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The article presents recommended guidelines for a standardized approach to sample submission, tissue trimming, margin evaluation and reporting of tumor biopsies in veterinary surgical pathology. It stresses the importance of the pathology report in determining prognosis, therapeutic decisions, and overall case management. It notes that the guidelines, prepared under the auspices of the American College of Veterinary Pathologists Oncology Committee, should be viewed as an evolving document requiring continuous revision.

The article presents a proposal for a two-tier histologic grading system for canine cutaneous mast cell tumors (MCTs) for a more accurate prediction of biological behavior. It evaluated the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system. The study showed significant interobserver variation in MCT grading among pathologists, suggesting unreliability in the current histologic grading system while the proposed system is found to offer higher consistency and less ambiguity.

The article tests the application of the World Health Organization (WHO) system for classification of canine malignant lymphomas by veterinary diagnosticians who were experienced but not expert in hematopathology. It describes malignant lymphoma as a disease that affects dogs of all breeds and ages and deemed the most common canine neoplasm treated by chemotherapy. Tissue biopsies were carried out on 300 cases and twenty pathologists were assessed on their diagnostic capabilities based on a list of 43 B and T cell lymphomas using the WHO system.

Background Canine adenovirus 2, parainfluenza, and Bordetella bronchiseptica cause respiratory disease in dogs, and each has a modified live intranasal vaccine available. Molecular diagnostic assays to amplify specific nucleic acids are available for each of these agents. If positive molecular diagnostic assay results are common after vaccination, the positive predictive value of the diagnostic assays for disease would be decreased. Objective To determine the impact of administration of commercially available modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza vaccine has on the results of a commercially available PCR panel. Animals Eight puppies from a research breeding facility negative for these pathogens. Methods Blinded prospective pilot study. Puppies were vaccinated with a single dose of modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza and parenteral dose of adenovirus 2, canine distemper virus, and parvovirus. Nasal and pharyngeal swabs were collected on multiple days and submitted for PCR assay. Results Nucleic acids of all 3 organisms contained in the topical vaccine were detected from both samples multiple times through 28 days after vaccination with higher numbers of positive samples detected between days 3 and 10 after vaccination. Conclusions and Clinical Importance Vaccine status should be considered when interpreting respiratory agent PCR results if modified live vaccines have been used. Development of quantitative PCR and wild-type sequencing are necessary to improve positive predictive value of these assays by distinguishing vaccinate from natural infection. [ABSTRACT FROM AUTHOR]

Objectives: To determine the ability to obtain diagnostic cytology samples from appendicular bone lesions using ultrasound-guided needle aspirations. Secondary objectives were to compare cytological evaluations with histopathological results and to determine the utility of staining malignant mesenchymal cells for the presence of alkaline phosphatase. Methods: Aspirations from 36 aggressive appendicular bone lesions with histological diagnoses were included in the study. Ultrasound was used to guide the needle to the medullary cavity or the adjacent soft tissue mass. The smears stained with Wright-Giemsa and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indoyl phosphate toluidine salt (NBT/BCIP) were examined. Results: A diagnostic sample was obtained in 32 of the 36 cases. Of the 32 diagnostic samples, cytology indicated sarcoma, with a sensitivity of 97 per cent (confidence interval: 83 to 100 per cent) and a specificity of 100 per cent (confidence interval: 16 to 100 per cent). When a diagnosis of sarcoma was made on cytology, alkaline phosphatase staining indicated osteosarcoma, with a sensitivity of 100 per cent (confidence interval: 87 to 100 per cent). Clinical Significance: The results of this study indicate that ultrasound-guided needle aspiration of aggressive bone lesions is a viable technique for identifying malignant mesenchymal cells and for diagnosing sarcomas. It is cost-effective and minimally invasive. Furthermore, identifying alkaline-phosphatase-negative malignant mesenchymal cells from a bone aspiration may rule out osteosarcoma, whereas alkaline-phosphatase-positive malignant mesenchymal cells are suggestive of osteosarcoma. [ABSTRACT FROM AUTHOR]

In summary, we have reported a most interesting case of synovial sarcoma, epithelial hyperplasia in the air sacs, and formation of medullary bone in the left humerus of a 5-year-old female white pigeon. The tumor showed aggressive features radiologically and caused dysfunction of the left wing. The histologic findings and immunohistochemical reactions in this report were identical in many respects to the manifestation of synovial sarcoma described in human beings and dogs. Formation of medullary bone in female birds during the reproductive phase and hyperplasia of epithelia in the air sacs were also discussed. [ABSTRACT FROM AUTHOR]

On April 22, CDC and the U.S. Department of Agriculture (USDA) reported cases of two domestic cats with confirmed infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). These are the first reported companion animals (including pets and service animals) with SARS-CoV-2 infection in the United States, and among the first findings of SARS-CoV-2 symptomatic companion animals reported worldwide. These feline cases originated from separate households and were epidemiologically linked to suspected or confirmed human COVID-19 cases in their respective households. Notification of presumptive positive animal test results triggered a One Health* investigation by state and federal partners, who determined that no further transmission events to other animals or persons had occurred. Both cats fully recovered. Although there is currently no evidence that animals play a substantial role in spreading COVID-19, CDC advises persons with suspected or confirmed COVID-19 to restrict contact with animals during their illness and to monitor any animals with confirmed SARS-CoV-2 infection and separate them from other persons and animals at home (1)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. David Smith reports grants and nonfinancial support from the USDA Animal and Plant Health Inspection Service, Veterinary Services, during the conduct of the study. No other potential conflicts of interest were disclosed.

Persistent infection of Anaplasma phagocytophilum (AP) after treatment and immunosuppression has not been studied in dogs infected with AP after Ixodes scapularis infestation. This descriptive pilot study evaluated 6 laboratory-reared beagles that were persistently positive for AP antibodies after infestation with wild-caught I. scapularis. After 20 weeks, 3 of 6 dogs were administered doxycycline orally for 28 days, and all 6 dogs were then administered prednisolone at 2.2 mg/kg orally for 14 days. Blood was collected from all 6 dogs and evaluated by complete blood count, AP antibodies, and AP DNA at the beginning of the study and on Week 24 through Week 28. Blood was collected from 5 of the dogs on Week 48. No dogs developed recognizable clinical signs of illness or clinically relevant complete blood count abnormalities. During Week 26 through Week 28, all 6 dogs were negative for AP DNA. On Week 48, the 2 doxycycline treated dogs available for testing were negative for AP DNA and antibodies; the 3 untreated dogs were negative for AP DNA but positive for AP antibodies. In this model, the prednisolone protocol used did not activate AP in dogs with chronic, vector-induced infection. Since PCR evidence of AP infection resolved in both groups of dogs, the effect doxycycline had in eliminating AP infection from I. scapularis-exposed dogs will require further study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We attempted to determine if Leptospira spp. antibodies induced by vaccination would cross-react with Borrelia burgdorferi antigens used in a commercial automated immunofluorescent assay (AccuPlex 4 BioCD; Antech). Staff- and student-owned dogs ( n = 31) were recruited at a veterinary teaching hospital in a B. burgdorferi nonendemic area. The dogs were randomized and administered 1 of 4 commercial Leptospira spp. vaccines that contained serovars Canicola, Grippotyphosa, Icterohaemorrhagiae, and Pomona, then booster vaccinated 3 wk later. Blood was collected on weeks 0, 3, 4, 8, and 12. After confirming that maximal Leptospira spp. titers occurred on week 4, aliquots of sera from week 4 were shipped frozen for analysis of B. burgdorferi antibodies against OspA, OspC, OspF, P39, and SLP with the AccuPlex system. Week 4 sera from all 31 dogs had a titer of 1:100 for at least 1 Leptospira spp. serovar. Titers of 1:800 or greater were detected against multiple serovars in 27 dogs. None of the samples contained antibodies against the B. burgdorferi OspA, OspC, OspF, P39, and SLP peptides used in the commercial assay. The B. burgdorferi peptides used in the AccuPlex system do not recognize naturally occurring Leptospira spp. antibodies or those induced by the commercial Leptospira spp. vaccines administered in our study.

Mast cell tumor (MCT) is the most common skin malignancy of domestic dogs and presents with a widely variable clinical behavior. Although activating KIT mutations are present in approximately 20% of canine MCTs, molecular etiology is largely unknown for the majority of this cancer. Characterization of genomic alterations in canine MCTs may identify genomic regions and/or genes responsible for their development and progression, facilitating the discovery of new therapeutic targets and improved clinical management of this heterogeneous cancer. We performed genome-wide DNA copy number analysis of 109 primary MCTs derived from three popular canine breeds (the Boxer, Labrador Retriever, and Pug) as well as nontarget breeds using oligonucleotide array comparative genomic hybridization (oaCGH). We demonstrated a stepwise accumulation of numerical DNA copy number aberrations (CNAs) as tumor grade increases. DNA sequencing analysis revealed that KIT mutations were found less frequently in the Pug tumors and were strongly associated with high histological grade. Tumors with KIT mutations showed genome-wide aberrant copy number profiles, with frequent CNAs involving genes in the p53 and RB pathways, whereas CNAs were very limited in tumors with wild-type KIT. We evaluated the presence of four CNAs to predict aggressive tumor phenotypes. This approach predicted aggressive tumors with a sensitivity of 78-94% and specificity of 88-93%, when using oaCGH and droplet digital PCR platforms. Further investigation of genome regions identified in this study may lead to the development of a molecular tool for classification and prognosis, as well as identification of therapeutic target molecules.

Objectives: Anaplasma phagocytophilum is an Ixodes species-transmitted rickettsial organism that is occasionally associated with clinical abnormalities in humans, ruminants, horses, dogs and cats. While serological evidence of A phagocytophilum exposure is common in cats in Ixodes species endemic areas, reports of clinical feline anaplasmosis are few. The objective of this study was to describe the clinical and laboratory abnormalities and treatment responses in 16 cats with A phagocytophilum DNA amplified from blood., Methods: Commercial laboratory electronic records were searched to find cats that had A phagocytophilum DNA amplified from their blood. Once cases were identified, the primary care veterinarian was interviewed and the medical records were reviewed., Results: The cats ranged in age from 4 months to 13 years (mean 4.1 years, median 2 years). All cats lived in Ixodes scapularis endemic areas and had potential for exposure. All cats were lethargic, 15 (94%) had elevated body temperature (>39.4°C) and 14 were anorexic on initial physical examination. Other less common clinical findings included hepatosplenomegaly, ataxia, conjunctivitis and elevation of the nictitating membranes. Blood from 11 cats was evaluated by complete blood cell count; abnormalities included lymphopenia in seven (64%) cats, thrombocytopenia in seven (64%), morulae in neutrophils of three (27%), neutropenia in three (27%) and leukopenia in two (18%). Treatment responses were reported for 14 cats, and the clinical abnormalities in these cats resolved when doxycycline was administered., Conclusions and Relevance: This is the first published report describing A phagocytophilum morulae in neutrophils of naturally infected North American cats with infection confirmed by PCR. A phagocytophilum infection should be considered in cats evaluated for lethargy, anorexia and fever living in Ixodes species endemic areas., (© ISFM and AAFP 2015.)

The primary objective of our study was to optimize detection of serum antibodies to Borrelia burgdorferi using a new commercial automated fluorescence system (Accuplex4 BioCD system, Antech Diagnostics, Lake Success, New York). The system used multiple natural and artificial peptides-outer surface proteins (OspA, OspC, OspF), an outer membrane protein (P39), and a proprietary synthetic peptide (small Lyme peptide [SLP])-and the results were compared with a commercially available enzyme-linked immunosorbent assay that uses a proprietary peptide (C6). Sera from 4 groups were evaluated: dogs vaccinated with 1 of 3 commercially available vaccines (n = 18); dogs infested with adult Ixodes scapularis (black-legged tick; n = 18); dogs previously vaccinated and then infested with I. scapularis (n = 18); and dogs with B. burgdorferi infection that were then vaccinated (n = 14). All of the vaccines evaluated induced OspA responses. However, antibodies against OspF or C6 were not induced in any of the vaccinated dogs. Additionally, the OspF antibodies had 100% sensitivity and specificity when compared to antibodies against C6 peptide. In B. burgdorferi-infected dogs, antibodies against OspC and SLP were detected in serum sooner than antibodies against the other targets. Low levels of antibodies against OspA developed in 6 of 14 B. burgdorferi-infected, unvaccinated dogs and had the shortest duration compared to the other antibodies. Detection of antibody responses to multiple B. burgdorferi targets with this system can be used to help differentiate vaccinated dogs from exposed dogs as well as acute infection from chronic infection., (© 2015 The Author(s).)

Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3-17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.

Infection with Anaplasma phagocytophilum can cause significant illness in some dogs and accurate diagnostic assays are needed. The objectives of the study were to optimize an automated fluorescence system for the detection of antibodies against A. phagocytophilum in canine serum. Serum and blood was collected temporally from seven dogs inoculated parenterally with culture-derived A. phagocytophilum and from 36 dogs exposed to wild-caught, adult Ixodes scapularis for 7 days. The system was optimized using the samples from the parenterally inoculated dogs. The ability to detect antibodies against A. phagocytophilum in the I. scapularis exposed dogs by the automated system was compared with a diagnostic kit (ELISA) and an indirect fluorescent antibody assay (IFA). Each blood sample was also assayed for A. phagocytophilum DNA by polymerase chain reaction (PCR). Of the 36 dogs exposed to I. scapularis, A. phagocytophilum DNA was amplified from blood from 22 dogs by PCR with first positive results occurring on weeks 1 (seven dogs), 2 (nine dogs), 3 (four dogs), 4 (one dog), or 5 (one dog). PCR results were positive prior to detection of antibodies in any of the three antibody assays for 19 dogs. The automated fluorescence system and IFA detected antibodies against A. phagocytophilum earlier than the ELISA. In conclusion, A. phagocytophilum PCR assays on blood are indicated in dogs with suspected acute anaplasmosis if serum antibody assays are negative., (Copyright © 2014. Published by Elsevier Ltd.)

Ehrlichia canis is the most common cause of monocytotropic ehrlichiosis in dogs around the world. The purpose of the present study was to validate a new automated fluorescence system (Accuplex4™ BioCD system; Antech Diagnostics, Lake Success, New York) to detect antibodies against the E. canis immunodominant glycoprotein 36 (gp36). Sera and blood samples (ethylenediamine tetra-acetic acid) were collected from mixed sex beagles ( n = 8) on days 0, 3, 7, 10, 14, 17, 21, 28, 42, 49, 56, 63, 70, 77, 84, and 98 after intravenous inoculation with culture-derived E. canis. Sera were assayed using the Accuplex4 BioCD system (Accuplex4), an E. canis indirect fluorescent antibody test (IFAT), and a commercially available kit. A complete blood cell count and a proprietary E. canis polymerase chain reaction (PCR) were performed on each blood sample. On the day thrombocytopenia was first detected for each dog, E. canis DNA was amplified from blood of all dogs. At those times, E. canis antibodies were detected in 7 of 8 dogs by the Accuplex4, 1 of 8 dogs by the commercial kit, and 4 of 8 dogs by IFAT. Ehrlichia canis DNA was amplified from blood before seroconversion in any antibody assay for 6 dogs. Antibodies against gp36 were detected by Accuplex4 within 3 days of PCR-positive test results and were detected up to 25 days sooner than the commercial kit. After starting doxycycline treatment, E. canis DNA was no longer amplified by PCR assay, but serum antibodies remained detectable by all assays.

There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists' Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association.

To determine the national, regional, and age-related prevalence of intestinal parasites in dogs presenting to veterinarians in the United States, we reviewed the results of examination via zinc sulfate centrifugal flotation of 1,199,293 canine fecal samples submitted to Antech Diagnostics in 2006. The most commonly identified intestinal parasites were ascarids (2.2%), hookworms (2.5%), whipworms (1.2%), Giardia (4.0%), and Cystoisospora (4.4%). With the exception of whipworms, intestinal parasites were more commonly identified in dogs less than 6 months of age (29.6% positive) as compared to those greater than 1 year of age (6.1% positive) although infections with each parasite considered were identified in all age classes of dogs. Hookworm eggs were most commonly identified in fecal samples submitted from dogs from the South (4.0% positive), whereas ascarid eggs and Giardia cysts were most commonly seen in samples from dogs from the West (2.8% and 6.3% positive, respectively). When compared to previous data from shelter dogs, the prevalence of intestinal helminths, particularly ascarids and hookworms, was greatly suppressed in pet dogs in the southern United States (90-91% reduction) and much less so in dogs in the West (52-78% reduction), perhaps due in part to the routine year-round use of monthly anthelmintics effective at controlling both heartworm infection and intestinal helminths in dogs in the South. Taken together these data indicate that intestinal parasites remain a common, important finding in dogs presenting to veterinary practices although in most of the country infection rates in pet dogs appear to be greatly reduced from the level reported from dogs in animal shelters.

Hepatic lipidosis in cats is a commonly diagnosed hepatobiliary disease of unknown cause. The purpose of this prospective study was to characterize the blood hormone and lipid status of cats with hepatic lipidosis, and to compare this status to that of cats with other types of liver disease and to control cats. Twenty-three cats with hepatic disease were assigned to 1 of 2 groups on the basis of cytopathologic or histopathologic examination of the liver: group 1, hepatic lipidosis (n = 18); or group 2, cholangiohepatitis (n = 5). Ten healthy young adult cats were used as controls. Food was withheld from control animals for 24 hours before blood collection. Concentrations of plasma glucagon and serum insulin, cortisol, thyroxine, triglycerides, cholesterol, phospholipids, and nonesterified fatty acids (NEFAs) were determined in all cats, in addition to routine hematologic and serum biochemical testing. Cats with hepatic lipidosis had higher serum NEFA concentrations than cats with cholangiohepatitis or control cats (P < .05). Cats with cholangiohepatitis had higher serum cholesterol and phospholipid concentrations than those of cats with lipidosis or control cats (P < .05); their plasma glucagon concentrations were higher than those of control cats (P < .05), but were not different from those of cats with hepatic lipidosis. Serum insulin concentrations were significantly higher in control cats than in diseased cats (P < .05), but neither serum insulin nor the insulin to glucagon ratio was significantly different among the cats with hepatic disease. The high concentration of NEFAs in cats with hepatic lipidosis suggests that at least 1 factor in the pathogenesis of this syndrome may involve the regulation of hormone-sensitive lipase.

To determine the accuracy of intraoperative cytopathological diagnosis compared with conventional histopathological diagnosis, the authors obtained 100 specimens from masses of various organ systems chosen randomly from 65 dogs, 30 cats, and five exotic animals. Of the 100 specimens, a specific diagnosis was obtained in 42%, the correct pathological process (i.e., mesenchymal neoplasia, epithelial neoplasia, round cell neoplasia, or inflammation) was identified in 41%, in 1% the diagnosis was deferred, and in 16% an incorrect diagnosis was obtained. The overall accuracy rate of intraoperative cytopathological examination was 83%, which increased to 90% by the exclusion of splenic masses. The accuracy rate of diagnosing neoplasia was 87%, with a sensitivity of 89% and a specificity of 100%. Intraoperative cytopathological examination is an accurate diagnostic method with good sensitivity and specificity for the identification of neoplasia.

Purpose: To test whether global ratings of checklists are a viable alternative to global ratings of actual clinical performance for use as a criterion for standardized-patient (SP) assessment., Method: Five faculty physicians independently observed and rated videotaped performances of 44 medical students on the seven SP cases that comprise the fourth-year assessment administered at The Morchand Center of Mount Sinai School of Medicine to students in the eight member schools in the New York City Consortium. A year later, the same panel of raters reviewed and rated checklists for the same 44 students on five of the same SP cases., Results: The mean global ratings of clinical competence were higher with videotapes than checklists, whereas the mean global ratings of interpersonal and communication skills were lower with videotapes. The correlations for global ratings of clinical competence showed only moderate agreement between the videotape and checklist ratings; and for interpersonal and communication skills, the correlations were somewhat weaker., Conclusion: The results raise serious questions about the viability of global ratings of checklists as an alternative to ratings of observed clinical performance as a criterion for SP assessment.

Limited information is available on prognostic factors for cats with lymphoma. The quantity of argyrophilic nucleolar organizer region (AgNOR) proteins can be used as a measurement of cellular proliferative activity. To determine if AgNORs were of prognostic value for feline intestinal lymphoma, the silver staining technique was performed on paraffin-embedded sections of 31 cases. Mean number of AgNORs per nucleus ranged from 1.02 to 4.32. Twenty-four (78%) cats had small AgNORs and 7 (22%) had large AgNORs. All cats were treated identically with a combination chemotherapy protocol. Response to chemotherapy was 87%. Median remission duration and survival times were 120 days and 201 days, respectively. No significant correlation was found between mean number of AgNORs per nucleus or AgNOR size and remission rate, remission duration, or survival time. This study indicates that AgNOR staining is not a useful prognostic factor for cats with intestinal lymphoma.

Purpose: To test the criterion validity of existing standardized-patient (SP)-examination scores using global ratings by a panel of faculty-physician observers as the gold-standard criterion; to determine whether such ratings can provide a reliable gold-standard criterion to be used for validity-related research; and to encourage the use of these gold-standard ratings for validation research and examination development, including scoring and standard setting, and for enhancing understanding of the clinical competence construct., Method: Five faculty physicians independently observed and rated videotaped performances of 44 students from one medical school on the seven SP cases that make up the fourth-year assessment administered at The Morchand Center of Mount Sinai School of Medicine to students in the eight member schools in the new York City Consortium., Results: The validity coefficients showed correlations between scores on the examination and the overall ratings ranging from .60 to .70. The reliability coefficients for ratings of overall examination performance reached the commonly recommended .80 level and were very close at the case level, with interrater reliabilities generally in the .70 to .80 range., Conclusion: The results are encouraging, with validity coefficients high enough to warrant optimism about the possibility of increasing them to the recommended .80 level, based on further studies to identify those measurable performance characteristics that most reflect the gold-standard ratings. The high interrater reliabilities indicate that faculty-physician ratings of performance on SP cases and examinations can or may be able to provide a reliable gold standard for validating and refining SP assessment.

Objective: To evaluate clinical, laboratory, radiographic, ultrasonographic, surgical, and histologic findings in ferrets with insulinoma and to determine their long-term outcome., Design: Retrospective study., Animals: 57 ferrets with a histopathologic diagnosis of pancreatic islet cell tumor., Procedure: Medical records of ferrets with pancreatic islet cell tumors were reviewed., Results: Lethargy, weakness, and collapse were the most common clinical signs. All ferrets had hypoglycemia, and hyperinsulinemia was documented in 39 of 47 (83%) ferrets. Ultrasonographic examination of the abdomen revealed pancreatic nodules in 5 of 23 ferrets. Surgical treatment was performed in 50 ferrets, 3 were treated by medical management alone, and 4 did not have treatment. At the time of surgery, 1 pancreatic nodule was found in 13 (26%) ferrets and multiple nodules were found in 37 (74%) ferrets. Pancreatic carcinoma alone was found in 34 ferrets. Whereas a combination of carcinoma and either hyperplasia or adenoma was found in 23 ferrets; 4 ferrets had metastasis to regional lymph nodes or liver. In 26 (53%) ferrets, hypoglycemia persisted after surgery, necessitating medical treatment with prednisone, diazoxide, or both. Sixteen (33%) ferrets had redevelopment of hypoglycemia at 1 to 23.5 months (median, 10.6 months) after surgery. Only 7 of the 50 (14%) ferrets remained euglycemic after surgery., Clinical Implications: In ferrets, surgical removal of insulin-secreting pancreatic islet cell tumors is recommended as definitive treatment; however, multiple pancreatic nodules are common, making complete excision of all tumor tissue difficult. Persistent hypoglycemia after surgical treatment indicates that lifelong medical management with prednisone or diazoxide or both may be necessary in many ferrets. Finally, because the insulin-secreting tumors are malignant, long-term cure and survival are not likely.

The purpose of this study was to evaluate fructosamine concentrations in clinically healthy cats, sick cats with stress hyperglycemia, and untreated diabetic cats to determine the usefulness of this test in diagnosing diabetes mellitus in cats, and in differentiating the disease from stress-induced hyperglycemia. In addition, we evaluated if the degree of glycemic control in cats treated for diabetes influenced their serum fructosamine concentrations. In the 14 sick cats with stress hyperglycemia, the median serum fructosamine concentration (269 mumol/L) was not significantly different from the median value in the 26 clinically normal cats (252 mumol/L). Two of the 14 cats with stress hyperglycemia (14.3%) had serum fructosamine concentrations above the upper limit of the reference range (175 to 400 mumol/L); on the basis of these results, the test specificity was calculated as 0.86. In 30 cats with untreated diabetes mellitus, the median serum fructosamine concentration was 624 mumol/L, markedly higher than the value in either the normal cats or the cats with stress hyperglycemia. All but 2 of the 30 untreated diabetic cats (6.7%) had serum fructosamine concentration above the upper limit of the reference range; on the basis of these results, the sensitivity of serum fructosamine concentration as a diagnostic test for diabetes mellitus was 0.93. When 30 diabetic cats receiving treatment were divided into 3 groups according to their response to treatment (i.e., poor, fair, and good), the 16 cats that had a good response to treatment had significantly lower serum concentrations of both glucose and fructosamine compared with cats that had either a fair or poor response to treatment. A significant correlation (rs = .70, n = 100, P < .001) was found between serum concentrations of glucose and fructosamine. Results of this study indicate that quantification of serum fructosamine concentration is a meaningful test for the diagnosis of diabetes, for differentiating diabetes from stress hyperglycemia; and for monitoring the metabolic control in treated diabetic cats.

Medical records of 117 dogs with digit masses were reviewed. Of 124 digit masses, 76 (61%) were malignant neoplasms, 25 (20%) were benign neoplasms, and 23 (19%) were pyogranulomatous inflammation. Of 29 digits with radiographic evidence of bone lysis, 24 (83%) were affected by malignant masses, whereas only 5 of 29 (17%) digits with radiographic evidence of bone lysis were affected by benign or pyogranulomatous masses. Only 1 of 19 (5%) dogs with melanoma had radiographic evidence of lysis, but 20 of 25 (80%) dogs with squamous cell carcinoma had radiographic evidence of bone lysis. Thoracic radiographs of 95 dogs were available. Six of 19 (32%) dogs with melanoma had radiographic evidence of pulmonary metastasis at the time of diagnosis, whereas 3 of 24 (13%) dogs with squamous cell carcinoma had radiographic evidence of pulmonary metastasis at the time of diagnosis. Twenty-nine digit neoplasms were squamous cell carcinoma, and 19 of 29 (66%) arose from the subungual epithelium. Of 19 dogs with squamous cell carcinoma originating from the subungual epithelium, 18 (95%) survived for at least 1 year, whereas only 6 of 10 (60%) dogs with squamous cell carcinoma originating in other parts of the digit survived for at least 1 year. Furthermore, of 19 dogs with squamous cell carcinoma originating from the subungual epithelium, 14 (74%) survived at least 2 years, whereas only 4 of 9 (44%) dogs with squamous cell carcinoma originating in other parts of the digit survived for 2 years. Dogs with melanoma of the digits had a median survival time of 12 months, with 10 of 24 (42%) alive at 1 year and 3 of 23 (13%) alive at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Scoring protocols for most standardized-patient (SP) examinations have not received extensive scrutiny and their validity has not been well established., Method: A holistic method (i.e., one based on raters' overall impressions) of scoring performance on an SP examination was pilot-tested in the spring of 1992 by administering an examination to two cohorts of fourth-year students at the Albert Einstein College of Medicine at Yeshiva University. The examination consisted of eight SP stations, representing a range of medical problems. Two to three experienced clinical teachers independently reviewed all the written material for each encounter. In Phase I of the study, holistic ratings of outstanding, competent, marginal, or inadequate were given for overall clinical competence for a cohort of 16 students; in Phase II, holistic ratings were given separately for data-gathering and communication skills for a cohort of 26 students. Intercase and interrater reliability analyses were performed., Results: Adequate reliability coefficients were obtained on a two-hour test; total scores (i.e., students' scores across all eight cases) discriminated between groups of examinees; and, on average, less than two minutes were required to score an encounter., Conclusion: Although based on a small sample, the study's results suggest that this holistic method of scoring performance may be useful in some situations. Since experienced clinical teachers know and agree about clinical competence when they see it, developers of scoring protocols for SP examinations need to establish that the results obtained are congruent with the judgments of expert teachers.

Adrenocortical adenoma, nodular hyperplasia, or carcinoma was diagnosed in 50 ferrets. Thirty-five (70%) ferrets were female and 15 (30%) were male. The mean age at which clinical signs were first noticed was 3.4 years (range, 1 to 7 years). Clinical signs included large vulva (n = 31; 89% of females), alopecia (n = 43; 86%), pruritus (n = 20; 40%), and increased consumption of water and increased urine output (n = 4; 8%). A mass was palpated at the cranial pole of the kidney during physical examination of 17 (34%) ferrets. Ultrasonography, performed on 39 of 50 ferrets, revealed a unilateral adrenal gland mass in 19 (49%). Four ferrets were anemic, and 2 ferrets were thrombocytopenic. Baseline plasma concentrations of cortisol and corticosterone were within or below the reference range in all 17 ferrets tested, whereas baseline plasma estradiol concentrations were high in 4 of the 11 ferrets (36%) tested. AFter adrenocorticotropic hormone (ACTH) administration, only 1 ferret had a slightly exaggerated response on the basis of plasma cortisol concentrations, and all 17 had normal responses on the basis of plasma corticosterone concentrations. There was little or no increase in plasma estradiol concentrations after ACTH administration. Of the 50 ferrets, 39 were treated by adrenalectomy. Unilateral adrenalectomy was performed in 34 ferrets in which 1 adrenal gland was large, whereas subtotal bilateral adrenalectomy was performed in 5 ferrets with bilateral adrenal disease. Five ferrets died in the immediate postoperative period, and follow-up information was available for the remaining 34, 1 to 34 months after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical records were reviewed for 18 cats with adenomatous polyps of the proximal portion of the duodenum. Cats of Asian ancestry were over represented (8/18), and male castrated cats were common (15/18). The median age was 11.8 years. Common clinical signs were acute and chronic vomiting and hematemesis. Nine cats were anemic. Contrast radiography was performed in 12 cats, and a mass of the proximal portion of the duodenum was identified in 10 cats. Endoscopy was used to confirm existence of the mass in 3 cats. Complete excision of the duodenal mass was performed in 17 cats. One cat died before abdominal exploratory surgery, and a duodenal adenomatous polyp was identified at necropsy. Fifteen cats survived the immediate postoperative period, with 13 of 15 having complete resolution of clinical signs. Five cats had concurrent disease, which caused 4 of them to die between 3 and 26 months after surgery. Redevelopment of adenomatous polyps was not detected in any cat during the follow-up period of 1 to 49 months. Results of the study indicated that benign, adenomatous polyps of the duodenum in cats can be safely excised and that the prognosis for return to normal function is excellent.

Forty-one cases of infiltrative urethral disease in female dogs were reviewed. The cause was epithelial neoplasia in 29 dogs, granulomatous (chronic active) urethritis in 10 dogs, and leiomyoma in 2 dogs. Clinical signs of disease were similar in dogs with neoplastic and inflammatory disease and included strangury (36/41), hematuria (30/41), pollakiuria (20/41), vaginal discharge (16/41), and complete urinary obstruction (7/41). Results of aspiration biopsy of the urethra correlated with those of surgical biopsy in 11 of 15 dogs. In 4 of 15 dogs, results of cytologic and histologic examinations differed. Granulomatous (chronic active) urethritis is an infiltrative urethral disease in female dogs. Clinical findings are similar, but the prognosis is more favorable than that in dogs with urethral epithelial neoplasia.

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).

The Raji cell radioimmunoassay was adapted to measure circulating immune complexes (CIC's) in the sera of 74 dogs with benign and malignant breast disease. In dogs with recently diagnosed spontaneous breast cancer, 57% (29 of 51) had elevated CIC's, with some levels as high as those found in the sera of dogs with systemic lupus erythematosus. The sera of 10 of 23 dogs with benign breast disease also demonstrated elevated levels of CIC's. Two weeks following mastectomy, repeat CIC levels were obtained in 30 dogs. Elevated CIC levels returned to normal in all dogs with benign breast disease but in only 33% of dogs with breast cancer. Dogs with persistent elevation of CIC's were at greater risk of developing metastatic breast cancer. Serum total hemolytic complement was significantly higher (p < 0.05) in dogs with untreated breast cancer than in healthy dogs but did not correlate with the level of CIC's found. Two weeks after mastectomy, total hemolytic complement levels had returned to normal. By sucrose density gradient ultracentrifugation, the complexes were shown to sediment at 19 S. These studies indicate that the dog may be a good model for elucidating the significance of elevated CIC's in breast cancer.

Two shar-pei puppies examined because of signs of sinopulmonary disease, one of which also had skin disease, had deficient IgA concentrations. Deficient serum IgA concentrations also were confirmed in 30 of 39 (76.9%) clinically normal adult dogs in two colonies of shar-peis. Both courses of disease--sinopulmonary signs and chronic skin disease and a benign clinical course--have been reported in human patients with IgA deficiency. Thus, the shar-pei might be an appropriate model for studying the immunopathology of IgA deficiency in man.

Improved survival resulting from advances in therapy in patients with Hodgkin's disease is associated with long-term morbidity, including the potential for the development of a second solid malignancy. We report a 44-year-old man with an unusually aggressive course of thyroid carcinoma 15 years after treatment for Hodgkin's disease. In a review of the English-language literature, we found 21 cases of thyroid cancer following radiotherapy for Hodgkin's disease, with latency periods ranging from 6 to 48 years. The development of secondary thyroid cancer after high-dose neck irradiation may be related to hypothyroidism, itself a complication of radiotherapy. Thyroid function should be measured at least once a year in all patients given neck irradiation, with initiation of thyroid hormone replacement if there is evidence of sustained hypothyroidism.