bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Platelet Aggregation Using a Point‐Of‐Care Instrument in Retired Racing Greyhounds
Authors: Couto C.G. , Lara A. , Iazbik M.C. , Brooks M.B.
Published: March 2010

Veterinarians involved in Greyhound rescue have anecdotally observed that 10–15% of Greyhounds bleed profusely after simple surgical procedures. In most patients, platelet counts and hemostasis profiles are normal; therefore, it is possible that these dogs have platelet dysfunction. The PFA‐100ais a novel point‐of‐care platelet function analyzer that has recently been evaluated as a rapid method to assess platelet function in dogs. The objectives of this study were to characterize platelet function in a group of healthy Greyhounds by means of the PFA‐100. Blood samples were collected from the jugular vein from 30 healthy Greyhounds. CBC, biochemical profile, PFA‐100 assay with collagen/epinephrine (COL‐EPI) and collagen/ adenosindiphosphate (COL‐ADP), plasma von Willebrand factor antigen concentration (vWF: Ag), and vWF collagen‐binding assay (vWF:CBA) were performed. PFA‐100 closure times (CTs) with COL/ADP ranged from 63 to 92 seconds (mean ± SD, 74.7 ± 7.9 seconds) and with COL/EPI from 87 to 238 seconds (138 ± 41 seconds); vWF:Ag ranged from 22 to 120% (87.52 ± 25.5%) and vWF:CBA ranged from 36 to 102% (77.4 ± 17.3%); and platelet counts ranged from 147 to 265 ± 109/L (194.6 ± 31.64 ± 109/L). Greyhound CTs were significantly shorter than CTs in a mixed population of 50 healthy non‐Greyhound dogs, in which the COL/ADP CTs ranged from 61 to 172 seconds (mean ± SD, 87 ± 21.6 seconds), and the COL/ EPI CTs ranged from 81 to 300 seconds (mean ± SD, 183 ± 67.6 seconds;P= 0.005 for COL/ADP CT;P= 0.001 for COL/ EPI CT). Also, platelet counts were significantly lower (P= 0.001) and packed cell volume was significantly higher (P= 0.001) in the Greyhound than in the non‐Greyhound group. The PFA‐100 is a reproducible method that can be used in the clinical setting to assess platelet function in Greyhounds; however, normal CTs in healthy Greyhounds are shorter than in other breeds. The results obtained in this study will be used to screen for abnormal platelet function in Greyhounds with postoperative bleeding.
Efficacy of Ronidazole for Treatment of FelineTritrichomonas foetusInfection
Authors: Gookin Jody L. , Copple Christina N. , Papich Mark G. , Poore Matthew F. , Stauffer Stephen H. , Birkenheuer Adam J. , Twedt David C. , Levy Michael G.
Published: March 2010

Objectives: To determine the efficacy of ronidazole (RDZ), tinidazole (TDZ), and metronidazole (MDZ) againstTritrichomonas foetusin vitro and of RDZ for treatment of feline naturally occurring or experimentally inducedT foetusinfection.

Animals: A cat naturally infected withT foetusinfection and diarrhea. Ten specific‐pathogen‐free (SPF) kittens.

Procedure: RDZ, TDZ, and MDZ were tested for activity against 3 different feline isolates ofT foetusin vitro. RDZ then was administered to a naturally infected cat at 10 mg/kg PO q24h for 10 days. SPF kittens were infected orogastrically with felineT foetusand treated with either placebo or RDZ (10 mg/kg PO q12h for 14 days). Cats with relapsing infection or those receiving placebo were treated subsequently with RDZ (either 30 or 50 mg/kg PO q12h for 14 days). Feces were examined forT foetusby direct microscopy, culture, and polymerase chain reaction (PCR) testing weekly.

Results: Both RDZ and TDZ killedT foetusat concentrations >0.1 μg/mL in vitro. In the naturally infected cat, RDZ abolished diarrhea andT foetusinfection for 85 days after treatment, at which time infection and diarrhea relapsed. Retreatment with RDZ eradicated diarrhea andT foetusinfection for over 407 days. In experimentally induced infection, RDZ at 10 mg/kg caused initial improvement, but infection relapsed in all 5 cats 2 to 20 weeks after treatment. At 30 or 50 mg/kg, 10/10 cats were negative forT foetusinfection for follow‐up durations of 21 to 30 weeks after treatment.

Conclusions and Clinical Relevance: Oral administration of RDZ at 30 to 50 mg/kg q12h for 14 days resolved diarrhea and eradicated infection (on the basis of polymerase chain reaction [PCR] testing) in 1 naturally infected cat and 10 experimentally inoculated cats receiving a different isolate ofT foetus.
Effects of Fenoldopam Mesylate on Systemic Hemodynamics and Indices of Renal Function in Normotensive Neonatal Foals
Authors: Hollis Anna R. , Ouseyxya Jennifer C. , Palmer Lorraine , Stoneham Sarah J. , Corley Kevin T.T.
Published: March 2010

Background: Fenoldopam mesylate, a dopamine‐1 receptor agonist, has dose‐ and species‐dependent effects on hemodynamics and renal function. The effects of this drug in normotensive neonatal foals have not been reported.

Hypothesis: Two doses of fenoldopam would result in distinct changes in the systemic circulation, urine output, and creatinine clearance of neonatal foals.

Animals: Six Thoroughbred foals.

Methods: Each foal received 2 dosages of fenoldopam (low dose, 0.04 μg/kg/min; high dose, 0.4 μg/kg/min) and a control administration of saline, in a masked, placebo‐controlled study.

Results: High‐dosage fenoldopam had no effect on renal function but caused a significant increase in heart rate and decrease in mean, systolic and diastolic arterial blood pressure compared with saline. Low‐dosage fenoldopam had no effects on systemic hemodynamics, significantly increased urine output, and had no significant effect on creatinine clearance or the fractional excretions of sodium, potassium, or chloride compared with saline.

Conclusions and Clinical Importance: These data suggest that high‐dosage fenoldopam increases heart rate, decreases arterial blood pressure, and has no significant effects on renal function, whereas low‐dosage fenoldopam has no significant effects on systemic hemodynamics while increasing urine output. This contrast is unique to this species and warrants further investigation.
Detection of Activated Platelets in Dogs with Primary Immune‐Mediated Hemolytic Anemia
Authors: Weiss Douglas J. , Brazzell Jennifer L.
Published: March 2010

Thromboembolism is a major cause of morbidity and mortality in dogs with immune‐mediated hemolytic anemia (IMHA). To the authors' knowledge, the role of platelets in thromboembolic events associated with IMHA has not been extensively investigated. In the study reported here, we evaluated cell membrane expression of P‐selectin with flow cytometry to determine whether platelets circulate in an activated state in association with primary IMHA. Median P‐selectin expression for 20 dogs with primary IMHA was 8.1‐fold greater, compared with values for 20 healthy dogs. Fifteen of 20 dogs (75%) with IMHA had P‐selectin median fluorescence intensity (MFI) values that exceeded the reference interval for healthy dogs. Additionally, P‐selectin MFI after activation of platelets with phorbol myristate acetate was 2.1‐fold greater for dogs with IMHA than for healthy control dogs. Despite treatment of all dogs with immunosuppressive therapy and 18 dogs with subcutaneously administered low‐dose unfractionated heparin, 7 dogs developed clinical signs consistent with thromboembolism. These data provide support for the hypothesis that platelets circulate in an activated state in many dogs with IMHA.
Triple Antimicrobial Therapy and Acid Suppression in Dogs with Chronic Vomiting and GastricHelicobacterspp
Authors: Leib Michael S. , Duncan Robert B. , Ward Daniel L.
Published: March 2010

Background:Helicobacter pyloriis a common cause of gastritis and peptic ulcers in humans. Many dogs, including those with gastritis and chronic vomiting, are infected withHelicobacterspp.

Hypothesis: Triple antimicrobial therapy will eradicateHelicobacterinfection, improve gastritis, and reduce clinical signs. The addition of acid suppression medication will not improve results.

Animals: Twenty‐four pet dogs with chronic vomiting and gastricHelicobacterspp.

Methods: Dogs were randomly assigned to triple antimicrobial therapy with or without famotidine. Gastroduodenoscopy was performed 4 weeks and 6 months after therapy.Helicobacterspp status was determined by histologic assessment of gastric mucosal biopsy specimens.

Results: Eradication rates for each treatment were not significantly different and combined were 75 and 42.9% at 4 weeks and 6 months, respectively. A greater improvement in gastritis scores occurred in dogs that becameHelicobacterspp negative. Overall, the frequency of vomiting was reduced by 86.4%, but there were no differences between treatments.

Conclusions and Clinical Importance: Eradication rates ofHelicobacterspp with both treatments were not significantly different. Eradication rates at 6 months were modest, and more effective treatments should be developed. Acid suppression is not a necessary component of treatment protocols for dogs. Eradication of gastricHelicobacterspp was associated with improvement in gastritis scores. Dramatic reduction of the vomiting frequency occurred with both treatment protocols. GastricHelicobacterspp may cause or contribute to chronic vomiting and gastritis in some dogs.
Diabetes Mellitus in a Population of 180,000 Insured Dogs: Incidence, Survival, and Breed Distribution
Authors: Fall Tove , Hamlin Helene Hansson , Hedhammar Åke , Kämpe Olle , Egenvall Agneta
Published: March 2010

Background: Canine diabetes mellitus (DM) is a common endocrinopathy with an unclear etiology. For a better understanding of the underlying mechanisms, there is a need for comprehensive epidemiologic studies. Earlier studies have shown that the risk of disease is higher in certain dog breeds.

Hypothesis: Incidence, age of onset, survival and sex proportion of DM vary by breed.

Animals: Data from a cohort of 182,087 insured dogs aged 5–12 years accounting for 652,898 dog‐years at risk were studied retrospectively.

Methods: Incidence rates by sex, breed, and geography were calculated with exact denominators. Age‐specific incidence and survival after 1st DM claim were computed with Cox's regression and Kaplan‐Meier survival function. Multivariable survival analysis was performed for the outcome diagnosis of DM with age, sex, and geography tested as fixed effects, previous endocrine or pancreatic diseases tested as time‐dependent covariates, and breed tested as a random effect.

Results: The mean age at 1st insurance claim for the 860 DM dogs (72% females) was 8.6 years. The incidence of DM was 13 cases per 10,000 dog‐years at risk. Australian Terriers, Samoyeds, Swedish Elkhounds, and Swedish Lapphunds were found to have the highest incidence. The proportion of females with DM varied significantly among breeds. Swedish Elkhounds, Beagles, Norwegian Elkhounds, and Border Collies that developed DM were almost exclusively females. The multivariable model showed that breed, previous hyperadrenocorticism, and female sex were risk factors for developing DM. Median survival time was 57 days after 1 st claim. Excluding the 223 dogs that died within 1 day, the median survival time was 2 years after 1st claim of DM.

Conclusion: The significant breed‐specific sex and age differences shown in this study indicate that genetic variation could make breeds more or less susceptible to different types of DM.
A Neurologic Syndrome in Golden Retrievers Presenting as a Sensory Ataxic Neuropathy
Authors: Jäderlund K. Hultin , Örvind E. , Johnsson E. , Matiasek K. , Hahn C.N. , Malm S. , Hedhammar Å.
Published: March 2010

Background: A sensory ataxic neuropathy has been observed in Swedish Golden Retrievers recently.

Animals: Twenty‐one affected Golden Retrievers.

Methods: Clinical and neurologic status, electrophysiologic, and pathologic status as well as pedigree analyses were evaluated.

Results: Clinical signs had an insidious onset between 2 and 8 months of age and a slowly progressive course. Affected dogs were ataxic and dysmetric. They had abnormal postural reactions and decreased spinal reflexes but no apparent muscle atrophy. Clinical pathology, radiography, and electrophysiology of motor systems were all within reference values. Sensory nerve conduction results of affected dogs were significantly different from those of a group of control dogs. Necropsy revealed a chronic progressive central and peripheral sensorimotor axonopathy; the proprioceptive pathways were most severely affected.

Conclusions and Clinical Importance: This disease in these Golden Retrievers is distinct from other canine breed‐related neurodegenerative diseases or hereditary neurodegenerative diseases described in humans. Pedigree analyses indicated a hereditary background, but the mode of inheritance could not be established.
Procarbazine as Adjunctive Therapy for Treatment of Dogs with Presumptive Antemortem Diagnosis of Granulomatous Meningoencephalomyelitis: 21 Cases (1998–2004)
Authors: Coates Joan R. , Barone Georgina , Dewey Curtis W. , Vitale Christina L. , Holloway‐Azene Nicole M. , Sessions John K.
Published: March 2010

Background: Granulomatous meningoencephalomyelitis (GME) is an idiopathic inflammatory disease of the central nervous system. Remission often is short‐lived in dogs treated with glucocorticoids. Procarbazine is T cell‐specific and crosses the blood‐brain barrier.

Hypothesis: Dogs with presumptive antemortem diagnosis of GME given procarbazine as adjunctive therapy to prednisone will have improved long‐term outcome compared with dogs given no treatment or glucocorticoids alone.

Animals: Two groups were studied: (1) Dogs with presumptive antemortem diagnosis of GME treated with procarbazine and prednisone (n = 21); (2) Dogs that had a histologic diagnosis of GME at postmortem examination and received no treatment (n = 11).

Methods: Dogs with presumptive GME treated with procarbazine were identified retrospectively from medical records of 2 veterinary referral hospitals. Selection criteria required all dogs have a neurologic examination, blood work, cerebrospinal fluid analysis, and brain imaging (MRI or CT).

Results: Median survival time for all dogs studied was 5.0 months. Median survival time for dogs treated with procarbazine was 14.0 months and for untreated dogs, 0.73 months. Treatment with procarbazine was significantly correlated with survival time (P< .001). Procarbazine was the only independent predictor of survival. Prednisone was reduced in dosage or discontinued in 17 dogs. Adverse reactions to procarbazine therapy included myelosuppression in 7 dogs and hemorrhagic gastroenteritis in 3 dogs.

Conclusion: These data suggest that procarbazine treatment of presumptive GME may result in greater improved long‐term outcome than has been previously reported for glucocorticoid treatment alone and may complement other immunomodulatory therapies. Procarbazine‐treated dogs must be monitored for adverse reactions.
Combination Chemotherapy with L‐Asparaginase, Lomustine, and Prednisone for Relapsed or Refractory Canine Lymphoma
Authors: Saba Corey F. , Thamm Douglas H. , Vail David M.
Published: March 2010

Background: Canine lymphoma (LSA) is responsive to initial treatment, however, it then becomes resistant to drugs in the initial protocol. New rescue protocols are needed.

Hypothesis: A combination of L‐asparaginase, lomustine, and prednisone will be well tolerated and efficacious as a rescue therapy for dogs with LSA.

Animals: Thirty‐one client owned dogs with cytologically confirmed multicentric LSA who were refractory or whose disease had relapsed after a CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)‐based chemotherapy protocol.

Methods: Prospective clinical trial. Lomustine (target dose, 70 mg/m2) was administered orally at 3‐week intervals for a total of 5 doses or until disease progression. L‐asparaginase (400 U/kg) was administered subcutaneously concurrently with the first 2 lomustine treatments. Prednisone was administered at a tapering dose for the duration of the protocol.

Results: Overall response rate for dogs treated with this protocol was 87% (27/31), with 52% (16/31) of dogs achieving a complete response. Median time to response was 21 days. Median time to progression was 63 days (111 days for dogs achieving a complete response and 42 days for dogs achieving a partial response). There were no significant differences in response rates and times to progression between dogs who had received L‐asparaginase before beginning this rescue protocol and those who had not. Toxicoses were mild and self‐limiting in 29 of 31 cases.

Conclusions and Clinical Importance: This is a well‐tolerated rescue therapy for relapsing LSA in dogs. Response rates and remission durations compare favorably to other rescue protocols. Therefore, this protocol is a viable rescue option.
Expression of Receptor Activator of Nuclear Factor k‐B Ligand (RANKL) in Neoplasms of Dogs and Cats
Authors: Barger Anne M. , Fan Timothy M. , de Lorimier Louis‐Philippe , Sprandel Ian T. , O'Dell‐Anderson Kristen
Published: March 2010

Background: Receptor activator of nuclear factor K‐B (RANK), RANK‐ligand (RANKL), and the soluble decoy receptor osteoprotegerin (OPG) form a key axis modulating osteoclastogenesis. In health, RANKL‐expressing bone stromal cells and osteoblasts activate osteoclasts through RANK ligation, resulting in homeostatic bone resorption. Skeletal tumors of dogs and cats, whether primary or metastatic, may express RANKL and directly induce malignant osteolysis.

Hypothesis: Bone malignancies of dogs and cats may express RANKL, thereby contributing to pathologic bone resorption and pain. Furthermore, relative RANKL expression in bone tumors may correlate with radiographic characteristics of bone pathology.

Animals: Forty‐two dogs and 6 cats with spontaneously‐occurring tumors involving bones or soft tissues were evaluated.

Methods: A polyclonal anti‐human RANKL antibody was validated for use in canine and feline cells by flow cytometry and immunocytochemistry. Fifty cytologic specimens were collected from bone and soft tissue tumors of 48 tumor‐bearing animals and assessed for RANKL expression. In 15 canine osteosarcoma (OSA) samples, relative RANKL expression was correlated with radiographic characteristics of bone pathology.

Results: Expression of RANKL by neoplastic cells was identified in 32/44 canine and 5/6 feline tumor samples. In 15 dogs with OSA, relative RANKL expression did not correlate with either radiographic osteolysis or bone mineral density as assessed by dual energy x‐ray absorptiometry.

Conclusions and Clinical Importance: In dogs and cats, tumors classically involving bone and causing pain, often may express RANKL. Confirming RANKL expression in tumors is a necessary step toward the rational institution of novel therapies targeting malignant osteolysis via RANKL antagonism.
Tissue Doppler Imaging in Maine Coon Cats with a Mutation of Myosin Binding Protein C with or without Hypertrophy
Authors: MacDonald Kristin A. , Kittleson Mark D. , Kass Philip H. , Meurs Kathryn M.
Published: March 2010

Background: The cardiac myosin binding protein C gene is mutated in Maine Coon (MC) cats with familial hypertrophic cardiomyopathy.

Hypotheses: Early diastolic mitral annular velocity is incrementally reduced from normal cats to MC cats with only an abnormal genotype to MC cats with abnormal genotype and hypertrophy.

Animals:Group 1 consisted of 6 normal domestic shorthair cats, group 2 of 6 MC cats with abnormal genotype but no hypertrophy, and group 3 of 15 MC cats with hypertrophy and abnormal genotype.

Methods:The genotype and echocardiographic phenotype of cats were determined, and the cats were divided into the 3 groups. Tissue Doppler imaging (TDI) of the lateral mitral annulus from the left apical 4‐chamber view was performed. Five nonconsecutive measurements of early diastolic mitral annular velocity (EM) or summated early and late diastolic velocity (EAsum) and heart rate were averaged.

Results:There was an ordered reduction in Em‐EAsum as group number increased (group 1, range 9.7–14.7 cm/s; group 2, range 7.5–13.2 cm/s; group 3, range 4.5–14.1 cm/s;P= .001). Using the lower prediction limit for normal Em‐EAsum, the proportion of cats with normal Em‐EAsum decreased as the group number increased (P= .001). However, Em‐EAsum was reduced in only 3 of 6 cats in group 2.

Conclusion: The incremental reduction of Em‐EAsum as group severity increased indicates that diastolic dysfunction is an early abnormality that occurs before hypertrophy development. TDI measurement of Em or EAsum of the lateral mitral annulus is an insensitive screening test for identification of phenotypically normal, genotypically affected cats.
Synthetic Adrenocorticotropic Hormone Stimulation Tests in Healthy Neonatal Foals
Authors: Hart Kelsey A. , Ferguson Duncan C. , Heusner Gary L. , Barton Michelle Henry
Published: March 2010

Background:Cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation tests are used to evaluate adrenal function. Low‐dose ACTH stimulation tests are the most accurate method for diagnosing relative adrenal insufficiency in critically ill humans but have not been evaluated in foals.

Hypothesis:Peak serum cortisol concentrations in healthy foals will not be significantly different after intravenous administration of 1, 10, 100, and 250 μg of cosyntropin.

Animals:14 healthy neonatal foals, 3–4 days of age.

Methods:A randomized cross‐over model was used in which cosyntropin (1, 10, 100, or 250 μg) was administered intravenously on days 3 and 4 of life. Blood samples were collected before and 30, 60, 90, 120, and 150 minutes after administration of cosyntropin for determination of serum cortisol concentration.

Results:Serum cortisol concentrations did not significantly increase after administration of 1 μg of cosyntropin. Cortisol concentration peaked 30 minutes after administration of 10 μg of cosyntropin and 90 minutes after 100 and 250 μg of cosyntropin. There was no relationship between cosyntropin dose and serum cortisol concentration at 30 minutes. Compared with the 10‐μg dose, 100 and 250 μg of cosyntropin induced significantly greater cortisol concentrations at 90 minutes, at which point the 10‐μg cosyntropin‐dose cortisol values were indistinguishable from baseline. There was no significant difference in the area under the cortisol concentration curve between the 100‐and 250‐μg doses. No effect of day of testing or foal weight on peak cortisol concentration was detected.

Conclusions and Clinical Importance: The results of this study suggest that 10‐and 100‐μg doses of cosyntropin would be appropriate for evaluating adrenal function in neonatal foals.
Day‐to‐Day Variation of the Urine Protein: Creatinine Ratio in Female Dogs with Stable Glomerular Proteinuria Caused by X‐Linked Hereditary Nephropathy
Authors: Nabity Mary B. , Boggess May M. , Kashtan Clifford E. , Lees George E.
Published: March 2010

Background:Interpretation of serial urine protein: creatinine (UPC) values is confounded by a lack of data regarding random biologic variation of UPC values in dogs with stable glomerular proteinuria.

Hypothesis:That there is minimal day‐to‐day variability in the UPC of dogs with unchanging proteinuria and the number of measurements needed to reliably estimate UPC varies with the magnitude of proteinuria.

Animals:Forty‐eight heterozygous (carrier) female dogs with X‐linked hereditary nephropathy (XLHN) causing stable proteinuria.

Methods:Urine samples were obtained daily by cystocentesis for 3 consecutive days on 183 occasions (549 samples). The UPC was measured for each sample with a single dry‐film chemistry auto‐analyzer. Data were analyzed retrospectively by a power of the mean model because the variance of UPC values within the 3‐day evaluation periods increased as the magnitude of proteinuria increased.

Results:To demonstrate a significant difference (P< .05) between serial values in these proteinuric dogs, the UPC must change by at least 35% at high UPC values (near 12) and 80% at low UPC values (near 0.5). One measurement is adequate to reliably estimate the UPC when UPC < 4, but 2–5 determinations are necessary at higher UPC values.

Conclusions and Clinical Importance: These guidelines for interpretation of serial UPC values in female dogs with XLHN may also be helpful for interpretation of UPC values in dogs with other glomerulopathies.
Thyroid Imaging in the Dog: Current Status and Future Directions
Authors: Taeymans O. , Peremans K. , Saunders J.H.
Published: March 2010

This review describes the advantages and disadvantages of radiography, ultrasonography, and nuclear medicine in the 2 most frequent thyroid pathologies of the dog: acquired primary hypothyroidism and thyroid neoplasia. Ultrasonography and scintigraphy remain the 2 most indicated imaging modalities for these thyroid abnormalities. However, as in human medicine, computed tomography and magnetic resonance imaging also have potential indications. This is especially the case in the evaluation of the extent, local invasiveness, and local or distant metastases of thyroid neoplasia. Based on experience with different imaging modalities in people, we suggest future directions in the imaging of the canine thyroid gland.
Doxorubicin and BAY 12–9566 for the Treatment of Osteosarcoma in Dogs: A Randomized, Double‐Blind, Placebo‐Controlled Study
Authors: Moore Antony S. , Dernell William S. , Ogilvie Gregory K. , Kristal Orna , Elmslie Robyn , Kitchell Barbara , Susaneck Steven , Rosenthal Robert , Klein Mary K. , Obradovoich Joyce , Legendre Alfred , Haddad Tara , Hahn Kevin , Powers Barbara E. , Warren Darren
Published: March 2010

Background: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy.

Hypothesis: Survival will be prolonged in dogs receiving BAY 12–9566.

Animals: The study included 303 dogs with appendicular osteosarcoma.

Methods: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12–9566; 4‐[4–4‐(chlorophenyl)phenyl]‐4‐oxo‐2S‐(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy.

Results: Median survival for all 303 dogs was 8 months; and 1‐year, 2‐year, and 3‐year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12–9566 did not influence survival. Multivariate analysis revealed that increasing age (P= .004), increasing weight (P= .006), high serum alkaline phosphatase (ALP) (P= .012) and high bone ALP (P< .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P= .013), and as plasma active MMP‐2 concentrations increased (P= .027), the risk of dying increased.

Conclusions and Clinical Importance: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.
Acute Effects of Carprofen and Meloxicam on Canine Gastrointestinal Permeability and Mucosal Absorptive Capacity
Authors: Craven Melanie , Chandler Marge L. , Steiner Jörg M. , Farhadi Ashkan , Welsh Elizabeth , Pratschke Kathryn , Shaw Darren J. , Williams David A.
Published: March 2010

Background: Nonsteroidal anti‐inflammatory drugs (NSAIDs) are frequently prescribed to dogs for their analgesic, antipyretic, and anti‐inflammatory properties. Their beneficial actions can be offset by gastrointestinal (GI) toxicosis. Endoscopy has traditionally been employed to detect GI lesions, but alterations in GI permeability precede the development of mucosal damage.

Hypothesis: Carprofen and meloxicam alter GI permeability and mucosal absorptive capacity of dogs.

Animals: Twenty adult dogs treated with an NSAID for >.7 days were evaluated by permeability tests while receiving either carprofen (10 dogs) or meloxicam (10 dogs).

Methods: Prospective, longitudinal observational study. A 6‐sugar permeability test (sucrose, lactulose, rhamnose, 3‐O‐methyl‐D‐glucose, D‐xylose, and sucralose) was performed on the day before NSAID treatment, and after 3 and 8 days of treatment.

Results: There were no significant differences in the urinary recovery ratios of lactulose: rhamnose, D‐xylose:3‐O‐methyl‐D‐glucose, or sucralose recovery within either group at any time during the study. Sucrose permeability in the meloxicam group did not alter significantly over time. However, sucrose permeability in the carprofen group decreased significantly by day 3 (P= .049) and increased again by day 8 (P= .049), to a level that was not significantly different to permeability before treatment (P= .695).

Conclusions and Clinical Importance: The absence of increased GI permeability and diminished mucosal absorptive capacity in this group of dogs does not support the development of acute GI toxicosis during treatment with either meloxicam or carprofen.
Hereditary Factor VII Deficiency in the Alaskan Klee Kai Dog
Authors: Kaae Jennifer A. , Callan Mary Beth , Brooks Marjory B.
Published: March 2010

Background: Hereditary factor VII (FVII) deficiency is characterized as a mild bleeding disorder in Beagles, caused by a missense mutation in exon 5 of the FVII gene. An Alaskan Klee Kai dog with severe bleeding after trauma was diagnosed with FVII deficiency based on coagulation testing. Molecular analyses were undertaken to identify the genetic basis of the defect in this breed.

Hypothesis: FVII deficiency in Alaskan Klee Kai dogs is caused by a mutation in the FVII gene.

Animals: Eighteen client‐owned Alaskan Klee Kai.

Methods: Coagulation screening tests and factor assays were performed to characterize the coagulopathy. All coding regions of the propositus' FVII gene were sequenced. Amplification of exon 5, sequencing, andMnlI restriction digest experiments were performed to screen for a point mutation in the remaining 17 dogs.

Results: FVII deficiency was diagnosed in 6 dogs with a median FVII activity (FVII:C) of 5% (reference range, 50–150%). All FVII‐deficient Alaskan Klee Kai were homozygous for the same mutation as FVII‐deficient Beagles (ie, a G to A transition), resulting in substitution of glycine 96 by glutamic acid. An overlap in the FVII: C values obtained from heterozygote and wild‐type dogs precluded accurate detection of carriers without genetic screening.

Conclusions and Clinical Importance: FVII deficiency may be associated with a bleeding tendency and should be considered in Alaskan Klee Kai dogs with prolonged prothrombin times. Plasma FVII:C accurately identifies affected dogs, but deoxyribonucleic acid testing is required for identification of carriers.
Survival, Neurologic Response, and Prognostic Factors in Dogs with Pituitary Masses Treated with Radiation Therapy and Untreated Dogs
Authors: Kent Michael S. , Bommarito David , Feldman Edward , Theon Alain P.
Published: March 2010

Background: Pituitary masses in dogs are not uncommon tumors that can cause endocrine and neurologic signs and, if left untreated, can decrease life expectancy.

Hypothesis: Dogs with pituitary masses that received radiation therapy (RT) have more favorable neurologic outcomes and longer survival times compared with untreated dogs.

Animals: Nineteen dogs with a pituitary mass identified on CT or MR imaging were irradiated with 48 Gy given in 3 Gy daily‐dose fractions. Twenty‐seven untreated control dogs had pituitary masses.

Methods: Medical records of dogs with pituitary masses were retrospectively reviewed for clinical signs, mass size, and outcome.

Results: Median survival time was not reached in the treated group. Mean survival time in the treated group was 1,405 days (95% confidence interval [CI], 1,053–1,757 days) with 1‐, 2‐, and 3‐year estimated survival of 93, 87, and 55%, respectively. Median survival in the nonirradiated group was 359 days (95% CI, 48–916 days), with a mean of 551 days (95% CI, 271–829 days). The 1‐, 2‐, and 3‐year estimated survival was 45, 32, and 25%, respectively. Dogs that received RT for their pituitary tumors had significantly longer survival times than untreated dogs (P =.0039). Treated dogs with smaller tumors (based on maximal pituitary‐to‐brain height ratio or area of tumor to area of brain) lived longer than those with larger tumors (P <.001).

Conclusions and Clinical Importance: When compared with untreated dogs, RT increased survival and controlled neurologic signs in dogs with pituitary masses.
Effect of Fentanyl on Visceral and Somatic Nociception in Conscious Horses
Authors: Sanchez L. Chris , Robertson Sheilah A. , Maxwell Lara K. , Zientek Keith , Cole Cynthia
Published: March 2010

Background: Transdermal fentanyl is used clinically in horses based on pharmacokinetic data and antinociceptive effects documented in other species.

Hypothesis: Fentanyl IV administration increases both visceral and somatic nociceptive threshold in conscious horses.

Animals: Six clinically normal horses, each fitted with a permanent gastric cannula.

Methods: Visceral nociception was evaluated with 2 methods of threshold detection—colorectal distention and duodenal distention. Somatic nociception was assessed by measurement of thermal threshold. Fentanyl was administered as an increasing stepwise infusion followed by a continuous‐rate infusion for a total of 2 hours. There were 4 doses of fentanyl and 1 dose each of saline and xylazine administered to each horse. Serum fentanyl concentrations were measured and the resulting data were used to determine pharmacokinetic parameters for each horse. All data were analyzed by means of a 3‐factor analysis of variance followed by either a simple t test or a Bonferroni t test for multiple comparisons.

Results: Fentanyl administration did not result in significant changes in duodenal or colorectal distention threshold. Thermal threshold showed an increased trend at the 15‐minute time point for the highest fentanyl group only, with a corresponding mean serum fentanyl concentration of 7.82 ± 2.10 ng/mL. Two horses in this group became agitated and tachycardic during the first 15 minutes of the infusion.

Conclusions and Clinical Importance: Fentanyl did not produce a significant antinociceptive effect at the doses used, 2 of which resulted in serum concentrations above the nociceptive threshold in other species.
Assessment of a Point‐of‐Care Lactate Monitor in Emergency Admissions of Adult Horses to a Referral Hospital
Authors: Tennent‐Brown Brett S. , Wilkins Pamela A. , Lindborg Sue , Russell Gail , Boston Raymond C.
Published: March 2010

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.
An Approximation Approach to General Robustness Assessment for Multidisciplinary Systems
Authors: Du Xiaoping , Zhang Yi
Published: March 2010

In many engineering applications, both random and interval variables exist. The mixture of both types of variables has been dealt with in robust design for single-disciplinary systems. This work focuses on robustness assessment for multidisciplinary systems with both random and interval variables. To alleviate the intensive computational demand, a semi-second-order Taylor expansion method is proposed to evaluate robustness. A performance function is approximated with linear terms of random and interval variables, as well as the interaction terms between the two types of variables. Then the maximum and minimum standard deviations of the performance function are computed. With the proposed method, the impact of both random and interval variables on the system robustness can be evaluated efficiently.
3D Shape Classification Based on Spectral Function and MDS Mapping
Authors: Chen Zhanqing , Tang Kai
Published: March 2010

This paper reports a new method for 3D shape classification. Given a 3D shape M, we first define a spectral function at every point on M that is a weighted summation of the geodesics from the point to a set of curvature-sensitive feature points on M. Based on this spectral field, a real-valued square matrix is defined that correlates the topology (the spectral field) with the geometry (the maximum geodesic) of M, and the eigenvalues of this matrix are then taken as the fingerprint of M. This fingerprint enjoys several favorable characteristics desired for 3D shape classification, such as high sensitivity to intrinsic features on M (because of the feature points and the correlation) and good immunity to geometric noise on M (because of the novel design of the weights and the overall integration of geodesics). As an integral part of the work, we finally apply the classical multidimensional scaling method to the fingerprints of the 3D shapes to be classified. In all, our classification algorithm maps 3D shapes into clusters in a Euclidean plane that possess high fidelity to intrinsic features—in both geometry and topology—of the original shapes. We demonstrate the versatility of our approach through various classification examples.
Reverse Engineering: Statistical Threshold for New Selective Sampling Morphological Descriptor
Authors: Vezzetti E.
Published: March 2010

During the digitization process of a physical object, the operator has to choose an acquisition pitch. Currently, 3D scanners employ constant pitches. For this reason the grid dimension choice normally represents a compromise between the scanner performances and specific applications, and the resolution and accuracy of the specific application. This is a critical problem because, normally, the object shape is assumed as a combination of different geometries with different morphological complexities. As a consequence of this, while some basic geometries (i.e., planes, cylinders, and cones) require only few points to describe their behavior, others need much more information. Normally, this problem is solved with a significant operator involvement. Starting from the object morphology and from the 3D scanner performances, the author finds the optimal acquisition strategy with an iterative and refining process made of many attempts. This approach does not guarantee an efficient acquisition of the object, because it depends strongly on the subjective ability of the operator involved in the acquisition. Many approaches propose points cloud management methodologies that introduce or erase punctual information, working with statistical hypothesis after the acquisition phase. This research work proposes an operative strategy, which starts from, first, a raw point acquisition, then it partitions the object surface, identifying different morphological zone boundaries (shape changes). As a consequence, some of the identified regions will be redigitized with deeper scansions in order to reach a more precise morphological information. The proposed partitioning methodology has been developed to directly interact with the 3D scanner. It integrates the use of a global morphological descriptor (Gaussian curvature), managed in order to be applicable in a discrete context (points cloud), with the concept of the 3D scanner measuring uncertainty. This integration has been proposed in order to provide an automatic procedure and a “curvature variation threshold,” able to identify real significant shape changes. The proposed methodology will neglect those regions where the shape changes are only correlated with the uncontrolled noise introduced by the specific 3D scanner performances.
Reliability of Switched Model-Based Controller for Vessel Dynamic Positioning With Switching Under Estimated Motion Frequency
Authors: Nguyen Dong T. , Quek Ser Tong
Published: March 2010

In switched-control methodology, which integrates several controllers handling different environmental conditions for dynamic positioning (DP) systems in marine vessels, the supervisor uses the estimated wave peak frequency (WPF) to classify the existing environmental condition so as to switch to the appropriate controller. The WPF is assumed to be the same as the peak frequency of the vessel’s response spectrum at wave frequency estimated by fast Fourier transform (FFT) of the measured position and heading. Using a short window width leads to error in the WPF estimation whereas a longer width causes a significant time lag in control activation. This paper addresses the effect of uncertainty in the estimation of WPF by FFT on the reliability of the switched-controller based DP vessel. The probability of the supervisor switching to a wrong controller due to WPF estimation error is first evaluated for four different environmental conditions. The failure probabilities of the system with and without WPF uncertainty are then evaluated and compared. Numerical simulation based on a supply vessel shows that the increase in failure probability of the switched-controller DP system due to the uncertainty in the estimated WPF by FFT is not significant compared with the failure probability of a perfect switched-controller DP system.
Linear and Nonlinear Wave Models Based on Hamilton’s Principle and Stream-Function Theory: CMSE and IGN
Authors: Kim J. W. , Ertekin R. C. , Bai K. J.
Published: March 2010

Recently, two wave models based on the stream-function theory have been derived from Hamilton’s principle for gravity waves. One is the irrotational Green–Naghdi (IGN) equation and the other is the complementary mild-slope equation (CMSE). The IGN equation has been derived to describe refraction and diffraction of nonlinear gravity waves in the time domain and in water of finite but arbitrary bathymetry. The CMSE has been derived to consider the same problem in the (linear) frequency domain. In this paper, we first discuss the two models from the viewpoint of Hamilton’s principle. Then the two models are applied to a resonant scattering of Stokes waves over periodic undulations, or the Bragg scattering problem. The numerical results are compared with existing numerical predictions and experimental data. It is found here that Level 3 IGN equation can describe Bragg scattering well for arbitrary bathymetry.
Resonant states and transmission coefficient oscillations for potential wells and barriers
Authors: Maheswari A. Uma , Prema P. , Shastry C. S.
Published: March 2010

The oscillatory behavior of the transmission coefficient T as a function of energy is examined for an attractive square well and a rectangular barrier. We calculate T using resonant state boundary conditions and demonstrate that the maxima in T are correlated with the broad resonances generated by these potentials. For barrier potentials the maxima signify resonances occurring at energies above the barrier height. It is shown that the resonance position and width can also be generated from the complex poles of the amplitude of the transmitted plane wave. We also explain the relation between the positions of the resonances generated by the square well and the rectangular barrier to the energy eigenvalues of the corresponding rigid box with the same range. We show for a potential with an attractive well and a repulsive barrier that T exhibits oscillations when the particle energy is below the barrier, implying that in many cases the simple WKB type barrier penetration expression for T is not adequate. These features of T are likely to hold for most attractive potentials and flat repulsive barriers. We also discuss the attractive modified Poschl–Teller type potential for which T does not show oscillations as a function of energy.
A primer on the carbon cycle
Authors: Fano Guido
Published: March 2010

The atmosphere-ocean carbon cycle with particular attention to the residence time of CO2 in the atmosphere is clarified using a set of elementary box models along the lines of Schmitz. The coupling between surface of the ocean and the atmosphere is discussed using linear and nonlinear models. The different behavior of C12O2 and C14O2 is clarified. The diffusion of carbon dioxide in the deep ocean is briefly discussed.
Toward Extracting All Phylogenetic Information from Matrices of Evolutionary Distances
Authors: Roch Sebastien
Published: March 2010

Theoretically Speedy Trees

Phylogenetic tree construction often uses distance matrix methods, which offer promising scalable methods for rapid building of very large phylogenies. It has generally been assumed that trees constructed from distance matrices are intrinsically less accurate than those inferred from maximum likelihood methods, but the latter are slower to make.Roch(p.1376; see the Perspective byAllman and Rhodes) theoretically examined this problem and showed that distance methods can achieve the same level of accuracy as likelihood methods. Thus, the generally assumed tradeoff between accuracy and speed in phylogenetic reconstruction can be overcome.
The Puzzling Rise and Fall of a Dark-Horse Alzheimer's Drug
Authors: Miller Greg
Published: March 2010

The announcement last week that a closely watched phase III clinical trial for Alzheimer's disease had failed to show a significant effect deals yet another demoralizing blow to patients, families, and caregivers.
The Road We Must Take: Multidisciplinary Team Science
Authors: Disis Mary L. , Slattery John T.
Published: March 2010

Solutions to today's complex health problems will require
multidisciplinary innovative thinking and collaboration.
MHC Heterozygote Advantage in Simian Immunodeficiency Virus–Infected Mauritian Cynomolgus Macaques
Authors: O’Connor Shelby L. , Lhost Jennifer J. , Becker Ericka A. , Detmer Ann M. , Johnson Randall C. , MacNair Caitlin E. , Wiseman Roger W. , Karl Julie A. , Greene Justin M. , Burwitz Benjamin J. , Bimber Benjamin N. , Lank Simon M. , Tuscher Jennifer J. , Mee Edward T. , Rose Nicola J. , Desrosiers Ronald C. , Hughes Austin L. , Friedrich Thomas C. , Carrington Mary , O’Connor David H.
Published: March 2010

This manuscript demonstrates unambiguous major histocompatibility complex heterozygote advantage in macaque monkeys infected with the same strain of simian immunodeficiency virus, suggesting that a prophylactic HIV vaccine should elicit a population of CD8
+
T cells with broad specificity.
Is a Painless Labor Possible?
Authors: Cheng Elaine
Published: March 2010

Chemical permeation enhancers increase the effectiveness of lidocaine derivatives, conferring prolonged analgesia without motor impairment.