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Biomedical subjects

W L Spangler

Publications and source records attributed to W L Spangler.

At least 19 recordsLinked to original sources

The histologic and epidemiologic bases for prognostic considerations in canine melanocytic neoplasia.

The laboratory records from 384 dogs with a diagnosis of either melanoma or melanocytoma were selected for study. Significant negative determinants of patient survival for melanocytic tumors were: 1) metastasis, 2) mitotic index (MI), 3) nuclear atypia, 4) tumor score, 5) increasing size/volume, 6) the presence of deep inflammation, and/or 7) intralesional necrosis. In addition to these attributes, age was a significant determinant for tumors of the skin. For the feet and lips, 8) age and 9) junction activity negatively impacted survival. Mathematic models were constructed based on these significant determinants to predict the postsurgical outcome of melanocytic neoplasia. Melanocytic oral neoplasms comprised 19% (73/384) of the neoplasms; 92% of these were classified as malignant in the biopsy report, but malignant behavior (i.e., metastasis or recurrence) was observed in only 59% of cases. The prognostic model for oral tumors based on nuclear atypia provided the most accurate (89%) prediction of overall behavior. Melanocytic tumors of the feet and lips were also 19% (73/384) of the total population. Seventy-four percent were reported malignant, whereas only 38% actually demonstrated malignant behavior. The prognostic models based on both MI or nuclear atypia had an overall correct behavioral classification of 81%. Melanocytic tumors in the skin comprised 59% (227/384) of study specimens. Although 39% were reported as malignant, only 12% exhibited malignant behavior. A satisfactory predictive model that employed MI could not be constructed, but one using nuclear atypia gave an overall correct classification in 93.3% of the cases.

Animals↗

Splenic myeloid metaplasia, histiocytosis, and hypersplenism in the dog (65 cases).

Splenectomy specimens from 65 dogs with severe, diffuse, sustained, and progressive splenomegaly were examined. The clinical signs, hematology, and serum chemistry values in for the dogs were not useful diagnostic features. Microscopic changes in the spleens were distinctive and consisted of 1) myeloid metaplasia, 2) histiocytosis, 3) erythrophagocytosis, and 4) thrombosis with segmental infarction. Ultrastructural features suggested proliferative changes in the splenic reticular cells and macrophages (reticular meshwork) that described a continuum from reactive changes associated with immunologic damage of erythrocytes to neoplastic proliferation of histiocytic components. Thirty percent of the dogs survived 12 months. Approximately one half (53%) of the dogs with complete postmortem evaluations showed multiorgan involvement with a tissue distribution and cell morphology consistent with histiocytic neoplasia. For the remaining dogs (47%), only splenic pathology was consistently present, and a specific cause of death was often not evident. Distinctive histologic changes in the splenic tissues-including mitotic activity, erythrophagocytosis, giant cell formation, thrombosis/ infarction, and the proportion and distribution of histiocytic and hematopoietic cells-were statistically evaluated for prognostic relevance. The presence of giant cells was the only reliable prognostic feature, and that was indicative of a fatal outcome. These descriptive changes of myeloid metaplasia in the canine spleen are compared with the human clinical and pathologic syndromes of 1) agnogenic myeloid metaplasia, 2) hemophagocytic syndromes, and 3) hypersplenism. These diseases in humans produce histopathologic changes in the spleen that are similar to those observed in the canine splenic tissue we examined in this study.

Animals↗

Pathologic and prognostic characteristics of splenomegaly in dogs due to fibrohistiocytic nodules: 98 cases.

Ninety-eight canine splenectomy specimens consisting of combined nodular lymphoid and fibrohistiocytic cell proliferation were evaluated for seven light microscopic characteristics. Electron microscopic features in eight primary and two metastatic nodules (liver) were also evaluated. Nodular fibrohistiocytic proliferation in the canine spleen is characterized by a mixed population of histiocytoid and/or spindle cells in varying proportions intermixed with hematopoietic elements, plasma cells, and/or lymphocytes. These nodules seem to form a continuum between splenic lymphoid nodular hyperplasia and malignant splenic stromal neoplasms (malignant fibrous histiocytoma). Immunohistochemical methods used on 32/98 specimens showed uniform and strong positive staining among fibrohisiocytic cells for vimentin and desmin; S100 protein was similarly stained in general abundance. Individual cells strongly stained with smooth muscle actin were sparse but widely distributed. Proliferating cell nuclear antigen was not useful in the subjective differentiation of nodules taken from dogs that died of spleen-related causes and those surviving 12 months following splenectomy. A spectrum of cell types were observed by electron microscopy within each nodule. Fibroblasts, macrophages, intermediate fibrohistiocytic types, and several forms of splenic reticular cells were present. There were no consistent alterations in hematology or serum chemistry profiles of these dogs to provide useful diagnostic/prognostic information. Among the 93/98 dogs with complete (12 month) follow-up information, 48% (45/93) were alive and 52% (48/93) were dead. Dogs that died or were euthanatized during the follow-up period had a median survival of 5 and 5.5 months, respectively (range 0-15 months). Forty-four percent (21/48) died from causes linked to their splenic disease, and 35% (17/48) died from competing causes. The cause of death in 21% (10/48) was unknown. Lymphoid:fibrohistiocytic proportion and mitotic index in the nodules were anatomic features most predictive of postplenectomy mortality. A higher proportion of lymphoid to fibrohistiocytic type cells was associated with increased long-term survival, whereas lower lymphoid:fibrohistiocytic proportions and higher mitotic index indicated a probability of higher short-term mortality.

Animals↗

Primary mesenchymal (nonangiomatous/nonlymphomatous) neoplasms occurring in the canine spleen: anatomic classification, immunohistochemistry, and mitotic activity correlated with patient survival.

Surgical submissions from canine splenectomy cases spanning a 3-year period (1988-1990) were evaluated. Eighty seven neoplasms of the spleen considered to be of nonangiomatous and nonlymphomatous origin were selected for morphologic classification, mitotic index determination, immunohistochemical analysis, and patient survival determination. In 76/87 cases, patient survival information was available, and the mitotic index was determined in 83/87 cases. Immunohistochemistry for selected antigens (vimentin, desmin, smooth muscle actin, myosin, and factor VIII-related antigen) was performed in 58/87 of the cases. Morphologic classification of these lesions in standard HE preparations yielded the following neoplastic groups: fibrosarcoma (19/87), undifferentiated sarcoma (19/87), leiomyosarcoma (14/87), osteosarcoma (8/87), mesenchymoma (7/87), myxosarcoma (6/87), histiocytic sarcoma (6/87), leiomyoma (3/87), lipoma-myelolipoma (2/87), liposarcoma (2/87), and malignant fibrous histiocytoma (1/87). A lack of distinct morphologic characteristics among many of the neoplasms that were classified as either fibrosarcoma, leiomyosarcoma, or undifferentiated sarcoma contrasted these groups with the relatively unambiguous features that distinguished the other sarcoma groups. Using immunohistochemical staining for muscle-specific antigens (desmin, smooth muscle actin, and myosin), specific staining often overlapped extensively within the neoplastic groups of fibrosarcomas, leiomyosarcomas, and undifferentiated sarcomas, suggesting either ambiguous morphologic findings or the possibility of a common histogenesis from smooth muscle trabeculae or a distinct population of splenic myofibroblasts. The biological behavior of all tumors examined could be placed into three categories of patient survival: (1) benign, noninvasive tumors (leiomyoma, lipoma) with prolonged survival intervals; (2) malignant tumors (fibrosarcoma, undifferentiated sarcoma, leiomyosarcoma, osteosarcoma, myxosarcoma, histiocytic sarcoma, and liposarcoma), showing severely truncated survival (median 4 months with 80-100% mortality after 12 months; and (3) intermediate survival periods (median 12 months with 50% 1 year survival) attributed to a single group of neoplasm, the mesenchymomas. The biological behavior of primary splenic nonangiomatous, nonlymphomatous sarcomas was most closely correlated with observed mitotic index. Splenic neoplasms of this type with a mitotic index < 9 showed significantly (P < 0.0001) longer survival intervals than those with an index > 9. With the exception of osteosarcoma, all anatomically defined tumor groups contained one or more specimens with a mitotic index < 9. The clinical prognosis given for splenic sarcomas should be modified according to the mitotic index as a predictive value for patient survival.

Animals↗

Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats.

Within the past 2 years, a putative causal relationship has been reported between vaccination against rabies and the development of fibrosarcomas at injection sites in cats. A retrospective study was undertaken, involving 345 cats with fibrosarcomas diagnosed between January 1991 and May 1992, to assess the causal hypothesis. Cats with fibrosarcomas developing at body locations where vaccines are typically administered (n = 185) were compared with controls (n = 160) having fibrosarcomas at locations not typically used for vaccination. In cats receiving FeLV vaccination within 2 years of tumorigenesis, the time between vaccination and tumor development was significantly (P = 0.005) shorter for tumors developing at sites where vaccines are typically administered than for tumors at other sites. Univariate analysis, adjusted for age, revealed associations between FeLV vaccination (odds ratio [OR] = 2.82; 95% confidence interval [CI] = 1.54 to 5.15), rabies vaccination at the cervical/interscapular region (OR = 2.09; 95% CI = 1.01 to 4.31), and rabies vaccination at the femoral region (OR = 1.83; 95% CI = 0.65 to 5.10) with fibrosarcoma development at the vaccination site within 1 year of vaccination. Multivariate analysis, adjusted for age and other vaccines, also revealed increased risks after FeLV (OR = 5.49; 95% CI = 1.98 to 15.24) and rabies (OR = 1.99; 95% CI = 0.72 to 5.54) vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Prevalence and type of splenic diseases in cats: 455 cases (1985-1991).

Retrospective data on the type and prevalence of splenic disease in cats were evaluated in a large number of feline splenic tissues (n = 455) submitted as surgical and necropsy specimens from private veterinary hospitals in California during a period of approximately 5.5 years. Primary and metastatic neoplasia accounted for 37% of all feline splenic lesions. Mastocytoma, lymphosarcoma, myeloproliferative disease, and hemangiosarcoma, in that order, accounted for the bulk of neoplasia. Submission of accessory splenic tissue from either the omentum or pancreas accounted for 4% (17/455), whereas hyperplastic nodules, hematomas, and the combination of these changes in the spleen accounted for 4% (19/455). Splenitis was found in 2% (8/455) of submissions. Thromboembolism with regional splenic infarction accounted for 1% (4/455) of splenic lesions in cats. The remaining splenic lesions each accounted for less than 1% of total splenic submissions, and as such, were considered incidental and of questionable clinical importance.

Animals↗

Prevalence, type, and importance of splenic diseases in dogs: 1,480 cases (1985-1989).

The prevalence data of splenic diseases from 3 sources were studied. Group 1 consisted of a general diagnostic survey of accessions submitted from private veterinary hospitals in California during a period of approximately 4 years and included 1,372 submissions of canine splenic tissue. Group 2 consisted of surgical splenectomy specimens from 92 dogs; the specimens were submitted to the laboratory for gross and histologic evaluation prior to fixation, and a questionnaire was subsequently sent to determine the outcome of the disease. Group 3 was made up of specimens of 105 splenic lesions derived from a large colony of Beagles with complete medical records and records of pathologic findings. In this study, splenic hematoma and hyperplastic nodule, not hemangiosarcoma, made up the bulk of splenic lesions. Hemangiosarcoma was the most frequent neoplasm of the canine spleen, but the combined prevalence of all other splenic neoplasms was similar to that of hemangiosarcoma alone. Splenic hematoma and hemangiosarcoma were grossly indistinguishable in most cases. Hyperplastic lymphoid nodules and hematomas of the spleen appeared to represent a continuum. If that finding was correlated with microscopic splenic blood flow, specific causal relationship could be suggested. Prognostically, the live/dead ratio and mean survival of dogs with various splenic lesions differed significantly.

Age Factors↗

A retrospective clinicopathologic study of 212 dogs with cutaneous hemangiomas and hemangiosarcomas.

The relationship between skin pigmentation and piliation and the development of hemangiomas and hemangiosarcomas in the dermis and subcutaneous tissue was studied in 212 dogs. These 212 dogs had a combined total of 306 tumors; 38 of these 212 dogs had two or more of the same tumor in a different location or a combination of hemangioma and hemangiosarcoma. The average age of the dogs at the time of excision of these tumors was greater than 10 years. There was no sex predilection for the presence or absence of tumors. Cutaneous hemangiomas (73%) were more common than cutaneous hemangiosarcomas (27%). Hemangiomas had no predilection for dermis (51%) or subcutaneous tissue (47%), but hemangiosarcomas had a marked predilection for dermis (73%) over subcutaneous tissue (7%). Dogs with short hair coats and lightly pigmented skin had more hemangiomas and hemangiosarcomas of the dermis (65%) than did dogs with variable length hair coats and pigmentation (28%). Dogs with short hair coats and lightly pigmented skin had fewer hemangiomas and hemangiosarcomas of the subcutaneous tissue (10%) than did dogs with variable length hair coats and pigmentation (22%). Dogs with short hair coats and lightly pigmented skin also had more hemangiomas and hemangiosarcomas of ventral glabrous skin (65%) than did dogs with variable length hair coats and pigmentation (22%). In addition, there was no predilection of subcutaneous hemangiosarcoma for haired (33%) versus glabrous (33%) skin, but dermal hemangiosarcoma had a marked predilection for the glabrous skin (63%) when compared with haired skin (10%). The increased incidence of dermal hemangiomas and hemangiosarcomas in ventral glabrous skin suggests an association between solar radiation and the biologic properties of glabrous skin in the genesis of these tumors.

Age Factors↗

Salivary gland disease in dogs and cats: 245 cases (1985-1988).

Diagnostic pathology records spanning 41 months (July 1985 through November 1988) were searched for diagnoses of salivary gland disease in dogs and cats. Review of 87,392 records from that period revealed 245 cases (0.3%) in which salivary gland tissue had been evaluated. During that period, salivary gland tissue was submitted to the laboratory almost twice as often from dogs (160 cases) as from cats (85 cases). On the basis of histologic examination, 89% of salivary gland submissions from small animal practices were allotted to 1 of 5 major categories: malignant neoplasms (30%; 74/245), sialadenitis (26%; 64/245), normal salivary gland (16%; 40/245), sialocele (9%; 21/245), and salivary gland infarction (8%; 20/245). The remaining 11% of submissions included various degenerative or fibrotic lesions, ductal ectasia, sialolithiasis, edema, benign neoplasia, and secondary salivary involvement with systemic or cervical lymphosarcoma or with fibrosarcoma in the head and neck.

Animals↗

Pancreatic response in rats and mice to trypsin inhibitors from soy and potato after short- and long-term dietary exposure.

The effects on the pancreas of chronic (95 wk) dietary exposure to protease inhibitors from soy and potato were compared in rats and mice. Soy and potato trypsin inhibitor (TI) concentrates were prepared from defatted raw soy flour and potato juice, respectively, by selective precipitation and ultrafiltration. Animals were fed a diet in which casein supplied approximately 20% protein. Each concentrate (less than 1% of the diet) was added to provide 100 and 200 mg of trypsin inhibitor activity per 100 g of diet. In short-term (28 d) experiments in rats, both sources of TI decreased the apparent nutritional quality of casein and produced pancreatic hypertrophy consistent with a hormonally mediated feedback mechanism for pancreatic adaptation to diet that is interactive with the nutritional status of the animal. After long-term feeding (95 wk), soy and potato TI produced dose-related pancreatic pathology in rats consisting of nodular hyperplasia and acinar adenoma, which was typical of that associated with raw soy flour. Although mice responded similarly to rats to soy TI in short-term (28-d) feeding experiments, they were resistant to the formation of these lesions following long-term feeding. This considerable species variation in propensity to develop preneoplastic and neoplastic lesions of the pancreas is not predicted by the short-term hypertrophic and hyperplastic response of the pancreas to TI.

Adenoma↗

Safety of trypsin inhibitors in the diet: effects on the rat pancreas of long-term feeding of soy flour and soy protein isolate.

The effects on the pancreas of chronic dietary exposure to defatted soy flour and soy protein isolate have been studied in two two-year feeding trials in rats. Emphasis was placed on detecting changes that might accompany low levels of dietary trypsin inhibitor (TI) as might be found in edible grade soy products and on studying the influence of protein nutrition. The major pathological findings in the pancreas were nodular hyperplasia (NH), consisting of foci of hyperplastic acinar cells often grossly visible by six months, and the benign neoplastic lesion, acinar adenoma (AA), which developed more slowly. In the first feeding trial, the objectives were to obtain the dose-response relationship of pancreatic pathology to dietary TI provided by raw and heated soy flour and to study the nutritional interaction of protein level which was varied from 10% to 30% using casein supplementation. Also, the responses to raw and heated soy protein isolate were compared to determine whether the removal of more than 50% of the constituents found in soy flour would alter the development of pancreatic lesions. In the second trial, the effect of unusually low levels of TI in raw and heat-treated soy protein isolate, prepared through a salt extraction process and fed at 10% and 30% protein in the diet, was investigated. The incidence of both NH and AA was positively related to the TI content of the diet. The probit transformation of the percent incidence of AA was linearly related to the log of TI/g protein in the diet. A single curve best described the response to 20% and 30% protein, with a slope that was distinctly greater than that for 10% protein. The intersection of the two curves near the TI concentration of edible grade soy flour predicts that protein level in the diet can be expected to have essentially no effect on the incidence of AA when TI activity is in this range. But, for proteins containing greater concentrations of TI, increasing the level of protein in the diet will increase the incidence of pancreatic pathology, while for proteins with quite low levels of TI, increasing the protein in the diet above 10% will have a protective effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of paraquat on plasma glucose, cortisol, catecholamines, and insulin in the beagle.

Paraquat is known to produce hyperglycemia in rodents, although the mechanisms responsible for the hyperglycemic effect of paraquat are not clearly understood. In this study we report the effects of paraquat (25 mg/kg iv) on plasma glucose, cortisol, catecholamines, and insulin in dogs. Paraquat caused a significant increase in plasma glucose level at all times of measurement except at 0.5 hr following paraquat administration. The cortisol levels after paraquat treatment were increased to 133, 305, 279, 418, 517, 672, and 567% above zero time control at 0.5, 1.5, 3, 6, 12, and 24 hr, and at death time respectively. The catecholamines at these times were increased to 42, 17, 72, 118, 138, 226, and 435% above the control. In contrast to cortisol and catecholamines, the plasma insulin levels after paraquat treatment were significantly decreased at 3, 6, 12, and 24 hr. These hormonal observations can explain, at least in part, the observed hyperglycemia, since all promote hyperglycemic states. For example, cortisol is gluconeogenic, catecholamines are glycogenolytic, and lower insulin levels result in depressed peripheral glucose utilization.

Animals↗

A morphologic study of two types of porcine valve bioprostheses: comparison of aortic wall thickness.

Outer aortic wall morphology and thickness were compared in the Hancock porcine aortic bioprosthesis and the Carpentier-Edwards porcine aortic bioprosthesis. The overall average aortic wall thickness, the average maximum thickness, the average minimum thickness, and the average variation in aortic wall thickness were greater in the Hancock valve. Differences in preparation technique accounted for the disparities. The tunica adventitia and variable amounts of the outer tunica media were generally removed during processing of the Carpentier-Edwards valve prior to mounting in the stent. The removal of this tissue at times exposed to deeper collagenous cusp anchor at the commissures. Possible implications of these differences are briefly considered.

Animals↗

Oval lipid corneal opacities in beagles.

Naturally occurring, oval opacities at the junction of the middle and inferior thirds of the cornea were found in an experimental beagle dog colony and were examined by light and electron microscopy. Abnormalities were limited to the anterior stroma and consisted of extracellular rhomboid crystalline spaces. Spherical or elliptical vacuolar spaces, sometimes containing electron-dense amorphous debris, distorted stromal lamellae. Stromal keratocytes in affected areas revealed a range of changes from hyperplasia of organelles to degeneration and necrosis.

Animals↗