Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior.

Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.

Experimental inoculation of pregnant swine with type 1 bovine viral diarrhoea virus.

The ability of bovine viral diarrhoea virus type 1 (BVDV-1) to induce transplacental infection in pigs was evaluated. Control pigs (n = 4) were sham-inoculated while infected pigs (n = 4) were intranasally inoculated with BVDV-1 on day 65 of gestation. Blood samples were tested throughout the study for BVDV and antibody to BVDV. On day 110 of gestation, a Caesarean section was performed. Serum was obtained for virus isolation and antibody determination from all piglets, and all experimental animals were killed. Tissues were collected for virus isolation and histopathology. Bovine viral diarrhoea virus was isolated on days 5 and 7 after infection and seroconversion was demonstrated in all infected gilts; however, BVDV was only isolated from one fetus from an infected pig. Viraemia and seroconversion were demonstrated in the pregnant gilts; however, transplacental infection at day 65 of gestation in the pig was not consistently demonstrated.

Concentration of cardiac troponin I in a horse with a ruptured aortic regurgitation jet lesion and ventricular tachycardia.

An 18-year-old Thoroughbred gelding was evaluated because of sudden onset of ventricular tachycardia and signs of colic. Three years earlier, a diastolic decrescendo murmur, consistent with aortic regurgitation, had been detected, but the horse continued to perform well and compete successfully. Cardiac ultrasonographic examination revealed a defect in the interventricular septum below the aortic root, and serum concentrations of cardiac troponin I (cTnI) were higher than those measured in clinically normal horses. Repeated development of tachyarrhythmia during hospitalization prompted a decision to euthanatize the horse. A ruptured endocardial jet lesion below the aortic valve with formation of a cleft into the interventricular septum was found on necropsy. This report of increased serum cTnI concentrations in a horse with myocardial disease and our other findings suggest that assessment of cardiac troponin concentrations may be a useful tool in the evaluation of horses with suspected myocardial disease.

Characterization of eae+ Escherichia coli isolated from healthy and diarrheic calves.

Strains of Escherichia coli from 101 healthy and 114 diarrheic calves were screened by PCR for the eae (intimin) gene and Shiga toxin genes (stx). Each eae+ and eae/stx+ strain was examined for antimicrobial susceptibility, enterohemolysin activity, and the somatic O antigen was determined. An immunoassay was used to detect Shiga toxin antigens for the eae/stx+ E. coli. Significantly more (p = 0.005) of the healthy calves carried eae+ and eae/stx+ E. coli in their feces when compared to strains from diarrheic calves. Moreover, Shiga toxin antigens were detected significantly more (p = 0.001) often among the eae/stx+ strains from healthy calves when compared to eae/stx+ strains from diarrheic calves. However, significantly more (p = 0.001) of the eae+ and eae/stx+ strains from diarrheic calves were resistant to at least one of the antimicrobials tested, and the strains from diarrheic calves had a significantly (p = 0.05) higher rate of antimicrobial resistance to at least two different antimicrobial classes. No significant difference (p> or =0.05) was detected among the eae+ and eae/stx+ strains from healthy and diarrheic calves for enterohemolysin production. Serogroups O-negative, O5, O26, and O111 were predominate among both healthy and diarrheic calves.

Comparison of type I and type II bovine viral diarrhea virus infection in swine.

Some isolates of type II bovine viral diarrhea virus (BVDV) are capable of causing severe clinical disease in cattle. Bovine viral diarrhea virus infection has been reported in pigs, but the ability of these more virulent isolates of type II BVDV to induce severe clinical disease in pigs is unknown. It was our objective to compare clinical, virologic, and pathologic findings between type I and type II BVDV infection in pigs. Noninfected control and BVDV-infected 2-month-old pigs were used. A noncytopathic type I and a noncytopathic type II BVDV isolate were chosen for evaluation in feeder age swine based upon preliminary in vitro and in vivo experiments. A dose titration study was performed using 4 groups of 4 pigs for each viral isolate. The groups were inoculated intranasally with either sham (control), 10(3), 10(5), or 10(7) TCID50 of virus. The pigs were examined daily and clinical findings were recorded. Antemortem and postmortem samples were collected for virus isolation. Neither the type I nor type II BVDV isolates resulted in clinical signs of disease in pigs. Bovine viral diarrhea virus was isolated from antemortem and postmortem samples from groups of pigs receiving the 10(5) and the 10(7) TCID50 dose of the type I BVDV isolate. In contrast, BVDV was only isolated from postmortem samples in the group of pigs receiving the 10(7) TCID50 dose of the type II BVDV isolate. Type I BVDV was able to establish infection in pigs at lower doses by intranasal instillation than type II BVDV. Infection of pigs with a type II isolate of BVDV known to cause severe disease in calves did not result in clinically apparent disease in pigs.

Biopsy mineral analysis by inductively coupled plasma-atomic emission spectroscopy with ultrasonic nebulization.

Liver copper concentration is generally considered the best measure of copper nutritional status in cattle. Ultrasonic nebulization in conjunction with inductively coupled plasma-atomic emission spectroscopy (ICP-AES) was investigated as a method to provide adequate sensitivity to allow accurate simultaneous measurement of copper and 14 additional elements from needle biopsy samples. The element concentration frequency distribution profile of 12 elements routinely present in liver was compared to profiles of the elements in fat, muscle, vena cava, kidney, and clotted blood. The profiles could be used to confirm the authenticity of the liver biopsy sample. Element concentrations in biopsy samples taken in triplicate from the five lobes of a bovine liver were compared to those from triplicate wedge sections taken adjacent to the biopsies and analyzed by conventional ICP-AES. Precision between biopsies was equal to or better than precision between wedge samples. Some element concentrations determined by the biopsy procedure differed statistically from those determined by the wedge procedure, but differences were not sufficient to influence clinical interpretation of data.

Otitis media in preweaned Holstein dairy calves in Michigan due to Mycoplasma bovis.

Mycoplasma bovis was isolated from the tympanic bullae of dairy calves with an exudative otitis media. The history, clinical signs, gross and histologic lesions, and bacteriologic findings are described for 5 preweaned Holstein calves with otitis media from a 600-cow dairy in Michigan. Clinical findings consisted of unilateral or bilateral ear droop, epiphora, head tilt, and recumbency in severely affected calves. Postmortem examination revealed unilateral or bilateral fibrinosuppurative to caseous exudate in the tympanic bullae. Histologically, a marked fibrinosuppurative to caseous exudate filled the tympanic air spaces. The partially ulcerated tympanic mucosa was markedly thickened with mononuclear cell infiltration and proliferation of fibrous connective tissue. Bone remodeling and periosteal hyperostosis were present in some osseous septa. Mycoplasma bovis was isolated from the tympanic bullae of all 5 calves and from the lungs of 2 calves and the frontal sinus of 1 calf. Mycoplasma bovis was isolated at > 100,000 colony forming units/ml from the bulk milk tank of the farm of origin. The isolation of M. bovis from the bulk milk tank, indicating subclinical mycoplasmal mastitis coupled with the feeding of waste milk from mastitic cows to calves is suggestive of a possible source of the infection resulting in otitis media in preweaned dairy calves.

Prevalence of teaching apical patency and various instrumentation and obturation techniques in United States dental schools.

Maintaining an open apex beyond the apical constriction with an endodontic file during canal instrumentation is a concept that has been advocated by several authors and clinicians. To ascertain the prevalence of teaching the patency concept as well as various instrumentation and obturation techniques in the United States dental schools, a survey was conducted. Forty-eight out of a total of 53 dental schools (91%) responded to the survey. Results indicate that 50% of the schools surveyed teach the concept of patency to their undergraduates or graduates or both; 83% teach a step-back instrumentation technique; and 89.6% teach lateral condensation of gutta percha as their primary obturation technique.

Association of perianal fistula and colitis in the German shepherd dog: response to high-dose prednisone and dietary therapy.

Twenty-seven German shepherd dogs with perianal fistulas and histological evidence of colitis were entered in a prospective clinical study to investigate the association between perianal fistula and colitis. Additionally, the response of perianal fistula disease to immunosuppressive doses of prednisone and an alternative protein diet was evaluated. All 27 cases completed the treatment protocol, and perianal fistulas completely resolved in nine (33.3%) cases, improved in nine cases, and remained unchanged in nine cases.

Immunohistochemical diagnosis of eastern equine encephalomyelitis.

An immunohistochemical (IHC) assay was developed for the detection of eastern equine encephalomyelitis (EEE) virus antigen in formalin-fixed, paraffin-embedded tissues. All cases of EEE diagnosed at the Michigan State University Animal Health Diagnostic Laboratory from 1991 through 1994 were evaluated. The diagnosis was based on histopathologic examination of the brain and confirmatory virus, isolation. Sections of cerebrum from 26 equids and 5 birds were assessed by IHC. Histologically normal brain tissues from 2 horses and 1 pheasant and brain tissues from 2 cases of equine neurologic disease with diagnoses other than EEE served as negative controls. The IHC assay was based on standard streptavidin-biotin technology, using a commercially available kit and a monospecific polyclonal primary antibody preparation derived from murine ascitic fluid. Nineteen of 20 equids and all 5 birds positive by histopathology and virus isolation were positive for EEE virus antigen by IHC. Three equids with histologic lesions compatible with a diagnosis of EEE but negative by virus isolation also were negative for virus antigen by IHC. In 3 other equids, histopathology and IHC were positive for EEE, but virus isolation was not attempted because of contamination of the brain specimen. The IHC assay of formalin-fixed, paraffin-embedded brain tissues for EEE virus antigen is a rapid, effective test for confirming a histopathologic diagnosis of EEE, and assay results correlate well with virus isolation results.

A mechanical auxiliary ventricle. Histologic responses to long-term, intermittent pumping in calves.

The mechanical auxiliary ventricle (MAV) is an avalvular, inseries left ventricular assist device (LVAD) comprised of a 60 cc Biomer blood pump implanted in the descending thoracic aorta, a percutaneous access device (PAD), and an external pneumatic drive. In four calves the MAV was implanted and activated intermittently for 192, 249, 423, and 785 days, respectively; no anticoagulants were administered. When the animals were killed, the implants were retrieved, and autopsies, including gross, light microscopic, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) examinations, were performed. The MAV was securely attached to the aorta in every animal. A thin, even smooth, pseudoneointimal layer (PNI) contiguous with the aorta at the level of the suture line covered the MAV's blood-contacting surface. Areas of calcification beneath the PNI, expected in growing animals with implanted pumping devices, were noted. At autopsy there was no evidence of thrombosis or infection in the regions of the blood pump or the PAD. These findings confirm the calves' benign histologic response to the MAV, and together with the results of hematologic and biochemiccal studies, and bench tests of system components being reported elsewhere, indicate the system's readiness for limited clinical investigation in selected patients with chronic congestive failure.

Polycystic hepatic disease, thoracic granular cell tumor and secondary hypertrophic osteopathy in a horse.

A 13-year-old American Saddlebred mare was presented with a 4-day history of anorexia. Physical examination revealed increased inspiratory effort and bony enlargement of the distal limbs. Radiographs indicated a thoracic mass and periosteal proliferations on the distal limbs consistent with hypertrophic osteopathy. Gastric endoscopy revealed distal esophageal and gastric ulceration, and functional pyloric stenosis. Abdominal ultrasonographic examination revealed multiple large, cystic structures associated with the liver. A percutaneous biopsy indicated the thoracic mass to be a granular cell tumor. At necropsy, a large mass consisting of intercommunicating cystic structures was present confluent with the right caudal edge of the liver. Histologically these hepatic lesions were consistent with cystic hepatic disease, which has not previously been reported in the horse.

Characterization of acute 4,4'-methylene dianiline hepatotoxicity in the rat.

Methylene dianiline (DDM) is a chemical intermediate in the production of isocyanates and other industrial chemicals, and it is hepatotoxic in humans. The acute hepatotoxicity of orally administered DDM was characterized in rats. Rats receiving DDM (25-225 mg/kg, per os) demonstrated a dose-dependent elevation in serum alanine aminotransferase activity, g-glutamyltransferase activity, and serum bilirubin concentration. DDM also caused a decrease in bile flow and an elevation in liver weight. Significant changes in these markers of liver injury occurred between 8 and 12 hr after a single, oral administration of DDM. Histologically, DDM caused multifocal, necrotizing hepatitis with neutrophil infiltration. Changes in the portal regions consisted of bile ductular necrosis, portal edema, neutrophil infiltration, mild fibrin exudation, and segmental necrotizing vasculitis. The role of cytochrome P450 monooxygenase (MO)-mediated metabolism in DDM hepatotoxicity was evaluated using the MO inhibitors, aminobenzotriazole and SKF-525A and the MO inducers phenobarbital and beta-naphthoflavone. Aminobenzotriazole provided protection from DDM-induced hepatotoxicity, whereas SKF-525A had no effect. The effect of phenobarbital pretreatment depended on the dose of DDM administered. At a dose of DDM that produced a maximal hepatotoxic response, phenobarbital did not influence hepatotoxicity. However, phenobarbital pretreatment provided protection against the hepatotoxic effects of a lower dose of DDM. beta-naphthoflavone pretreatment had a more modest effect on DDM-induced hepatic insult. These results demonstrate that DDM causes acute hepatotoxicity in the rat that is dose and time dependent. Results using inducers and inhibitors of MO suggest that DDM requires bioactivation to exert toxicity; however, the relationship between metabolism and toxicity may be complex.

Lymphocytic/plasmacytic colitis in cats: 14 cases (1985-1990).

Lymphocytic/plasmacytic colitis was diagnosed in 14 cats during a 5-year period. Purebred cats were affected significantly (P < 0.001) more often than were nonpurebred cats. Six cats were male and 8 were female. Mean age at onset of clinical signs was 5.1 years (range, 0.5 to 9 years). Hematochezia, observed in 13 cats, was the most commonly reported sign; diarrhea was reported in 11 cats. Mildly high serum alanine transaminase activity and hypokalemia were frequent biochemical abnormalities. Campylobacter sp was cultured from the feces of 1 cat. On endoscopic examination, petechia and hyperemia of the colonic mucosa were detected in 7 of 8 cats. Cats were initially treated with dietary management alone or with a combination of dietary and pharmacologic management. Clinical signs in 7 of 11 treated cats completely resolved, whereas signs in 3 cats were considered improved. One cat was euthanatized when an inadequate response to treatment was observed. Most cats were eventually maintained on dietary management alone.

Use of zinc acetate to treat copper toxicosis in dogs.

Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs.

Lymphocytic/plasmacytic gastroenteritis in cats: 14 cases (1985-1990).

Over a 5-year period, lymphocytic/plasmacytic gastroenteritis was diagnosed in 14 cats. Purebred cats were affected significantly (P less than 0.025) more often than nonpurebred cats. Mean age at onset of clinical signs was 6.8 years (range, 1 to 13 years); 11 cats were male. Vomiting and weight loss, each reported in 10 of 14 cats, were the most common clinical signs. Diarrhea was reported in 7 of 14 cats. Alopecia was found in 4 of 14 cats. High hepatic enzyme activities and low plasma protein concentrations were frequent biochemical findings. Hyperemia, hemorrhage, and a roughened or "cobblestone" mucosa were visualized by endoscopy in only 2 of 8 cats with duodenal disease and in 2 of 5 cats with gastric disease. Lymphocytic/plasmacytic inflammation was detected in biopsy specimens from the stomach or duodenum or both in all cats; the duodenum was affected most commonly. Degree of inflammation frequently varied among gastric, duodenal, and colonic specimens from the same cat. Glucocorticoid treatment and dietary management adequately controlled clinical signs in 7 cats, but treatment was ineffective in 6 cats, 5 of which were euthanatized because of severity of clinical signs.

Pain control in endodontics.

Pain control in endodontics is paramount to patient acceptance of this special area of dental care. Alleviating existing pain is the primary objective of root canal therapy. This paper focuses on the control of pulp and periradicular pain at initial presentation and subsequent to the first visit.

Is endodontics losing its identity in our dental schools?

The program presented at the Section on Endodontics of the American Association of Dental Schools Annual Meeting in March 1990 in Cincinnati focused on the issue of identity loss of endodontics in dental schools. Program participants, comprising representatives from various institutions with different educational backgrounds and experiences, were posed a series of questions on the topic. Key issues were discussed and perspectives on the future of the specialty were presented relative to dental school reorganizations and restructuring.