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- Author or Editor: Shelly L. Vaden x
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SUMMARY
Pharmacokinetic variables were calculated from time-concentration data obtained after iv (10 mg/kg of body weight; n = 9) and oral (12.5 mg/kg to group A [n = 3]; 25 mg/kg to group B [n = 3]; and 50 mg/kg to group C [n = 3] pigs) cyclosporine (formerly, cyclosporine A) administration. Resulting mean (± sd) pharmacokinetic variables were as follows: half life of distribution, 0.96 (± 0.7) hours; half life of elimination, 7.71 (± 2.6) hours; volume of distribution at steady state, 4.47 (± 2.22) L/ kg; volume of the central compartment, 1.71 (± 0.78) L/ kg; and systemic clearance, 8.95 (± 2.7) ml/kg/min. Oral bioavailability was: overall 57 (± 19) %; group A, 44 (± 11) %; group B, 78 (± 15) %; group C, 48 (± 6) %. Time to peak concentration was 3.55 (± 0.88) hours. During the 22 days of daily oral cyclosporine administration, blood 24-hour trough concentrations were: group A, 224.3 (± 78.4) ng/ml; group B, 640.7 (± 174.6) ng/ml; and group C, 2,344 (± 1,095) ng/ml. Lymphoblast transformation stimulation index was suppressed in all pigs except 1, which had a corresponding cyclosporine concentration of 92.4 ng/ml. Minimal, although statistically significant, decreases in serum albumin and magnesium concentrations and increases in serum creatinine and urea nitrogen concentrations were evident in pigs of some treatment groups. Histologic examination of necropsy specimens revealed mild hepatic necrosis (n = 1 pig), renal tubular dilatation (n = 5), and pulmonary inflammation (n = 2). Pigs given 25 and 50 mg of cyclosporine/kg failed to gain weight.
Abstract
Case Description—A 1-year-old spayed female mixed-breed dog was evaluated because of urinary incontinence, polyuria, polydipsia, and minimally concentrated urine.
Clinical Findings—Markedly high circulating alanine transaminase activity, mildly high circulating alkaline phosphatase activity, and low urine specific gravity were detected for the dog. Results of ultrasonographic examination of the abdomen and cytologic examination of liver samples were unremarkable. Carprofen was detected in serum and plasma samples obtained from the dog. Exposure to carprofen was attributed to ingestion of feces of another dog in the household that was receiving the drug daily.
Treatment and Outcome—Access to feces of other dogs in the household was prevented; no other treatment was initiated. Urinary incontinence, polyuria, and polydipsia resolved, and urine specific gravity increased within 7 days following discontinuation of consumption of feces. Alanine transaminase activity was substantially lower than the value determined during the initial examination, and alkaline phosphatase activity was within the reference range 5 weeks after discontinuation of consumption of feces by the dog.
Clinical Relevance—Findings for the dog of this report suggested that carprofen toxicosis can be caused by consumption of feces of another dog receiving the drug. This cause of adverse effects should be a differential diagnosis for dogs with clinical signs and clinicopathologic abnormalities consistent with carprofen toxicosis.
Abstract
Objective—To evaluate perinuclear anti-neutrophilic cytoplasmic autoantibody (pANCA) status in Soft Coated Wheaten Terriers (SCWTs) and SCWT-Beagle crossbred dogs and to correlate pANCA status of dogs with clinicopathologic variables of protein-losing enteropathy (PLE), protein-losing nephropathy (PLN), or both.
Animals—13 SCWTs and 8 SCWT-Beagle crossbred dogs in a research colony and a control group comprising 7 dogs with X-linked hereditary nephropathy and 12 healthy SCWTs > 9 years old.
Procedures—Samples were obtained from dogs in the research colony every 6 months. At each sample-collection time point, serum concentrations of albumin, globulin, creatinine, and urea nitrogen; fecal concentration of α-proteinase inhibitor; and urinary protein-to-creatinine ratios were determined and correlated with pANCA status.
Results—20 of 21 dogs in the research colony had positive results for pANCAs at a minimum of 2 time points, and 18 of 21 dogs had definitive evidence of disease. None of the control dogs had positive results for pANCAs. A positive result for pANCAs was significantly associated with hypoalbuminemia, and pANCAs preceded the onset of hypoalbuminemia on an average of 2.4 years. Sensitivity and specificity for use of pANCAs to predict development of PLE or PLN were 0.95 (95% confidence interval, 0.72 to 1.00) and 0.8 (95% confidence interval, 0.51 to 0.95), respectively.
Conclusions and Clinical Relevance—Most dogs in this study affected with PLE, PLN, or both had positive results for pANCAs before clinicopathologic evidence of disease was detected. Thus, pANCAs may be useful as an early noninvasive test of disease in SCWTs.
Abstract
Objective—To evaluate the use of dipstick, sulfosalicylic acid (SSA), and urine protein-tocreatinine ratio (UP:C) methods for use in detection of canine and feline albuminuria.
Design—Evaluation study.
Sample Population—599 canine and 347 feline urine samples.
Procedures—Urine was analyzed by use of dipstick, SSA, and UP:C methods; results were compared with those for a species-specific ELISA to determine sensitivity, specificity, positive predictive value (PPV), negative predictive value, and positive and negative likelihood ratios.
Results—Positive results for dipstick and SSA tests (trace reaction or greater) in canine urine had moderate specificity (dipstick, 81.2%; SSA, 73.3%) and poor PPV (dipstick, 34.0%; SSA, 41.8%). Values improved when stronger positive results (≥ 2+) for the dipstick and SSA tests were compared with ELISA results (specificity, 98.9% and 99.0% for the urine dipstick and SSA tests, respectively; PPV, 90.7% and 90.2% for the dipstick and SSA tests, respectively). Data obtained for cats revealed poor specificity (dipstick, 11.0%; SSA, 25.4%) and PPV (dipstick, 55.6%; SSA, 46.9%). Values improved slightly when stronger positive test results (≥ 2+) were used (specificity, 80.0% and 94.2% for the dipstick and SSA tests, respectively; PPV, 63.5% and 65.2% for the dipstick and SSA tests, respectively). The UP:C had high specificity for albuminuria in dogs and cats (99.7% and 99.2%, respectively) but low sensitivity (28.7% and 2.0%, respectively).
Conclusions and Clinical Relevance—Caution should be used when interpreting a positive test result of a dipstick or SSA test for canine or feline albuminuria.
SUMMARY
Objective
To determine usefulness of carbamylated hemoglobin (CarHb) concentration for differentiation of acute renal failure (ARF) from chronic renal failure (CRF) in dogs.
Sample Population
Samples from dogs with ARF or CRF and from nonazotemic control dogs.
Procedure
CarHb concentration was determined in heparinized blood samples by measuring the micrograms of valine hydantoin (VH) per gram of hemoglobin (Hb), using a high-performance liquid chromatography assay, in which carbamyl valine is converted to VH via acid hydrolysis.
Results
CarHb concentration was significantly higher in dogs with ARF and CRF, compared with values in control dogs (ARF vs control, P < 0.05; CRF vs control, P < 0.001). Furthermore, CarHb concentration was significantly (P < 0.001) higher in dogs with CRF, compared with that in dogs with ARF. Carbamylated hemoglobin concentration did not correlate with serum urea nitrogen or creatinine concentration. Using a cutoff value of 100 μg of VH/g of Hb, the sensitivity and specificity of CarHb concentration for differentiating ARF from CRF was 96.1 and 84.2%, respectively.
Conclusions
CarHb concentration was useful in the differentiation of ARF from CRF in the dogs of this study.
Clinical Relevance
CarHb concentration may be used to increase the accuracy of identifying ARF, so that early, aggressive management can be instituted, thereby increasing the chance of recovery. (Am J Vet Res 1997;58:1193–1196)
Summary
Outcome of and complications associated with bilateral adrenalectomy in 8 cats with pituitary-dependent hyperadrenocorticism and bilateral adrenocortical hyperplasia and outcome of and complications associated with unilateral adrenalectomy in 2 cats with adrenocortical tumor (adrenocortical adenoma, 1 cat; adrenocortical carcinoma, 1 cat) and unilateral adrenomegaly were determined. Glucocorticoids were administered to all cats at the time of surgery, and mineralocorticoids were administered to the 8 cats that underwent bilateral adrenalectomy. A ventral midline celiotomy was performed in all cats.
Intraoperative complications did not develop in any cat. Postoperative complications developed in all cats and included abnormal serum electrolyte concentrations (n = 8), skin lacerations (n = 5), pancreatitis (n = 3), hypoglycemia (n = 2), pneumonia (n = 1), and venous thrombosis (n = 1). Three cats died within 5 weeks after surgery of complications associated with sepsis (n = 2) or thromboembolism (n = 1). Clinical signs and physical abnormalities caused by hyperadrenocorticism resolved in the remaining 7 cats 2 to 4 months after adrenalectomy. Insulin treatment was discontinued in 4 of 6 cats with diabetes mellitus. Median survival time for these 7 cats was 12 months (range, 3 to > 30 months). Two cats died of acute adrenocortical insufficiency 3 and 6 months after bilateral adrenalectomy, 2 cats were euthanatized because of chronic renal failure 3 and 12 months after bilateral (n = 1) or unilateral (n = 1) adrenalectomy, and 2 cats were alive 9 and 14 months after bilateral adrenalectomy. In the remaining cat, clinical signs recurred 10 months after the cat had undergone unilateral adrenalectomy. The remaining adrenal gland was found to contain an adrenocortical adenoma and was removed. The cat was doing well when it was lost to follow-up 15 months after the second surgery.
Abstract
Objective—To evaluate intestinal permeability and gluten sensitivity in a family of Soft-Coated Wheaten Terriers (SCWT) affected with protein-losing enteropathy (PLE), protein-losing nephropathy (PLN), or both.
Animals—6 affected adult dogs.
Procedure—Intestinal biopsy specimens, urine protein- to-creatinine ratio, serum concentrations of albumin and globulin, and concentration of α1-protease inhibitor in feces were evaluated before, during, and 13 weeks after daily administration of 10 g of gluten for 7 weeks. Eosinophils and lymphocytes-plasmacytes were enumerated in intestinal biopsy specimens. Intestinal permeability was evaluated before and during the sixth week of gluten administration via cellobiose-mannitol and chromium-EDTA absorption tests.
Results—Serum globulin concentration decreased significantly after prolonged administration of gluten. Although not significant, there was an increase in lymphocytes- plasmacytes and a decrease in eosinophils in intestinal biopsy specimens. Furthermore, these counts were greater than those reported for clinically normal dogs. Gluten administration did not increase intestinal permeability.
Conclusions and Clinical Relevance—Daily administration of gluten was associated with a significant decrease in serum globulin concentration in SCWT affected with PLE or PLN, but other variables remained unchanged. Although enhanced wheatgluten sensitivity may be one factor involved in the pathogenesis of PLE or PLN in SCWT, this syndrome does not appear to be the result of a specific sensitivity to gluten. (Am J Vet Res 2000;61:518–524)
