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Biomedical subjects

Kenneth R Harkin

Publications and source records attributed to Kenneth R Harkin.

13 recordsLinked to original sources

Sensory and motor neuropathy in a Border Collie.

A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation.

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Development and evaluation of a flow cytometry microsphere assay to detect anti-histone antibody in dogs.

Anti-nuclear antibody (ANA) is one of the diagnostic parameters that support a diagnosis of autoimmune disorders in humans, dogs, and horses, particularly the condition systemic lupus erythematosus (SLE). The most commonly used method for detecting ANA in canine serum is the indirect immunofluorescence antibody assay (IFA) that detects dog IgG with reactivity towards mammalian cell nuclei. Interpretation of the IFA results is very subjective and dependent on the source of tissue/cellular substrate. We have developed a flow cytometry based assay to detect canine serum antibodies specific to histones. Histones were chosen as the target antigen because these nuclear proteins are the most common nuclear substrate for ANA in dogs with SLE. Microsphere beads were coated with histones and incubated with canine sera. Bound anti-histone antibodies were detected by FITC-conjugated rabbit F(ab')2 anti-dog IgG. Sera from four groups of dogs (47 dogs total) were tested for anti-histone antibodies and compared with the traditional IFA assay. The groups included 15 healthy dogs, 15 dogs with noninflammatory diseases, 9 dogs with polyarthritis and positive ANA, and 8 German shepherds with perianal fistulas. The microsphere assay results indicated that only one dog in the noninflammatory group and four out of nine dogs in the polyarthritis group had mean fluorescent intensity values above our established cut-off (defined as 2 S.D. above the mean of healthy controls). There was moderate agreement between the anti-histone assay and the traditional ANA (kappa statistic=0.54). Absorption of ANA positive serum with total histones dramatically diminished the fluorescent signal detected by flow cytometry and the speckled nuclear pattern observed by IFA, whereas preabsorption did not change the diffuse nuclear staining pattern. These findings indicate that the anti-histone assay will not replace the ANA test and that other nuclear proteins, such as ribonucleoproteins may contribute to the diffuse ANA patterns.

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Glomerulocystic kidney disease in a kitten.

A 4-month-old 1-kg female Siamese-Manx cross kitten was evaluated because of renomegaly and renal failure. Ultrasonography and cytologic examination of a renal aspirate failed to provide an antemortem diagnosis. Histologic lesions included diffuse cystic dilatation of all tubules and Bowman's spaces in the renal cortex and occasional small glomerular tufts; the lesions were similar to those of glomerulocystic kidney disease of humans. Glomerulocystic kidney disease is a rare cause of early-onset renal failure, but should be considered when renomegaly is detected, cysts are not detected in the kidney by ultrasonography, and cytologic examination of a renal aspirate is nondiagnostic.

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Clinical application of a polymerase chain reaction assay for diagnosis of leptospirosis in dogs.

OBJECTIVE: To evaluate the use of a polymerase chain reaction (PCR) assay on urine samples for diagnosis of leptospirosis in dogs. DESIGN: Prospective case study. ANIMALS: 132 dogs with clinical signs suggestive of leptospirosis and 13 healthy dogs. PROCEDURE: PCR testing was performed on urine samples to detect leptospiral DNA; results were compared with results of conventional criteria for the diagnosis of leptospirosis. RESULTS: Leptospirosis was diagnosed in 8 dogs via established criteria; all these dogs had positive results of PCR assay, including 1 dog with positive results before seroconversion developed. A positive PCR assay result was also obtained in 16 dogs that did not have a confirmed diagnosis of leptospirosis. In the 8 dogs that had a confirmed diagnosis of leptospirosis, serovars pomona (n = 3 dogs), grippotyphosa (2), canicola (2), and bratislava (1) were identified serologically. The remaining 121 dogs all had a diagnosis other than leptospirosis or were healthy. For PCR testing on urine, sensitivity was 100%, specificity was 88.3%, positive predictive value was 33%, and negative predictive value was 100%. CONCLUSIONS AND CLINICAL RELEVANCE: Positive PCR test results prior to seroconversion may have value in establishing an early diagnosis. Positive results in dogs that had signs consistent with leptospirosis despite failing to meet established criteria for leptospirosis raise questions regarding the sensitivity of serologic testing in diagnosis of leptospirosis. Serovars pomona, grippotyphosa, and canicola were most common.

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Comparison of polymerase chain reaction assay, bacteriologic culture, and serologic testing in assessment of prevalence of urinary shedding of leptospires in dogs.

OBJECTIVE: To compare results of polymerase chain reaction (PCR) testing of urine samples, serologic testing, and bacteriologic culture of urine to determine prevalence of urinary shedding of leptospires in dogs. DESIGN: Serial case study. ANIMALS: 500 dogs evaluated serially without regard to health status. PROCEDURE: Urine samples were examined via PCR assay and bacteriologic culture for leptospires. Blood samples were analyzed for antibodies against serovars canicola, bratislava, pomona, icterohemorrhagiae, grippotyphosa, and hardjo. RESULTS: Titers > or = 1:100 against at least 1 serovar were detected in 104 (20.8%) dogs, and titers > or = 1:400 were detected in 41 (8.2%) dogs. High titers were detected most commonly to serovar grippotyphosa, followed by icterohemorrhagiae, canicola, pomona, bratislava, and hardjo. High titers to > 1 serovar were detected in 14 dogs. A positive PCR assay result was obtained in 41 (8.2%) dogs, only 9 of which had a titer > or = 1:100. Leptospires were not cultured from the urine of any dog. Only 4 dogs had clinical leptospirosis. Overall disease prevalence was 0.8% for the 6-month evaluation period. Compared with PCR assay, serologic testing for predicting shedding had a sensitivity of 22%, specificity of 79%, positive predictive value of 9%, and negative predictive value of 92%. CONCLUSIONS AND CLINICAL RELEVANCE: Irrespective of health status, 8.2% of dogs were shedding pathogenic leptospires. Serologic testing was a poor predictor of urinary shedding. Clinically normal dogs that shed leptospires may pose a zoonotic risk to their owners.

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Dysautonomia in dogs: 65 cases (1993-2000).

OBJECTIVE: To determine signalment, history, clinical findings, results of autonomic function testing and other antemortem diagnostic tests, and pathologic findings in dogs with dysautonomia. DESIGN: Retrospective study. ANIMALS: 65 dogs with dysautonomia. PROCEDURE: Case records of 68 dogs with a diagnosis of dysautonomia were reviewed; inclusion criteria included histologic confirmation of dysautonomia or clinical signs and results of pharmacologic testing consistent with dysautonomia. RESULTS: 65 dogs fulfilled all criteria for dysautonomia. Dogs from rural environments were overrepresented, and cases of dysautonomia were reported for every month, although the highest number of cases was reported in February and March. Vomiting was the most common clinical sign, followed by diarrhea, signs of anorexia and depression, weight loss, and dysuria. The most common physical examination finding was decreased or absent anal tone, followed by absent pupillary light reflexes and elevated nictitating membrane. Results of pharmacologic testing were consistent with dysautonomia, although no single test was 100% sensitive. Histologic lesions consistent with dysautonomia were found in the autonomic ganglia, brainstem nuclei, and ventral horns of the spinal cord. CONCLUSIONS AND CLINICAL RELEVANCE: Dysautonomia is an endemic disease in Kansas, and a high index of suspicion of the disease can be made by combining clinical signs, physical examination findings, and results of pharmacologic testing.

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Concurrent administration of water-soluble vitamin E can increase the oral bioavailability of cyclosporine a in healthy dogs.

Randomized crossover studies were performed to determine the effect of coadministration of d-alpha-tocopheryl polyethylene glycol 1,000 succinate (vitamin E TPGS) on the oral bioavailability of cyclosporine A (CsA) formulated as either Sandimmune (Novartis Pharmaceuticals) or Neoral (Novartis Pharmaceuticals). Healthy dogs were given a single oral dose of each cyclosporine formulation with and without vitamin E TPGS. Blood samples were collected from each dog before and at various intervals for 24 hours after drug administration. Whole-blood CsA concentrations were determined by high-pressure liquid chromatography. Noncompartmental pharmacokinetic analysis showed that coadministration of vitamin E TPGS increased the oral bioavailability of Sandimmune. The bioavailability of Neoral was greater than that of cyclosporine. Concurrent administration of vitamin E TPGS had no consistent effect on the bioavailability of Neoral.

Administration, Oral↗

Postoperative rupture of an aortic aneurysmal dilation associated with a patent ductus arteriosus in a dog.

OBJECTIVE: To describe an unusual case of fatal aortic aneurysm rupture after standard ligation of a left-to-right shunting patent ductus arteriosus (PDA) and review the literature concerning the causes of aneurysm and applicable medical physics of blood flow that may contribute to mural failure. STUDY DESIGN: Clinical case report. SAMPLE POPULATION: An 11-month-old female Brittany spaniel. RESULTS: A PDA was diagnosed in the dog after referral for a grade IV/IV cardiac murmur. Diagnostic tests performed included a minimum database, thoracic radiography, and echocardiography. Conventional surgical ligation of the PDA was performed. The postoperative recovery from anesthesia was uneventful. Approximately 5 hours after surgery, the dog vocalized once and collapsed. All resuscitative efforts failed. Necropsy showed a large, spiral rupture of the cranial and dorsal wall of the aorta that extended from the left subclavian artery to 2 cm distal to the PDA-aorta junction. No evidence of intramural, perianeurysmal hemorrhage or inflammation was noted. Histopathologic examination of the ruptured aneurysm showed that the wall lacked a defined tunica intima and endothelial cell layer. A distinct separation of the thinned tunica media parallel to the elastic fibers was noted. CONCLUSIONS AND CLINICAL RELEVANCE: Dilatation of the aorta near the area of a PDA is one of the recognized abnormalities associated with the condition. Aneurysmal dilatation results from and contributes to abnormal blood flow dynamics and increased aortic wall tension, which promotes expansion. Although an unusual and previously unreported sequela, rupture of the aneurysm should be considered a possible complication when ligation of a PDA with a conspicuous aortic aneurysmal dilation is performed.

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Dysautonomia in a family of German shorthaired pointers.

Four, 5-week-old German shorthaired pointers from a litter of five puppies were presented for evaluation of vomiting and diarrhea. The dam was euthanized for suspected dysautonomia, and the fifth puppy died 1 day prior to presentation. On presentation, two puppies had vomiting and diarrhea, and the other two appeared healthy. The results of testing supported the diagnosis of dysautonomia in the two affected puppies but not in the healthy puppies. On day 5 of hospitalization, one apparently healthy puppy developed vomiting and diarrhea and had supportive testing for dysautonomia. Dysautonomia was confirmed at necropsy in affected dogs.

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Hypothyroidism and myocardial failure in two Great Danes.

Two Great Danes were evaluated for signs of congestive heart failure. Dilated cardiomyopathy was diagnosed in each dog. Both dogs were diagnosed concurrently with primary hypothyroidism. Following appropriate supplementation with levothyroxine, both dogs showed significant improvement in myocardial contractility, as demonstrated by increased fractional shortening and reductions in left atrial size, and left ventricular end-systolic and diastolic diameters. These observations suggest that hypothyroidism may lead to myocardial failure in Great Danes that is partially or fully reversible following thyroid hormone replacement therapy, and that hypothyroidism should be considered in all Great Danes presenting with systolic failure.

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Comparison of complications of percutaneous endoscopic versus surgically placed gastrostomy tubes in 42 dogs and 52 cats.

Dogs and cats that had a percutaneous endoscopic gastrostomy (PEG) tube or surgically placed gastrostomy (SPG) tube inserted were retrospectively analyzed to compare complication rates and the severity of complications. Complication rates and severity scores were not significantly different when the PEG tube group was compared to the SPG tube group in either dogs or cats. Only when data from dogs and cats were combined did PEG tubes have a significantly higher complication rate and significantly greater complication severity scores.

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Evaluation of azathioprine on lesion severity and lymphocyte blastogenesis in dogs with perianal fistulas.

Fourteen dogs with perianal fistulas were entered into a prospective clinical study to investigate the effects of long-term azathioprine on clinical outcome and to determine if the clinical results correlated with lymphocyte blastogenesis tests. Complete remission of perianal fistulas was seen in eight (57%) of 14 dogs; partial remission occurred in one (7%) dog; and no response was detected in five (36%) dogs. The results of lymphocyte blastogenesis assays did not correlate with therapeutic response.

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