Amyloid deposition in 2 feline thymomas.

Two cases of feline thymoma with amyloid deposition were encountered between 1982 and 2010. Neoplastic cells were separated by abundant, pale eosinophilic, homogeneous material that was congophilic and birefringent. Ultrastructurally, the neoplastic cells were connected by desmosomes, and the extracellular deposits were composed of nonbranching, hollow-cored fibrils, 8-10 nm in diameter. In the case with sufficient archived tissue for additional sections, the amyloid remained congophilic following potassium permanganate incubation, and the neoplastic cells were immunoreactive for pancytokeratin. The histologic, histochemical, ultrastructural, and immunohistochemical features of both neoplasms are consistent with epithelial-predominant thymoma with the unusual feature of intratumoral amyloid deposition. The affinity of the amyloid for Congo red following potassium permanganate incubation is consistent with non-AA amyloid. The ultrastructural findings were consistent with amyloid production by the neoplastic epithelial cells.

Payment to healthy volunteers in clinical research: the research subject's perspective.

Although there is much discussion regarding the ethics of making payments to healthy volunteers for participating in clinical research, little data are available from the point of view of the volunteers as to what they would consider to be fair payment. The objectives of this study were to determine healthy volunteers' estimates of appropriate payments for participation in hypothetical clinical trials in order to explore the reasoning behind these estimates and to examine the association between volunteer demographics and payment expectations. Sixty participants with previous experience as healthy volunteers in research studies were presented with four hypothetical studies and interviewed about their impressions of burden and risks involved in the studies. They were also asked to estimate an appropriate payment to the volunteers for each of the studies. For each of the studies, the payment estimates made by the participants varied over a wide range. However, each individual tended to be consistent in estimate placement within this range. No demographic factor was significantly associated with the estimated study payment. Subjects frequently mentioned risk and logistical burden as factors that should determine payment levels. Healthy volunteer subjects appear to have individualized yet consistent methods of arriving at estimates of payments for participating in clinical studies. These estimates are based on each subject's perception of study burden and associated risk.

Disseminated Oxyporus corticola infection in a German shepherd dog.

The filamentous basidiomycetous fungus, Oxyporus corticola, has not previously been reported in the human or veterinary medical literature. Identification of this organism as the etiologic agent of fungal osteomyelitis and multiorgan dissemination in a German shepherd dog was confirmed by comparison of ITS and D1/D2 sequences with known isolates.

Multifocal rhabdomyosarcomas within the tongue and oral cavity of a dog.

A 10-year-old terrier crossbreed presented with a change in bark intonation of 3-4 month's duration and pronounced panting. Four variably sized masses were observed within the oral cavity. The largest mass was located within the parenchyma at the caudal region of the tongue. Others were located on the left arytenoid, within the soft palate, and in the oropharynx above the soft palate. Histopathologic specimens consisted of large round to polygonal cells occasionally containing multiple nuclei and rare faint cytoplasmic cross striations. Staining was weakly positive with periodic acid-Schiff. Immunocytochemistry was strongly diffusely positive for muscle-specific actin, myoglobin, and desmin and scattered positive for S-100 and vimentin. Phosphotungstic acid-hematoxylin staining enhanced cytoplasmic cross striations. The cytoplasm of all neoplastic cells was filled with mitochondria on electron microscopy. The final diagnosis was multifocal/metastatic rhabdomyosarcoma.

The prognostic significance of angiogenesis in canine mammary tumors.

The purpose of the study was to determine if neovascularization, a measure of angiogenesis, is correlated with metastasis of mammary tumors in dogs. Forty-six paraffin-embedded tissue blocks of benign and malignant canine mammary tumors obtained from 42 clinical cases at the Iowa State University Veterinary Teaching Hospital were retrieved from the archives of the Department of Veterinary Pathology. Of the dogs with malignant tumors, cases with and without lymph node metastasis were chosen. Neovascularization was quantified by light microscopy on formalin-fixed, paraffin-embedded sections of canine mammary tumors using an avidin biotin immunoperoxidase assay for factor VIII-related antigen. Mean microvessel counts for each group were statistically evaluated using analysis of variance. The mean number of microvessels was highest in the malignant tumors of dogs with lymph node metastasis (44). This number was significantly different from the mean number of microvessels in the benign tumors (28; P = .03) and a trend occurred toward higher microvessel counts in malignant tumors with lymph node metastasis versus malignant tumors of dogs without metastasis (32; P = .1). No significant difference was found between the number of microvessels found in malignant tumors without metastasis versus benign tumors. The trend toward higher microvessel counts in mammary tumors that have metastasized supports the premise that angiogenesis may be an independent and significant prognostic indicator in dogs with malignant mammary tumors, as it is in women with breast cancer.

Extraskeletal osteosarcoma of the mandibular salivary gland in a dog.

A 14-year-old spayed female shepherd/collie crossbred dog had a 6 x 4-cm mass excised from below the right ear. The partially encapsulated, neoplastic mass had a necrotic core and was embedded in the mandibular salivary gland. Histologically, the mass was composed of numerous multinucleate giant cells and large, oval, pleomorphic cells that produced osteoid. Neoplastic cells were immunoreactive for vimentin and actin but not for keratin, desmin, or S-100 protein. At postmortem examination 1 month later, an 11-cm spherical mass had recurred at the surgical site, and there were metastatic nodules in the lungs, ipsilateral mandibular lymph nodes, and kidney. The tumor was diagnosed as an osteosarcoma of the mandibular salivary gland with pulmonary, lymphatic, and renal metastasis. In addition, a 17-year survey of canine salivary-gland neoplasms revealed that most were adenocarcinomas or carcinomas.

Utility of portable chest radiographs as a predictor of endotracheal tube cuff pressure.

Increased endotracheal tube cuff pressure causes mucosal ischemia that can lead to necrosis, infection, and, eventually, tracheomalacia or tracheal stenosis. Endotracheally intubated patients frequently undergo portable chest radiography. In this study we explored the relationship of endotracheal tube cuff pressure and the appearance on the tracheal air columns on the portable chest radiograph. We measured the endotracheal tube cuff pressure of intensive care unit patients 124 times immediately before portable chest radiography. On 64 of these radiographs we measured the width of the tracheal air column below the tip of the endotracheal tube and at the maximal diameter of the endotracheal tube balloon. We then analyzed the relationship of cuff pressure to tracheal dilation. The results of ANOVA of tracheal dilation for three groups (safe, borderline, and unsafe cuff pressures) were significant. Large overlapping ranges existed in each group. Regression analysis confirmed a linear relationship between cuff pressure and tracheal dilation (r = 0.435, p < 0.001). Predicted tracheal expansion at 20 mm Hg was a poor screen for endotracheal tube cuff inflation safety; the sensitivity was only 56% and specificity only 71%. The differences in the capacity for tracheal distension between patients make these findings not unexpected. The portable chest radiograph is a poor screening tool for unsafe endotracheal tube cuff pressure.

Macrophage inflammatory protein-1beta (MIP-1beta) produced endogenously in brain during E. coli fever in rats.

Macrophage inflammatory protein-1 (MIP-1) evokes an intense fever, independent of a prostaglandin mechanism, and is now thought to play an important role in the defence response to bacterial pyrogens. The purpose of this study was 2-fold: (i) to determine whether the potent doublet of this cytokine, MIP-1beta, is actually produced in the brain in response to a pyrogenic dose of a lipopolysaccharide of Escherichia coli and (ii) to determine the anatomical site of synthesis of this cytokine in the brain. Following the intense fever produced by intraperitoneal administration of lipopolysaccharide in the unrestrained rat, MIP-1beta immunoreactivity was identified post mortem in two regions of the brain implicated in fever: the organum vasculosum laminae terminalis (OVLT) and the anterior hypothalamic, preoptic area (AH/POA). Microinjection of goat anti-mouse MIP-1beta antibody (anti-MIP-1beta) directly int the AH/POA markedly suppressed fever in rats in response to lipopolysaccharide. Further anti-MIP-1beta administered 180 min after the injection of lipopolysaccharide acted as an antipyretic and reversed the fever induced by the endotoxin. anti-MIP-1beta or control immunoglobulin G antibody microinjected into the hypothalamus immediately before the intraperitoneal injection of the control saline did not alter the temperature of the rats. Taken together, the present results demonstrate that MIP-1beta is produced in the brain in response to a bacterial endotoxin. These observations, in the light of earlier data on fever induced by MIP-1beta, further support the hypothesis that endogenously synthesized MIP-1beta acts as an intermediary factor in the evocation of fever by acting on the thermosensitive cells of the brain.

Uptake of ferritin and Bordetella avium in bronchus-associated lymphoid tissue of turkeys.

The uptake of macromolecular and particulate materials in bronchus-associated lymphoid tissue (BALT) in turkeys was examined using transmission electron microscopy. Tracer materials used were live and ultraviolet-killed (UV-killed) Bordetella avium and ferritin. Suspensions of bacteria and ferritin were instilled via intratracheal catheterization and allowed to remain in contact with the respiratory surfaces for 0, 10, 30, 60, 90, and 120 min. Ferritin and B. avium were taken up by both ciliated and non-ciliated cells of the epithelium overlying BALT (BALT epithelium). Ferritin was found in organelles associated with endocytosis (i.e. apical vesicles, endosomes, cytoplasmic vacuoles) and was apparently transported across epithelial cells, since it was also found in intercellular spaces. Bacteria were found in vacuoles within BALT epithelial cells, but not free in intercellular spaces. Some macrophages in BALT epithelium also contained bacteria. No differences were observed between uptake of live and UV-killed bacteria. We conclude that both ciliated and non-ciliated cells of BALT epithelium in turkeys are able to take up macromolecular and particulate materials. Bacteria are also accessible to intraepithelial macrophages, although whether they are taken up directly from the bronchial surface or whether they pass through epithelial cells first could not be determined. This evidence suggests that antigens, including respiratory pathogens, could gain access to cells of the avian immune system by transepithelial passage in BALT.

Effects of alpha-tocopherol, phenobarbital, and butylated hydroxyanisole during promotion of diethylnitrosamine-initiated rat hepatocarcinogenesis.

The promotion-suppressing ability of two antioxidants was measured to determine the role of oxidative stress in hepatocarcinogenesis. Four-day-old female F344/N rats were dosed with diethylnitrosamine (10 mg/kg). After weaning, they were fed semipurified diets with and without 500 ppm alpha-tocopherol, or the same two diets containing 500 ppm phenobarbital, or 5,000 ppm butylated hydroxyanisole (BHA) for 3 or 11 months. By 11 months, phenobarbital-fed groups had eaten 30% more than other groups did (p less than 0.05), suggesting a role for increased caloric intake in phenobarbital promotion. Phenobarbital and BHA significantly reduced body weights and increased liver weights compared with control rats. After three months, alpha-tocopherol significantly suppressed mean volume of placental glutathione S-transferase (PGST)-positive altered hepatic foci (AHF), regardless of xenobiotic treatment. Phenobarbital increased and BHA decreased the numbers of AHF compared with those of the control group. After 11 months, mean focal volume was significantly suppressed by BHA compared with that of the control group, and phenobarbital increased the total volume of AHF [PGST-positive plus gamma-glutamyltransferase (GGT)-positive AHF] compared with rats fed either control or BHA diets. BHA treatment also increased hepatic glutathione levels by 40% compared with control and rats fed phenobarbital. In conclusion, alpha-tocopherol had only a slight, early effect to suppress promotion of hepatocarcinogenesis. BHA suppressed some indices of promotion at both times and increased hepatic glutathione; however, BHA's toxicity (which suppressed body weight) may also be a factor in its supposable promotion-inhibitory effects.

Pemphigus foliaceus in two Shetland sheepdog littermates.

Two female Shetland Sheepdog littermates simultaneously developed pemphigus foliaceus at 6 months of age. Three other littermates were not affected. One bitch (tricolored) was not treated, and the disease has remained active for 2 years. The other bitch (blue merle) has been successfully managed with glucocorticoids and gold salts.

GM1 gangliosidosis in Portuguese water dogs: pathologic and biochemical findings.

Three Portuguese water dog siblings, all females aged 5 to 7 months, were killed following a brief period of neurologic disease. Tissues were processed for light and electron microscopy and for biochemical analyses. All pups had membranous cytoplasmic inclusions in neurons throughout the brain and spinal cord. Cytoplasmic vacuoles were present in cells of many organs outside the nervous system. GM1 ganglioside in brain was markedly elevated in all three dogs, and beta-galactosidase activity was less than 10% of control values. These findings are similar to those in GM1 gangliosidosis of man and animals although the number of organs and tissues containing vacuolated cells is greater.

Right-to-left patent ductus arteriosus with dysplastic left ventricle in a dog.

A 6-week-old Siberian Husky pup had an unusual group of congenital heart anomalies that included a right-to-left patent ductus arteriosus, a small left ventricular chamber and ascending aorta, and a dysplastic mitral valve that may have been stenotic. Anomalies were diagnosed, using cardiac catheterization, angiocardiography, and blood gas determinations. Findings were confirmed by postmortem examination.

Pulmonary clearance and lesions of lung and air sac in passively immunized and unimmunized turkeys following exposure to aerosolized Escherichia coli.

Two groups of young turkeys, one passively immunized with homologous hyperimmune serum and the other unimmunized but receiving normal turkey serum, were aerosolized with Escherichia coli. Clearance of bacteria from lung and gross and microscopic lung and air-sac lesions were determined after necropsy at timed intervals. The group mean bacterial count in lungs of passively immunized turkeys was significantly less than the mean count in unimmunized turkeys. Lung lesions were generally similar in both groups and were focused in lymphoid nodules, at the junction of primary and secondary bronchi, and at the ostia to the air sacs. Unimmunized birds developed grossly evident purulent airsacculitis by 72 hours after aerosol exposure, whereas passively immunized birds did not.

Location of the instantaneous center of joint rotation in the normal canine stifle.

Locations of 3 instantaneous centers of joint rotation (ICR) were found in the stifles of 6 healthy dogs. A novel algorithm, verified by computer simulation, was used to determine ICR from radiographs. Comparisons of ICR locations were made between flexion and extension, between left and right limbs, and between living and dead dogs, using analysis of variance. All stifles were examined for evidence of lesions, but all were normal. The normal location of the ICR in the stifle is near the joint surface, indicating that there is a predominantly rolling type of motion. As the limb flexes, the ICR moves caudally; as the limb extends, the ICR moves cranially. Significant differences in ICR position were not found between left and right limbs or between living and dead dogs. The average ICR position was significantly more caudal during extension than it was during flexion. Knowing the normal ICR position is a preliminary to diagnosing joint abnormalities, using the ICR.

Neutrophilic leukocytosis associated with metastatic fibrosarcoma in a dog.

A 3 1/2-year-old dog with extensive tumor metastases to the lungs was found to have neutrophilic leukocytosis termed a leukemoid reaction. The term leukemoid reaction describes an absolute increase in the blood leukocyte concentration without regard to a predominant cell type or to the degree of cell immaturity. These types of reactions are extremely difficult to differentiate from leukemia. Leukemoid reactions can be acute or chronic and they may have an infectious, inflammatory, toxic, or neoplastic origin. Those reactions attributable to neoplasia have been documented in medical literature, but the mechanism causing the granulocytosis has not always been clearly understood. A granulopoietin capable of stimulating a leukemoid reaction may be elaborated by certain types of tumors, tumors with extensive metastasis, or tumors involving the lungs, liver, or stomach.