urine samples from 182 dogs there was a better agreement between osmolality and USG determination by refractometry (r = 0.92) than by weighing (r = 0.82) or by test strips (r = 0.27). There was an almost linear relationship between osmolality and USG: osmolality (mOsm/kg) = 36646(34318/38974) x (USGref - 1) + 25(-39/88); calculated osmolality differed from measured osmolality by more than 500 mOsm/kg in only 8 of 181 samples. There was a good agreement between USG determination by weighing and refractometry: USGref = 1.000(0.905/1.095) x USGweighing - 0.0004(-0.0019/0.0027), with a moderate bias. Only 12% of the differences between the two methods exceeded 0.010. Test strip assessment of USG was unreliable because of systematic underestimation and should not be used for dog urine. Refractometry is the best technique for routine evaluation of urine concentration/dilution when osmometry is not available.     

Retrograde flow of spermatozoa into the urinary bladder of dogs during ejaculation or after sedation with xylazine

Retrograde flow of spermatozoa into the urinary bladder of dogs during ejaculation or after administration of xylazine was examined. In experiment 1, the mean (+/- SD) spermatozoal concentration in urine collected by cystocentesis before ejaculation was 0.322 +/- 0.645 X 10(6)/ml. After ejaculation, motile spermatozoa were present in the urine collected by cystocentesis from 12 of 15 dogs, and the concentration of spermatozoa in the urine (5.139 +/- 7.014 X 10(6)/ml) was higher (P less than 0.025) than the concentration in the urine collected before ejaculation. The percentage of the total number of spermatozoa that were displaced during ejaculation and flowed into the urinary bladder (retrograde flow) ranged from 0 to 99.75% (24.67 +/- 33.98%). In experiments 2 and 3, administration of xylazine to sexually rested dogs induced retrograde flow of spermatozoa into the urinary bladder. In experiment 2, all dogs had spermatozoa in urine collected after xylazine administration, with motile spermatozoa present in the urine from 9 of 10 dogs. In experiment 3, urine collected from dogs before administration of xylazine was azoospermic or contained few, nonmotile spermatozoa (0.063 +/- 0.135 X 10(6)/ml), whereas urine collected after administration of xylazine had more (P less than 0.025) and motile spermatozoa (3.717 +/- 4.273 X 10(6)/ml). In experiment 4, administration of xylazine to dogs after ejaculation did not increase the concentration of spermatozoa in the urine. Results indicate that spermatozoa flow into the urinary bladder of dogs during ejaculation or after administration of xylazine to sexually rested dogs.     

Effects of urine alkalization and activated charcoal on the pharmacokinetics of orally administered carprofen in dogs

OBJECTIVE: To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs. ANIMALS: 6 neutered male Beagles. PROCEDURES: Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test. RESULTS: Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean +/- SD maximum concentration was 85.9 +/- 11.9 mg/L and 58.1 +/- 17.6 mg/L, and area under the time-concentration curve was 960 +/- 233 mg/L x h and 373 +/- 133 mg/L x h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.     

USE OF CONTRAST HARMONIC ULTRASOUND FOR THE DIAGNOSIS OF CONGENITAL PORTOSYSTEMIC SHUNTS IN THREE DOGS

Contrast harmonic ultrasound was used to determine macrovascular and perfusion patterns in three dogs with congenital extrahepatic solitary portosystemic shunts (PSS). With coded harmonic angiographic ultrasound, the size and tortuosity of the hepatic arteries were subjectively increased. Single pulse intermittent low-amplitude harmonic perfusion imaging provided contrast enhancement time-intensity curves from regions of interest in the liver. Mean (+/- standard deviation) peak perfusion times of dogs with PSS were significantly shorter (p = 0.01; 7.0 +/- 2.0 s) than reported in normal dogs (22.8 +/- 6.8 s). The contrast inflow slope for the dogs with PSS (14.6 +/- 3.7 pixel intensity units [PIU] was significantly (p = 0.05) larger than reported for normal dogs (3.6 +/- 1.4 PIU/s). These results indicate that combined coded harmonic angiographic and contrast harmonic perfusion sonography can be used to detect increased hepatic arterial blood flow as an indicator of PSS in dogs.     

Plasma pharmacokinetics and tissue fluid concentrations of meropenem after intravenous and subcutaneous administration in dogs

OBJECTIVE: To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device. RESULTS: Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 +/- 0.07 hours, 0.372 +/- 0.053 L/kg, and 6.53 +/- 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 +/- 0.57 hours. Half-life after SC administration was 0.98 +/- 0.21 and 1.31 +/- 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 microg/mL.     

Clinical availability of urinary N-acetyl-beta-D-glucosaminidase index in dogs with urinary diseases

Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was examined in healthy dogs and dogs with urinary diseases, and its clinical usefulness as an indicator of urinary diseases was discussed. Twenty-eight healthy dogs and 20 dogs with urinary diseases were used. Urinary NAG activity was measured using p-nitrophenyl N-acetyl-beta-D-glucosaminide as substrate, and expressed as units per gram of urinary creatinine (NAG index). Urinary NAG index in urine of healthy dogs was 3.2+/-2.4 U/g, and NAG index in the dogs with chronic renal failure or lower urinary tract infection accompanied by pyelonephritis was higher than that in healthy dogs. However, the dogs with lower urinary tract infection without pyelonephritis showed normal values of NAG index. Some dogs with diabetic mellitus showed elevated values of NAG index when control of blood sugar was not successful. Increase of NAG index was observed in some dogs with pyometra before increases of BUN and serum creatinine concentration. Therefore, NAG index in urine seems to be a good indicator for urinary diseases in dogs.     

Susceptibility of bacteria from feline and canine urinary tract infections to doxycycline and tetracycline concentrations attained in urine four hours after oral dosage

OBJECTIVES: To measure urinary concentrations of doxycycline in cats and dogs and tetracycline in dogs 4 h after conventional oral dosing and determine whether these antibiotics were present in sufficient concentrations to be effective against common feline and canine urinary tract pathogens as assessed in vitro by Epsilometer and disc diffusion antimicrobial susceptibility methods. DESIGN: A prospective study involving oral administration to clinically normal cats and dogs of doxycycline or tetracycline (dogs only) and culture of bacteria from dogs and cats with urinary tract infections to determine their susceptibility to both doxycycline and tetracycline in vitro. PROCEDURE: In the first study, nine cats and eight dogs were administered doxycycline monohydrate (5 mg/kg every 12 h) and a further eight dogs were administered tetracycline hydrochloride (20 mg/kg every 8 h) for 72 h. Blood was collected at 2 and 4 h, and urine at 4 h, after the last dose. The concentration of each agent in serum and urine was determined by modified agar diffusion. In the second study, 45 urine samples from cats and dogs with urinary tract infections were cultured. Every bacterial isolate was tested in vitro using both Epsilometer (doxycycline and tetracycline) and disc diffusion (doxycycline, tetracycline or amoxycillin-clavulanate) tests. RESULTS: Serum doxycycline concentrations in sera of cats and dogs at 2 h were 4.2 +/- 1.0 mg/mL and 3.4 +/- 1.1 mg/mL, respectively. The corresponding concentrations at 4 h were 3.5 +/- 0.7 mg/mL and 2.8 +/- 0.6 mg/mL. Urinary doxycycline concentrations at 4 h (53.8 +/- 24.4 mg/mL for cats and 52.4 +/- 24.1 mg/mL for dogs) were substantially higher than corresponding serum values. Serum tetracycline concentrations in dogs at 2 and 4 h, and in urine at 4 h, were 6.8 +/- 2.8, 5.4 +/- 0.8, 144.8 +/- 39.4 mg/mL, respectively. Most of the urinary tract pathogens (35/45) were susceptible to urinary concentrations of doxycycline and 38/45 were susceptible to tetracycline. In contrast 41/45 of all isolates were susceptible to amoxycillin-clavulanate. CONCLUSION: This is the first report of urinary concentrations of doxycycline after conventional oral administration. Concentrations attained in the urine of normal cats and dogs were sufficient to inhibit the growth of a significant number of urinary tract pathogens and thus doxycycline may be a useful antimicrobial agent for some urinary tract infections.     

Clinical investigation of a point-of-care blood ammonia analyzer

BACKGROUND: Hyperammonemia has frequently been implicated in the pathogenesis of hepatic encephalopathy. Blood ammonia determination requires minimal delay between sampling and analysis for accurate results. OBJECTIVES: The aim of this study was to investigate the PocketChem BA, a new point-of-care (POC) blood ammonia analyzer for clinical use by determining machine precision, linearity, repeatability, and accuracy. METHODS: Coefficients of variation were determined by repeated measurement of 2 control solutions. Linearity was investigated by testing serial dilutions of a stock solution. For accuracy, samples from clinical cases were used to compare the results on the PocketChem BA with those obtained using an enzymatic reference method for canine plasma. Canine and feline patients were consecutively enrolled if blood ammonia was assayed and samples could be analyzed shortly after collection. Classification of results (as normal or high, using 100 micromol/L as a cutoff value), Bland-Altman and Deming regression plots, and intraclass correlation coefficients were used to compare the methods. Stability of samples and test strips also was assessed over time. RESULTS: Coefficients of variation were 10.6% and 4.8% for low and high controls, respectively. Concentrations of ammonia in diluted stock solutions correlated positively with mean measured concentrations (Pearson coefficient 0.988, P<.001). Of the 54 samples obtained from 38 dogs and 4 cats, 41 had ammonia concentrations within the readable range. Results from the POC analyzer and the reference method were correlated positively (intraclass coefficient 0.800, 95% confidence interval 0.655-0.888), with the POC analyzer having negative constant and proportional biases. The methods agreed in the classification of 45/54 (83.3%) samples, with 7 false negative results on the POC analyzer. Results of repeated sample and strip analyses at 1 and 24 hours were significantly different (P<.05) from those at 0 hour. CONCLUSIONS: The PocketChem BA has acceptable precision, adequate linearity, and satisfactory agreement with a reference method, but negative constant and proportional biases. The POC analyzer may be suitable for clinical use in patients suspected of having hepatic encephalopathy, using a lower reference limit of 60 mumol/L to decrease false negative results.