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- Author or Editor: Nathan L. Dykes x
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Abstract
Objective—To determine whether a carboplatin dose calculation that is based on a targeted area under the concentration-versus-time curve (AUCTarget) and individual glomerular filtration rate (GFR) accurately predicts carboplatin-associated myelotoxicoses in tumor-bearing cats, and to determine the maximum tolerated AUCTarget.
Animals—32 cats with tumors.
Procedures—In each cat, plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid was measured to assess GFR. Carboplatin was administered IV. The dose was calculated by use of an equation as follows: Dose = AUCTarget × 2.6 × GFR × body weight. Initial AUCTarget was 2.0 min·mg·mL−1 and was increased in increments of 0.50 min·mg·mL−1 in cohorts of 3 cats. To assess myelotoxic effects, CBCs were performed weekly for ≥ 4 weeks. Following identification of the maximum tolerated AUCTarget, additional cats were treated at that AUCTarget and plasma platinum concentrations were measured in 6 cats.
Results—The AUCTarget values ranged from 2.0 to 3.0 min·mg·mL−1. Neutropenia was the dose-limiting toxicosis, and the maximum tolerated AUCTarget was 2.75 min·mg·mL−1. Nineteen cats received this dose of carboplatin; 13 became neutropenic, but only 1 developed severe neutropenia (< 500 neutrophils/μL), and none had neutropenia-associated clinical signs. In the cats that had plasma platinum concentration determined, the difference between AUCTarget and the measured value ranged from −0.23 to 0.31 min·mg·mL−1 (median, 0.20 min·mg·mL−1).
Conclusions and Clinical Relevance—In cats, carboplatin-associated myelotoxicoses were accurately and uniformly predicted by use of the proposed dosing strategy. The maximum tolerated AUCTarget for a single dose of carboplatin was 2.75 min·mg·mL−1.
Abstract
Objective—To determine whether a glomerular filtration rate (GFR) assay based on serum iohexol clearance can be used to predict carboplatin clearance in cats.
Animals—10 cats with tumors.
Procedures—GFR was measured concurrently by use of plasma clearance of technetium Tc 99m–labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) to yield GFR99mTc-DTPA and serum clearance of iohexol to yield GFRIohexol. A single dose of carboplatin was administered IV as a bolus. Dose was calculated by use of a target value for the area under the plasma platinum concentration-versus-time curve (AUCTarget) and estimation of platinum clearance (CLPT) derived from GFR99mTc-DTPA as follows: dose = AUCTarget × 2.6 × GFR99mTc-DTPA × body weight, where AUCTarget is 2.75 min·mg·mL−1. Plasma platinum concentrations were measured via atomic absorption spectrophotometry. Values for GFR99mTc-DTPA and GFRIohexol were compared by use of least-squares regression and Bland-Altman analysis. Least-squares regression was used to determine whether CLPT could be predicted from GFR99mTc-DTPA or GFRIohexol (or both).
Results—GFR99mTc-DTPA and GFRIohexol were strongly correlated (r = 0.90), but GFRIohexol values were significantly larger by a factor of approximately 1.4. Platinum clearance had a significant linear relationship to GFR99mTc-DTPA (CLPT = 2.5 × GFR99mTc-DTPA) and to GFRIohexol (CLPT = [1.3 × GFRIohexol] + 1.4).
Conclusions and Clinical Relevance—In cats, serum iohexol clearance was an accurate predictor of CLPT and can be used to calculate the carboplatin dose as follows: dose = AUCTarget × ([1.3 × GFRIohexol] + 1.4) × body weight.
Abstract
Objective—To determine whether sensitivity of detecting an anomalous portosystemic blood vessel during operative mesenteric portography varied with patient positioning.
Design—Retrospective study.
Animals—34 dogs with a portosystemic shunt diagnosed via scintigraphy or surgery.
Procedure—Portograms were evaluated for a portosystemic blood vessel. Sensitivity was calculated from results obtained with dogs in left lateral, right lateral, and dorsal recumbency and from results obtained with dogs in 2 or 3 positions. Differences in sensitivity among positions and between 2 examiners were evaluated.
Results—Sensitivity was 85, 91, and 100% in dorsal, right lateral, and left lateral recumbency, respectively. Sensitivity was lower in dorsal recumbency than in left lateral recumbency, although differences were not significant. There was no significant difference between sensitivity of results obtained in dorsal and right lateral recumbency or right lateral and left lateral recumbency. Sensitivity for combined right lateral and dorsal positions was 97%, which was better than that in dorsal recumbency alone, although the difference was not significant. Because sensitivity in left lateral recumbency was 100%, there was no need to evaluate the improvement obtained by combining the result of this position with the results of other positions.
Conclusion and Clinical Relevance—Results of mesenteric portography varied with patient positioning. The optimal position varied among patients but left lateral recumbency may be better and dorsal recumbency worse. Sensitivity may be improved by performing the test with the patient in orthogonal recumbent positions. (J Am Vet Med Assoc 2001; 219:1251–1253)
Abstract
Objective—To characterize the pharmacokinetic disposition of carboplatin and determine whether glomerular filtration rate (GFR) could be used to predict carboplatin clearance and myelotoxic effects in cats with tumors.
Animals—10 cats with tumors.
Procedure—Glomerular filtration rate was assessed in each cat by monitoring plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Each cat received carboplatin (200 mg/m2 of body surface area) administered as an IV bolus. Plasma platinum concentrations were measured via atomic absorption spectrophotometry, and pharmacokinetic analysis was performed. A CBC was performed weekly for each cat, and the correlation between the area under the concentration-versus-time curve (AUC) and the severity of myelosuppression was calculated. Least squares regression analysis was performed to determine whether GFR could be used to predict plasma platinum clearance (ClPt).
Results—For all cats, AUC measurements ranged from 0.99 to 4.30 min·mg·mL–1. Neutrophil concentration nadirs were detected 1 to 3 weeks after treatment and ranged from 200 to 8,000 cells/µL. The absolute neutrophil concentration at the nadir was inversely correlated with AUC. The ClPt was predicted by use of GFR measurements (ClPt = 2.60 × GFR). A carboplatin dose prescription model was derived involving AUC, estimated ClPt, and body weight in kilograms (BWkg), in which dose = AUC × 2.60(GFR) × BWkg.
Conclusions and Clinical Relevance—In cats, an individualized prescription strategy for carboplatin administration based on a targeted AUC and determination of GFR might more uniformly predict myelosuppression than that predicted by conventional dosing based on body surface area. (Am J Vet Res 2004;65:1502–1507)
Abstract
Objective—To assess agreement between a commercially available Geiger-Meuller (GM) survey meter and millirem tissue-equivalent (TE) meter for measuring radioactivity in cats treated with sodium iodine I 131 (131I).
Animals—15 cats with hyperthyroidism and undergoing 131I treatment.
Procedures—Duplicate measurements were obtained at a distance of 30 cm from the thyroid region of each cat's neck by 2 observers who used both meters on day 3 or 5 after131I administration. Comparisons of measurements between meters and observers were made, with limits of agreement defined as the mean difference ± 2 SDs of the differences.
Results—For observer 1, the mean of the differences in the 2 meters' measurements in all cats was 0.012 mSv/h (SD, 0.011 mSv/h). For observer 2, the mean of the differences in measurements was 0.012 mSv/h (SD, 0.010 mSv/h). For the GM meter, the mean of the differences of the 2 observers for all cats was 0.003 mSv/h (SD, 0.011 mSv/h). For the TE meter, the mean of the differences of the 2 observers for all cats was 0.003 mSv/h (SD, 0.007 mSv/h).
Conclusions and Clinical Relevance—Results indicate that there was considerable agreement between meters and observers in measurements of radioactivity in cats treated with 131I. Measurements obtained by use of the GM meter may be approximately 0.01 mSv/h less than or 0.03 mSv/h higher than those obtained with the TE meter. If this range is acceptable for an institution's release criteria, the 2 meters should be considered interchangeable and acceptable for clinical use.
Abstract
Objective—To compare the bone mineral density (BMD) of the proximal portion of the femur in dogs with and without early osteoarthritis secondary to hip dysplasia.
Animals—24 dogs (3 Greyhounds, 6 Labrador-Greyhound crossbreeds, and 15 Labrador Retrievers).
Procedure—Computed tomography (CT) of the pelvis, including a bone-density phantom, was performed for each dog. Centrally located transverse CT slices and a computer workstation were used to identify 16 regions of interest (ROIs) in the proximal portion of the femur. For each ROI, the mean Hounsfield unit value was recorded; by use of the bone-density phantom and linear regression analysis, those values were converted to equivalent BMD (eBMD). Mean eBMD values for the subchondral and nonsubchondral ROIs in dogs with and without osteoarthritis (determined at necropsy) were compared. A mixed-model ANOVA and post hoc linear contrasts were used to evaluate the effects of osteoarthritis, breed, and sex on the BMD value.
Results—At necropsy, osteoarthritis was detected in 14 hip joints in 9 dogs; all lesions included early cartilage fibrillation. After adjusting for breed and sex, eBMD in subchondral ROIs 8 and 12 (adjacent to the fovea) were 8% and 6% higher, respectively, in osteoarthritis-affected dogs, compared with unaffected dogs; in the nonsubchondral ROIs, eBMD was 10% higher in osteoarthritis-affected dogs.
Conclusions and Clinical Relevance—Compared with findings in unaffected dogs, increased eBMD in hip joints of dogs with early osteoarthritis supports a strong relationship between the subchondral and epiphyseal regions and articular cartilage in the pathogenesis and progression of osteoarthritis.
Abstract
Objective—To compare estimation of glomerular filtration rate determined via conventional methods (ie, scintigraphy and plasma clearance of technetium Tc 99m pentetate) and dynamic single-slice computed tomography (CT).
Animals—8 healthy adult cats.
Procedures—Scintigraphy, plasma clearance testing, and dynamic CT were performed on each cat on the same day; order of examinations was randomized. Separate observers performed GFR calculations for scintigraphy, plasma clearance testing, or dynamic CT. Methods were compared via Bland-Altman plots and considered interchangeable and acceptable when the 95% limits of agreement (mean difference between methods ± 1.96 SD of the differences) were ≤ 0.7 mL/min/kg.
Results—Global GFR differed < 0.7 mL/min/kg in 5 of 8 cats when comparing plasma clearance testing and dynamic CT; the limits of agreement were 1.4 and −1.7 mL/min/kg. The mean ± SD difference was −0.2 ± 0.8 mL/min/kg, and the maximum difference was 1.6 mL/min/kg. The mean ± SD difference (absolute value) for percentage filtration by individual kidneys was 2.4 ± 10.5% when comparing scintigraphy and dynamic CT; the maximum difference was 20%, and the limits of agreement were 18% and 23% (absolute value).
Conclusions and Clinical Relevance—GFR estimation via dynamic CT exceeded the definition for acceptable clinical use, compared with results for conventional methods, which was likely attributable to sample size and preventable technical complications. Because 5 of 8 cats had comparable values between methods, further investigation of dynamic CT in a larger sample population with a wide range of GFR values should be performed.
Abstract
Objective—To determine whether dorsolateral subluxation (DLS) scores in young dogs could be used to reliably predict which dogs would develop evidence of hip osteoarthritis and whether DLS scores measured at various ages correlated with each other.
Animals—129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds.
Procedures—DLS scores were measured on radiographs taken at 4, 8, and 12 months of age and at necropsy (8 to 36 months of age). At necropsy, the hip joints were examined macroscopically and a score assigned for degree of cartilage degeneration.
Results—DLS scores at 4 (n = 35, r s = –0.62), 8 (n = 106, r s = –0.54), and 12 (n = 15, r s = –0.87) months of age were significantly correlated with cartilage degeneration scores, and DLS scores at 8 months of age were significantly correlated with scores obtained at the time of necropsy (n = 39, r s = 0.87). The DLS scores at 4 months of age were significantly different from scores at 8 months of age, but scores did not differ significantly thereafter. Likelihood ratios for cartilage lesions for low (< 45%), intermediate (≥ 45 but ≤ 55%), and high (> 55%) DLS scores at 8 months of age were 8.0, 2.6, and 0.2, respectively.
Conclusions and Clinical Relevance—Results suggest that DLS score at 8 months of age was a reasonable, albeit imperfect, predictor of the condition of the hip joint cartilage at necropsy. Thus, the DLS method might be useful for early identification of dogs with hip dysplasia. (Am J Vet Res 2001;62:1711–1715)
Abstract
Objective
To determine whether dorsolateral subluxation (DLS) of the femoral head reflects osseous conformation of the coxofemoral (hip) joint and represents a property distinct from maximum passive laxity of the hip joint in dogs.
Animals
14 Labrador Retrievers, 16 Greyhounds, 58 Greyhound-Labrador Retriever mixed-breed dogs, and 1 Rottweiler.
Procedures
DLS of the femoral head (DLS score) and passive laxity of the hip joint (distraction index) were determined radiographically in 3 groups of dogs: not treated (167 joints of 84 dogs); before and after injecting 2 ml of hyaluronan into 25 hip joints of 13 dogs; and before and after unilateral triple pelvic osteotomy in 5 dogs. Results of the 2 methods were compared for each group.
Results
In untreated dogs, the correlation coefficient (r) of DLS score versus distraction index was −0.73 and −0.69 for 84 left and 83 right hip joints, respectively. Mean coefficient of determination (r 2) for both hips was 0.5. Mean DLS score did not differ before and after intra-articular injection of hyaluronan into either hip joint, whereas mean distraction index increased significantly after intra-articular injection. Unilateral triple pelvic osteotomy resulted in a significant increase in DLS score, compared with values obtained before surgery. However, distraction index before and after surgery did not differ significantly.
Conclusions and Clinical Relevance
The DLS test assesses the congruity of the acetabulum and the femoral head in a canine hip joint and thus represents a characteristic distinct from maximum passive laxity. The DLS score and the distraction index evaluate different components of hip joint stability. (Am J Vet Res 1999;60:1571–1576)
