Late Toxicity and Long-Term Local Control in Patients With Ultra-Central Lung Tumours Treated by Intensity-Modulated Radiotherapy-Based Stereotactic Ablative Body Radiotherapy With Homogenous Dose Prescription.

AIMS: To report late toxicity and long-term outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic ablative body radiotherapy (SABR) in patients with ultra-central lung tumours. MATERIALS AND METHODS: This is a single-institution retrospective analysis of patients treated with SABR for ultra-central tumours between May 2008 and April 2016. Ultra-central location was defined as tumour (GTV) abutting or involving trachea, main or lobar bronchi. Respiratory motion management and static-field dynamic-IMRT were used, with dose prescribed homogeneously (maximum <120%). Descriptive analysis, Kaplan-Meier method, log-rank test and Cox regression were used to assess outcomes. RESULTS: Sixty-five per cent of patients had inoperable primary non-small cell lung cancer and 35% had lung oligometastases. The median age was 72 (range 34-85) years. The median gross tumour volume and planning target volume (PTV) were 19.6 (range 1.7-203.3) cm3 and 57.4 (range 7.7-426.6) cm3, respectively. The most commonly used dose fractionation was 60 Gy in eight fractions (n = 51, 87.8%). Median BED10 for D98%PTV and D2%PTV were 102.6 Gy and 115.06 Gy, respectively. With a median follow-up of 26.5 (range 3.2-100.5) months, fatal haemoptysis occurred in five patients (8.7%), of which two were directly attributable to SABR. A statistically significant difference was identified between median BED3 for 4 cm3 of airway, for patients who developed haemoptysis versus those who did not (147.4 versus 47.2 Gy, P = 0.005). At the last known follow-up, 50 patients (87.7%) were without local recurrence. Freedom from local progression at 2 and 4 years was 92 and 79.8%, respectively. The median overall survival was 34.3 (95% confidence interval 6.1-61.6) months. Overall survival at 2 and 4 years was 55.1 and 41.2%, respectively. CONCLUSION: In patients with high-risk ultra-central lung tumours, IMRT-based SABR with homogenous dose prescription achieves high local control, similar to that reported for peripheral tumours. Although fatal haemoptysis occurred in 8.7% of patients, a direct causality with SABR was evident in only 3%. Larger studies are warranted to ascertain factors associated with outcomes, especially toxicity, and identify patients who would probably benefit from this treatment.

A retrospective study of dogs with atypical hypoadrenocorticism: a diagnostic cut-off or continuum?

OBJECTIVES: To describe the clinicopathologic findings and outcome in dogs with atypical hypoadrenocorticism (Group 1) and dogs with suspected atypical hypoadrenocorticism whose post-adrenocorticotropic hormone stimulation cortisol concentrations were greater than 55 nmol/L but below the laboratory reference interval (Group 2). METHODS: Medical records were searched to identify dogs diagnosed with hypoadrenocorticism between January 2004 and June 2014. Dogs were excluded if their Na:K ratio was less than 27 or if they had received prior therapy that could interfere with adrenocorticotropic hormone stimulation testing. RESULTS: Forty dogs were included in Group 1 and nine dogs in Group 2. In Group 1, the most common biochemical abnormalities were hypoalbuminaemia (87%) and hypocholesterolaemia (76%). Of 35 dogs in Group 1 with follow-up biochemistry results, five (14%) developed electrolyte abnormalities at 2 to 51 months post diagnosis. Of seven dogs in Group 2 with follow-up, glucocorticoid therapy was discontinued in two dogs without return of clinical signs, four dogs were subsequently diagnosed with inflammatory bowel disease and one dog continued to have clinical signs despite glucocorticoid treatment. CLINICAL SIGNIFICANCE: Dogs with gastrointestinal signs and hypoalbuminaemia and, or, hypocholesterolaemia should be evaluated for atypical hypoadrenocorticism. Follow-up electrolyte monitoring is recommended because some will develop electrolyte abnormalities. Although dogs in Group 2 had a clinical presentation compatible with atypical hypoadrenocorticism, the diagnosis appears unlikely based on review of follow-up data. Dogs with equivocal adrenocorticotropic hormone stimulation results should be evaluated for other underlying diseases such as inflammatory bowel disease. The use of endogenous adrenocorticotropic hormone measurements in these dogs warrants investigation.

Presumed primary immune-mediated neutropenia in 35 dogs: a retrospective study.

OBJECTIVES: To describe, in a cohort of dogs with presumed primary immune-mediated neutropenia, the presenting clinical characteristics, haematology results, bone marrow characteristics, therapies used (drugs and doses), clinical response to treatment, relapse and outcome at six months and one year. METHODS: Multi-institutional recruited retrospective descriptive case series with voluntary submissions. Presumed immune-mediated neutropenia was diagnosed based on a neutrophil concentration <1·5×109 cells/L on a minimum of two complete blood counts, exclusion of other causes of neutropenia based on a diagnostic bone marrow aspirate or biopsy, and exclusion of secondary immune-mediated neutropenia. Dogs meeting these diagnostic criteria between 2006 and 2013, and that had a haematocrit of ≥29% and minimum of two complete blood clounts performed after initiation of therapy, were included. RESULTS: Information on 35 dogs was included. Neutropenia was less than 0·5×109 cells/L in most cases (21 dogs), 0·5 to ·99×109 cells/L in 11, and 1.0 to 1·49×109 cells/L in three. Eight dogs had thrombocytopenia, which was severe (<49·9×109 cells/L) in three. [Correction added on 23 May 2017, after first online publication: the cell numbers were incorrect due to errors in the conversion of cell measurements to international units. The numbers have been corrected throughout the article and Table 2.] Twenty-three dogs had myeloid hyperplasia, 10 dogs had myeloid hypoplasia and two dogs had normal myelopoiesis. Neutropenia resolved in 32 of 33 dogs within two weeks of starting corticosteroid therapy and in all dogs within one month. Relapse of neutropenia occurred in 12 cases within one year. CLINICAL SIGNIFICANCE: Initial response of presumed primary immune-mediated neutropenia cases to corticosteroid therapy can be excellent. Long-term monitoring for relapse is warranted because 34% of cases relapsed during or after taper of immunosuppressive medications.

Serum Beta Hydroxybutyrate Concentrations in Cats with Chronic Kidney Disease, Hyperthyroidism, or Hepatic Lipidosis.

BACKGROUND: Ketones, including beta hydroxybutyrate (BHB), are produced in conditions of negative energy balance and decreased glucose utilization. Serum BHB concentrations in cats are poorly characterized in diseases other than diabetes mellitus. HYPOTHESIS: Serum BHB concentrations will be increased in cats with chronic kidney disease (CKD), hyperthyroidism (HT), or hepatic lipidosis (HL). ANIMALS: Twenty-eight client-owned cats with CKD, 34 cats with HT, and 15 cats with HL; 43 healthy cats. METHODS: Prospective observational study. Serum BHB concentrations were measured at admission in cats with CKD, HT, and HL, for comparison with a reference interval established using healthy cats. Results of dipstick urine ketone measurement, when available, were compared to BHB measurement. RESULTS: Beta hydroxybutyrate was above the reference interval (<0.11 mmol/L) in 6/28 cats (21%) with CKD, 7/34 cats (20%) with HT, and 11/15 cats (73%) with HL, significantly exceeding the expected 2.5% above the reference interval for healthy cats (P < .001 for all groups). Elevations were mild in CKD and HT groups (median BHB 0.1 mmol/L for both groups, 80th percentile 0.12 and 0.11 mmol/L, respectively), but more marked in HL cats (median BHB 0.2 mmol/L, 80th percentile 0.84 mmol/L). None of 11 cats with increased serum BHB concentration having urine dipstick analysis performed within 24 h of sampling for BHB were ketonuric. CONCLUSIONS AND CLINICAL IMPORTANCE: Increases in serum BHB concentrations occur in cats with CKD, HT, and HL, and might provide an useful index of catabolism.

Fasting urinary calcium-to-creatinine and oxalate-to-creatinine ratios in dogs with calcium oxalate urolithiasis and breed-matched controls.

BACKGROUND: Hypercalciuria and hyperoxaluria are risk factors for calcium oxalate (CaOx) urolithiasis, but breed-specific reports of urinary metabolites and their relationship with stone status are lacking. OBJECTIVE: To compare urinary metabolites (calcium and oxalate) and blood ionized calcium (iCa) concentrations between CaOx stone formers and breed-matched stone-free controls for the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds. ANIMALS: Forty-seven Miniature Schnauzers (23 cases and 24 controls), 27 Bichons Frise (14 cases and 13 controls), and 15 Shih Tzus (7 cases and 8 controls). METHODS: Prospective study. Fasting spot urinary calcium-to-creatinine and oxalate-to-creatinine ratios (UCa/Cr and UOx/Cr, respectively) and blood iCa concentrations were measured and compared between cases and controls within and across breeds. Regression models were used to test the effect of patient and environmental factors on these variables. RESULTS: UCa/Cr was higher in cases than controls for each of the 3 breeds. In addition to stone status, being on a therapeutic food designed to prevent CaOx stone recurrence was associated with higher UCa/Cr. UOx/Cr did not differ between cases and controls for any of the breeds. Blood iCa was higher in cases than controls in the Miniature Schnauzer and Bichon Frise breeds and had a moderate correlation with UCa/Cr. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypercalciuria is associated with CaOx stone status in the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds. UOx/Cr did not correlate with stone status in these 3 breeds. These findings may influence breed-specific stone prevention recommendations.

Platelet volume and plateletcrit in dogs with presumed primary immune-mediated thrombocytopenia.

BACKGROUND: Mean platelet volume (MPV) and plateletcrit (PCT) are indices used in evaluating immune-mediated thrombocytopenia (IMT) in humans and in dogs with congenital macrothrombocytopenia. These indices may provide clinically valuable information in acquired thrombocytopenia. HYPOTHESIS/OBJECTIVES: Dogs with presumed primary IMT will have increased MPV, and therefore platelet mass (PCT) will increase faster than platelet count (PLT) during recovery. ANIMALS: Forty-nine dogs with automated PLT < 30,000/µL because of presumed primary IMT and hematocrit (HCT), PCT, MPV, and platelet distribution width determined from the same complete blood count (CBC), and 46 healthy controls. METHODS: Case-control retrospective study; PLT, PCT, MPV, and platelet distribution width (PDW) were recorded from CBCs from 49 dogs, with 45 having data collected on the day of presentation. Fifteen were confirmed to have attained a PLT ≥ 75,000/µL on at least 1 CBC within 15 days after admission. The PCT equivalent to a PLT of 75,000/µL (assuming an average MPV) was calculated for comparison with PLT in terms of time to achieve a threshold of platelet mass by the 2 measures. RESULTS: Mean platelet volume was higher in IMT dogs (17.3 fl) than the reference population (10.5 fl) (P < .0001). The PDW was not significantly different among the groups. The median time for PCT to reach threshold in confirmed responders was faster (3 days) compared with PLT (4 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Immune-mediated thrombocytopenia is characterized by increased MPV. Time to achieve a threshold PCT tended to be shorter than PLT, suggesting that PCT may be a useful platelet parameter for monitoring dogs with IMT.

Clinical features, intestinal histopathology, and outcome in protein-losing enteropathy in Yorkshire Terrier dogs.

BACKGROUND: A poorly understood protein-losing enteropathy (PLE) disorder has been reported in Yorkshire Terrier dogs. OBJECTIVES: To describe clinical features, intestinal histopathology, and outcome in Yorkshire Terrier dogs with PLE, and to identify variables predictive of outcome. ANIMALS: Thirty client-owned Yorkshire Terrier dogs with PLE. METHODS: Retrospective study. Records of dogs with a diagnosis of PLE were reviewed. Intestinal histopathology was interpreted using the World Small Animal Veterinary Association gastrointestinal histopathology classification system. Discriminate analysis techniques were used to identify variables predictive of outcome. RESULTS: Females outnumbered males (20/30). Median age was 7 years (range 1-12). Common clinical signs were diarrhea (20/30), vomiting (11), ascites and abdominal distension (11), and respiratory difficulty (8). Histopathologic abnormalities included villous lymphatic dilatation, crypt lesions, villous stunting, and variable increases in cellularity of the lamina propria. All dogs were treated with glucocorticoids. Of 23 dogs with long-term follow-up, 9 had complete, and 3 had partial, resolution of signs, and 11 failed to respond to treatment. Median survival of responders was 44 months and of nonresponders was 12 months, with 4 dogs experiencing peracute death. Vomiting, monocytosis, severity of hypoalbuminemia, low blood urea nitrogen concentration, and villous blunting were predictive of survival <4 months. CONCLUSIONS: In addition to classic GI signs, Yorkshire Terriers with PLE often show clinical signs associated with hypoalbuminemia and low oncotic pressure. Lymphatic dilatation, crypt lesions, and villous stunting are consistent histopathologic findings. Clinical outcomes are variable, but many dogs experience remission of clinical signs and prolonged survival.

Obesity and sex influence insulin resistance and total and multimer adiponectin levels in adult neutered domestic shorthair client-owned cats.

In this study, we estimated insulin sensitivity and determined plasma concentrations of total-, low-molecular-weight (LMW), and high-molecular-weight (HMW) adiponectin and leptin in 72 domestic shorthair, neutered, client-owned cats. Glucose tolerance was assessed with an intravenous glucose tolerance test and body fat percentage (BF%) was measured with dual-energy x-ray absorptiometry. Total adiponectin was measured with 2 different ELISAs. Low-molecular-weight and HMW adiponectin plasma concentrations were determined by Western blot analysis after sucrose-gradient velocity centrifugation, and the adiponectin multimer ratio [SA = HMW/(HMW + LMW)] was calculated. Differences in glucose tolerance, leptin, total adiponectin, and multimer ratio among lean (BF% <35; n = 26), overweight (35 45; n = 18) cats as well as between male (n = 34) and female (n = 38) neutered cats were evaluated by linear regression and 2-way ANOVA. Sex and age were included as covariates for analysis of BF%, whereas BF%, fat mass, and lean body mass were covariates for analysis of sex differences. Increased BF% was negatively correlated with multimer ratio (SA, r = -45; P < 0.002), whereas no differences were found in total adiponectin concentrations among BF% groups (P > 0.01). Male cats had indices of decreased insulin tolerance and significantly lower total adiponectin concentrations than did female cats (mean ± SEM, 3.7 ± 0.4 vs 5.4 ± 0.5 µg/mL; P < 0.02). Altered SAs could contribute to an obesity-associated decreasing glucose tolerance in cats, and low total adiponectin concentrations may relate to increased risk of diabetes mellitus in neutered male cats.

Amino acid, iodine, selenium, and coat color status among hyperthyroid, Siamese, and age-matched control cats.

BACKGROUND: Hyperthyroidism is common among older cats, but its pathogenesis remains poorly understood. Siamese and Himalayan cats have a reduced risk of hyperthyroidism compared with domestic short-hair cat breeds. A mechanism of risk reduction in pointed-coat breeds is unknown. OBJECTIVES: To determine if tyrosine, phenylalanine, iodine, or selenium blood concentrations are altered in hyperthyroid cats and to describe the plasma amino acid profiles of client-owned cats with naturally occurring hyperthyroidism. ANIMALS: Twenty-seven client-owned cats with (n = 12) and without (n = 15) hyperthyroidism were studied. METHODS: Cross-sectional study. Hyperthyroid cats were prospectively recruited among cats presenting for radioiodine therapy. Control cats were recruited among pets of hospital personnel. Blood was collected for total thyroxine, plasma amino acid, selenium, and iodine determination. Coat color (8 white or pointed; 19 dark), breed, and diet history were recorded. RESULTS: Tyrosine, phenylalanine, iodine, and selenium levels were not significantly different among light or dark cats or cats with or without hyperthyroidism (P > .05). Plasma amino acid profiles of hyperthyroid cats and control cats were similar, and neither group was deficient in any of the amino acids. L-glutamine was significantly lower in cats with hyperthyroidism (mean ± SD: 648 ± 193) compared with control cats (816 ± 134; P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Altered tyrosine, iodine, and selenium metabolism were not associated with coat color or hyperthyroidism in pointed or light coat-colored cats.

High prevalence of the c.74A>C SPINK1 variant in miniature and standard Schnauzers.

BACKGROUND: Variants in the serine protease inhibitor Kazal type 1 (SPINK1) gene have been associated with pancreatitis in Miniature Schnauzers. Replication of the association in an independent population is necessary to determine if genetic screening for SPINK1 variants should be considered in clinical practice. HYPOTHESIS: An association between the SPINK1 exonic variant c.74A > C and pancreatitis exists in Miniature Schnauzers. In addition, the variant is absent or rare in Standard Schnauzers, a related breed that is not reported to have an increased risk for pancreatitis. ANIMALS: Case-control study. Seventeen Miniature Schnauzers with pancreatitis (cases), 60 mature Miniature Schnauzers with no substantial history of gastrointestinal signs in their lifetime (controls), and 31 Standard Schnauzers of unknown pancreatitis status. METHODS: A PCR-RFLP assay was used to genotype dogs for the c.74A > C SPINK1 variant. Allele and genotype frequencies were reported for Schnauzers and compared between case and control Miniature Schnauzers. RESULTS: The c.74A > C variant was the major allele in both Schnauzer breeds with a frequency of 0.77 in Miniatures and 0.55 in Standards. The allele and genotype frequencies were similar between Miniature Schnauzers with and without a history of pancreatitis and did not impart an increased risk for pancreatitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Genotyping a larger population of the Miniature Schnauzer breed than a previous study, along with a Standard Schnauzer cohort, demonstrated that the SPINK1 c.74A > C variant is a common polymorphism in the Schnauzer lineage. Furthermore, we were unable to confirm a relationship between the variant and clinically detectable pancreatitis in Miniature Schnauzers.

Evaluation of microsatellite instability in urine for the diagnosis of transitional cell carcinoma of the lower urinary tract in dogs.

BACKGROUND: The accumulation of frame-shift mutations in microsatellites (MS), termed microsatellite instability (MSI), is associated with certain tumors. MSI and its detection in urine samples has been used to aid in the detection of human bladder cancer. HYPOTHESIS: Evaluation of MSI in urine is a useful assay test for diagnosis of transitional cell carcinoma (TCC) in dogs and is more specific than the commercially available, veterinary bladder tumor analyte (V-BTA) test. ANIMALS: Seventy-three dogs: healthy controls (n=21), proteinuric (n=12), lower urinary tract disease excluding TCC (n=17), and TCC (n=23). METHODS: Prospective observational study. Urine samples collected from each animal were evaluated for MSI and using the V-BTA. For MSI detection, 22 MS sequences were polymerase chain reaction amplified from urine and blood, subjected to capillary electrophoresis, and the MS genotypes were compared. Aberration in ≥15% of MS was considered indicative of MSI. RESULTS: MSI was detected in 11 of 23 (48%) urine samples from dogs with TCC. MSI was also detected in 12 of 50 (24%) of the control animals, including 29, 16, and 24% of healthy, proteinuric, and lower urinary disease dogs, respectively. In this population, sensitivity and specificity of MSI analysis was 48 and 76%, respectively, compared with 83 and 64%, respectively, for the V-BTA test. CONCLUSIONS: MS analysis as performed in this study is not useful in the diagnosis of TCC.

Treatment of immune-mediated hemolytic anemia with individually adjusted heparin dosing in dogs.

BACKGROUND: A major cause of death in dogs with immune-mediated hemolytic anemia (IMHA) is thromboembolism. Previous studies suggest unfractionated heparin (UH) is not effective in preventing thromboembolism in IMHA; however, subtherapeutic dosing could explain the seeming lack of efficacy. HYPOTHESIS: Providing therapeutic plasma concentration of UH by individually adjusting doses based on antifactor Xa activity would improve survival in IMHA. ANIMALS: Fifteen dogs with primary IMHA. METHODS: Randomized, prospective, controlled clinical trial. Dogs received standardized therapy for IMHA and either constant dose (CD) (150 U/kg SC) (n = 7) or individually adjusted dose (IAD) (n = 8) UH, monitored via an anti-Xa chromogenic assay, adjusted according to a nomogram. UH was administered every 6 hours until day 7, and every 8 hours thereafter. UH dose was adjusted daily in IAD dogs until day 7, weekly until day 28, then tapered over 1 week. Dogs were monitored for 180 days. RESULTS: At day 180, 7 dogs in the IAD group and 1 in the CD group were alive (P= .01). Median survival time for the IAD group was >180 days, and 68 days for the CD group. Thromboembolic events occurred in 5 dogs in the CD group and 2 dogs in the IAD group. Doses of UH between 150 and 566 U/kg achieved therapeutic anti-Xa activity (0.35-0.7 U/mL). CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that IAD UH therapy using anti-Xa monitoring reduced case fatality rate in dogs with IMHA when compared with dogs receiving fixed low dose UH therapy.

A prospective, randomized, double-blinded, placebo-controlled study of human intravenous immunoglobulin for the acute management of presumptive primary immune-mediated thrombocytopenia in dogs.

BACKGROUND: Immune-mediated thrombocytopenia (IMT) is a common hematologic disorder in dogs. Human intravenous immunoglobulin (hIVIG) may have a beneficial effect in canine IMT. HYPOTHESIS: A single hIVIG infusion (0.5 g/kg) in dogs with presumed primary IMT (pIMT) is a safe adjunctive emergency treatment to accelerate platelet count recovery and shorten hospitalization time without increasing the cost of patient care. ANIMALS: Eighteen client-owned dogs with a presumptive diagnosis of pIMT. METHODS: Prospective, randomized, double-blinded, placebo-controlled clinical trial. RESULTS: There were no identifiable immediate or delayed adverse reactions associated with hIVIG administration over a 6-month period. The median platelet count recovery time for the hIVIG group was 3.5 days (mean + or - SD: 3.7 + or - 1.3 days; range, 2-7 days) and 7.5 days (mean + or - SD: 7.8 + or - 3.9 days; range, 3-12 days) for the placebo group. The median duration of hospitalization for hIVIG group was 4 days (mean + or - SD: 4.2 + or - 0.4 days; range, 2-8 days) and 8 days (mean + or - SD: 8.3 + or - 0.6 days; range, 4-12 days) for the placebo group. There was no significant difference between groups with respect to expense of initial patient care, whereas significant reduction in platelet count recovery time (P= .018) and duration of hospitalization (P= .027) were detected in the hIVIG group. CONCLUSIONS AND CLINICAL IMPORTANCE: Compared with corticosteroids alone, adjunctive emergency therapy of a single hIVIG infusion was safe and associated with a significant reduction in platelet count recovery time and duration of hospitalization without increasing the expense of medical care in a small group of dogs with presumed pIMT.

Abdominal wall hernia repair: a comparison of Permacol and Surgisis grafts in a rat hernia model.

BACKGROUND: This study compared two porcine-derived grafts Permacol (Tissue Science Laboratory, Covington, GA, USA) and Surgisis (Cook Surgical, Bloomington, IN, USA) in terms of strength of incorporation (SOI), incorporation of host tissue, and adhesion formation using a rat model. METHODS: A prospective randomized study using 48 Sprague-Dawley rats. A standardized 1.5 x 5 cm fascial defect was created and repaired with either Permacol or Surgisis grafts. The rats were then sacrificed at 3, 14, 28, or 60 days. The specimens were examined for SOI, neovascularization, collagen deposition, collagen organization, and adhesion formation. RESULTS: Surgisis had significantly greater SOI than Permacol at 28 (0.115 vs. 0.0754 Mpa) and 60 days (0.131 vs. 0.635 Mpa). Surgisis had significantly more collagen deposition and neovascularization than Permacol at 60 days. The area of adhesions was not significantly different between Surgisis and Permacol. CONCLUSION: Surgisis is superior to Permacol in terms of SOI and tissue ingrowth at 60 days. Furthermore, Surgisis strengthened over time whereas Permacol decreased in strength.

Autosomal dominant canine malignant hyperthermia is caused by a mutation in the gene encoding the skeletal muscle calcium release channel (RYR1).

BACKGROUND: Malignant hyperthermia (MH) is an inherited disorder of skeletal muscle characterized by hypercarbia, rhabdomyolysis, generalized skeletal muscle contracture, cardiac dysrhythmia, and renal failure, that develops on exposure to succinylcholine or volatile anesthetic agents. All swine and up to 50% of human MH events are thought to be associated with mutations in the calcium release channel of the sarcoplasmic reticulum, also known as the ryanodine receptor (RYR1). Events resembling MH have been reported in other species, but none have undergone genetic investigation to date. METHODS: To determine the molecular basis of canine MH, a breeding colony was established with a male, mixed-breed, MH-susceptible (MHS) dog that survived an in vivo halothane-succinylcholine challenge. He was mated to three unaffected females to produce four litters and back-crossed to an affected daughter to produce one litter. One of his MHS sons was mated to an unaffected female to produce an additional litter. Forty-seven dogs were phenotyped with an in vitro contracture test and diagnosed as MHS or MH normal based on the North American in vitro contracture test protocol. Nine microsatellite markers in the vicinity of RYR1 on canine chromosome 1 (CFA01) were tested for linkage to the MHS phenotype. Mutational analysis in two MHS and two MH-normal dogs was performed with direct sequencing of polymerase chain reaction products and of cloned fragments that represent frequently mutated human RYR1 regions. A restriction fragment length polymorphism was chosen to detect the candidate mutation in the pedigree at large. RESULTS: Pedigree inspection revealed that MHS in this colony is transmitted as an autosomal dominant trait. FH2294, the marker closest to RYR1, is linked to MHS at a theta = 0.03 with a LOD score of 9.24. A T1640C mutation gives rise to an alanine for valine substitution of amino acid 547 in the RYR1 protein, generating a maximum LOD score of 12.29 at theta = 0.00. All dogs diagnosed as MHS by in vitro contracture test were heterozygous for the mutation, and all MH-normal dogs were homozygous for the T1640 allele. CONCLUSIONS: These results indicate that autosomal dominant canine MH is caused by a mutation in the gene encoding the skeletal muscle calcium release channel and that the MHS trait in this pedigree of mixed-breed dogs is in perfect cosegregation with the RYR1 V547A mutation.

Elastase is not sufficient to induce experimental abdominal aortic aneurysms.

PURPOSE: Research investigating abdominal aortic aneurysms (AAAs) commonly uses a rat model dependent on aortic infusion of porcine pancreatic elastase to initiate AAA formation. Unfortunately, the sizes of AAAs generated by this model have varied widely among published studies. This may reflect lot-to-lot variations in commercial elastase preparations. This study was undertaken to investigate the ability of different lots of elastase to induce AAAs and explain the variability identified. METHODS: Four lots of elastase were evaluated in the standard rat AAA model. Saline solution was used as a control. Additional groups of rats were treated with higher concentrations of elastase with or without the macrophage activator thioglycollate medium. Aortic diameters were measured in all rats. Inflammation and elastin degradation was examined histologically. Elastase activity and purity were evaluated for all lots. RESULTS: Of the four lots tested, only one was able to consistently generate AAAs at the standard dose (P <.05). Increasing the amount of elastase infused produced AAAs in some ineffective lots. Infusion of thioglycollate medium in combination with otherwise ineffective elastase produced AAAs (P =.02). However, the elastase with the highest purity failed to generate AAAs, even at the highest dose tested or in combination with thyioglycollate medium. Thioglycollate medium alone failed to result in AAA formation. All elastase lots displayed elastolytic activity in vitro and produced elastin degradation in vivo. Elastin degradation did not correlate with AAA size in elastase-treated rats (P = NS). Aneurysm size correlated with extent of inflammation (P =.005). CONCLUSION: Induction of AAAs does not correlate with elastolytic activity. Infusion of pure elastase alone is not sufficient to induce AAA formation in spite of evidence of elastin degradation. Presumed inflammatory modifiers, which contaminate some elastase preparations, enhance AAA formation. Future use of this rat model will need to take the variability of elastase preparations into account with controls for each new elastase lot.

Itraconazole for treatment of sporotrichosis in a dog residing on a Christmas tree farm.

Sporotrichosis was diagnosed in a 2-year-old male Golden Retriever that was allowed to roam free on the owner's Christmas tree farm in Minnesota. Clinical signs had been evident for 1 month and included swelling of the claw bed of the third digit on the left forelimb and a fluctuant nodular lesion in the area of the left carpus. Few organisms were seen in affected tissues, and diagnosis was confirmed on the basis of results of fungal culture. The condition responded to treatment with itraconazole. Previous reports of sporotrichosis in dogs have described lesions that were distributed predominantly on the head, ears, and trunk. A history of exposure to environments that favor survival of the organism may be an important consideration when evaluating animals suspected to have sporotrichosis. To the authors' knowledge, use of itraconazole to treat a dog with sporotrichosis has not been reported previously.

Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States.

OBJECTIVE: To determine age, breed, sex, body condition score, and diet of dogs and cats examined at private veterinary practices in the United States during 1995, and estimate prevalences of the most common disorders for these animals. DESIGN: Cross-sectional study. ANIMALS: 31,484 dogs and 15,226 cats examined by veterinary practitioners at 52 private veterinary practices. PROCEDURE: Information on age, breed, sex, body condition score, diet, and assigned diagnostic codes were collected electronically from participating practices and transferred to a relational database. Prevalence estimates and frequencies for population description were generated using statistical software. RESULTS: Dental calculus and gingivitis were the most commonly reported disorders. About 7% of dogs and 10% of cats examined by practitioners during the study were considered healthy. Many conditions were common to both species (e.g., flea infestation, conjunctivitis, diarrhea, vomiting). Dogs were likely to be examined because of lameness, disk disease, lipoma, and allergic dermatitis. Cats were likely to be examined because of renal disease, cystitis, feline urologic syndrome, and inappetence. CLINICAL IMPLICATIONS: Results can be used by veterinary practitioners to better understand and anticipate health problems of importance in cats and dogs they examine and to better communicate with clients regarding the most prevalent disorders in cats and dogs.

Bee sting envenomation resulting in secondary immune-mediated hemolytic anemia in two dogs.

Immune-mediated hemolytic anemia secondary to bee envenomation developed in 2 dogs. Clinical signs included lethargy, hematuria, ataxia, and seizures; 1 dog died. Clinicopathologic data included nonregenerative anemia, spherocytosis, positive results for Coombs' test, and occult hematuria. Treatment included oral administration of corticosteroids at immunosuppressive dosages and supportive care. The surviving dog initially responded to corticosteroids, but hemolysis recurred as the dosage was tapered. Hemolysis resolved with prolonged administration of corticosteroids. Bee venom contains hyaluronidase, histamines, and hemolysins that cause toxic and hemolytic effects. Envenomation should be considered in any dog with hemolytic anemia in which other causes are ruled out and exposure to bees is known.

Clinical features of inflammatory liver disease in cats: 41 cases (1983-1993).

OBJECTIVE: To compare the clinical and clinicopathologic findings in and prognosis for cats with lymphocytic portal hepatitis (LPH) versus cats with acute or chronic cholangiohepatitis (CH). DESIGN: Retrospective study. ANIMALS: 25 cats with LPH; 16 cats with CH (7 acute, 9 chronic). PROCEDURE: Cats with LPH and CH were selected by evaluating records from liver biopsy specimens submitted to the University of Minnesota Veterinary Teaching Hospital during a 10-year period. Clinical and clinicopathologic data were retrieved. RESULTS: Cats with CH had higher segmented and band neutrophil counts, alanine aminotransferase activities, and total bilirubin concentrations than did cats with LPH. Cats with acute CH had higher segmented and band neutrophil counts and lower serum alkaline phosphatase activities and total bilirubin concentrations than did cats with chronic CH. Twelve of 14 cats with LPH or CH had coarse or nodular texture to the liver on ultrasonography, with loss of portal vein wall clarity noticed in 4 of 8 cats with LPH. Sixteen of 23 cats with LPH and 8 of 15 cats with CH survived > 1 year. Of those cats living < 1 year, all cats with LPH and 5 of 7 cats with CH had a serious concurrent illness that may have been responsible for their deaths. CLINICAL IMPLICATIONS: LPH and CH can be detected and tentatively differentiated through evaluation of clinical laboratory test results, but histologic evaluation of liver specimens is necessary for definitive differentiation. Survival time was good regardless of the type of inflammatory liver disease.