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Biomedical subjects

Douglas J. Weiss

Publications and source records attributed to Douglas J. Weiss.

15 recordsLinked to original sources

Cytologic evaluation of benign and malignant hemophagocytic disorders in canine bone marrow.

Canine hemophagocytic disorders were studied to better understand the cytologic features that differentiate benign and malignant disease. Of 286 canine clinical bone marrow reports evaluated retrospectively, 13 (4.5%) noted at least 3% hemophagocytic macrophages. Macrophages comprised between 6% and 44% of nucleated bone marrow cells. Clinical diagnoses for dogs with hemophagocytic disorders included malignant histiocytosis (n = 2), myelodysplastic syndromes (n = 4), round cell neoplasia (n = 2), immune-mediated disorders (n = 2), and idiopathic hemophagocytic syndrome (n = 3). Differentiation of benign and malignant forms of histiocytosis was problematic. Two dogs with a diagnosis of hemophagocytic syndrome had macrophages with atypical features similar to those described for malignant histiocytosis. Furthermore, only 2 of 11 dogs with presumably benign hemophagocytic disorders had exclusively mature macrophages in bone marrow. Other dogs had variable numbers of large reticular-type cells characterized by lacy chromatin, anisocytosis, anisokaryosis, and prominent and/or multiple nucleoli. On the basis of these results, cytomorphologic evaluation of bone marrow alone may not be adequate to consistently differentiate benign and malignant forms of hemophagocytic disorders.

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Cytologic evaluation of primary and secondary myelodysplastic syndromes in the dog.

Myelodysplastic syndromes are a heterogeneous group of acquired primary and secondary alterations of hematopoietic stem cells that result in cytopenias in blood and cytologic features of dysplasia in blood and/or bone marrow. To better understand the cytologic features that would permit differentiation of primary and secondary forms of myelodysplasia, we reviewed 267 consecutive bone marrow reports from dogs. These reports indicated that 34 dogs (12.7%) had dysgranulopoiesis, dyserythropoiesis, and/or dysthrombopoiesis in >10% of granulopoietic cells, erythroid cells, and/or megakaryocytes, respectively. Thirteen dogs had primary myelodysplastic syndromes, and 21 had secondary myelodysplastic syndromes. Of the 13 dogs with primary myelodysplasia, 4 were subclassified as myelodysplastic syndrome with refractory anemia (MDS-RA), and 9 were subclassified as myelodysplastic syndrome with excess blasts (MDS-EB). Secondary conditions associated with dysplasia in the bone marrow included malignant lymphoma (n = 5), myelofibrosis (n = 3), immune-mediated thrombocytopenia (n = 4), immune-mediated hemolytic anemia (n = 5), multiple myeloma with melphalan administration (n = 1), pyometra with estrogen administration (n = 1), polycythemia vera (n = 1), and thrombopathia (n = 1). MDS-RA was characterized by <5% myeloblasts in bone marrow, normal granulocyte maturation ratio, increased erythroid maturation ratio, and dysplastic changes in >15% of erythroid cells. MSD-EB was characterized by >/=5% myeloblasts in bone marrow, high granulocyte maturation and erythroid maturation ratios, >/=32% dysplastic granulocytes, and the presence of small atypical immature myeloid cells. Secondary myelodysplastic syndromes were characterized by <5% myeloblasts in bone marrow, variable granulocyte maturation and erythroid maturation ratios, and variable dysplastic features. These results indicate that morphology alone cannot be used to distinguish primary and secondary myelodysplastic syndromes in dogs.

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Cytologic evaluation of inflammation in canine liver aspirates.

Liver aspiration cytology has been used routinely for more than a decade for the evaluation of canine and feline liver disease. However, the value of liver cytology in detecting inflammatory liver disease is poorly defined. We retrospectively reviewed 51 canine liver cytology reports and compared the conclusions with those from concurrent surgical biopsy reports. Overall sensitivity of cytology for diagnosis of inflammatory liver disease was 93% and specificity was 96%. For suppurative hepatitis (n = 14), the sensitivity of cytologic diagnosis was 100% and the specificity was 95%. For chronic active hepatitis (n = 13), the sensitivity of cytologic diagnosis was 100% and the specificity was 93%. For lymphocytic hepatitis (n = 3), the sensitivity of cytologic diagnosis was 33% and the specificity was 100%. We conclude that canine liver aspiration cytology is a highly sensitive test for the detection of suppurative and chronic active inflammation; however, it is insensitive for the detection of lymphocytic hepatitis.

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Flow cytometric evaluation of canine bone marrow differential cell counts.

Three flow cytometric techniques were evaluated for determination of differential cell counts on canine clinical bone marrow specimens. Techniques included staining bone marrow specimens with 2'7'-dichlorofluorescein (DCF) or 3,3'-dihexyloxacarbocyanine iodide (DiOC6) and evaluation of forward-angle light scatter vs. side-angle light scatter plots. Flow cytometric evaluation of bone marrow cells stained with DCF failed to separate bone marrow cells into distinct cell populations. Staining with DiOC6 resulted in separation of bone marrow cells into populations of mature and immature erythroid cells, mature and immature myeloid cells, and lymphocytes. The scatter plot method resulted in identification of mature and immature erythroid cells, immature myeloid cells, metamyelocytes, and bands and segmenters. Lymphocytes could not be differentiated from mature erythroid cells by the scatter plot method. When the results of the DiOC6 method and the scatter plot method were compared with manual bone marrow differential cell counts, the scatter plot method had more similar mean values and higher correlation coefficients. The scatter plot method has the potential of providing rapid semiquantitative assessment of bone marrow differential cell counts in dogs for specimens that contain low numbers of lymphocytes.

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Myelodysplastic syndrome with sideroblastic differentiation in a dog.

A dog with myelodysplastic syndrome had microcytic hypochromic anemia, with siderocytes, poikilocytosis, hypersegmented neutrophils and giant platelets in peripheral blood. In bone marrow, the erythroid series showed immaturity, asynchronous maturation and sideroblasts. Dysgranulopoiesis and dysthrombopoiesis also were present, and hemosiderin was increased. Serum iron concentration was high, and both iron deficiency and lead toxicity were excluded as the cause of dyscrasia. This case represents a unique variant of myelodysplastic syndrome, best described as sideroblastic myelodysplasia. We propose the terms dyserythropoiesis, sideroblastic dyserythropoiesis, dyserythropoiesis with excess blasts, myelodysplasia and sideroblastic myelodysplasia to describe and categorize myelodysplastic syndromes in dogs.

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A retrospective study of canine pancytopenia.

To better define the incidence and causes of canine pancytopenia, we retrospectively evaluated the results of complete blood counts submitted to the University of Minnesota Veterinary Teaching Hospital during a 1-year period. Pancytopenia was defined as packed cell volume < 36%, total leukocyte count < 6,000/microliter or total segmented neutrophil count < 3,000/microliter, and platelet count < 200,000/microliter. Of 4,560 complete blood counts, 110 (2.4%) samples from 51 dogs met the criteria for pancytopenia. Eleven different disease processes were identified. These included chemotherapy-associated pancytopenia (n=22), parvovirus infection (n=5), malignant histiocytosis (n=5), idiopathic aplastic anemia (n=3), sepsis (n=3), myelodysplastic syndrome (n=3), immune-mediated hematologic disease (n=3), lymphoblastic leukemia (n=2), ehrlichiosis (n=2), estrogen toxicity (n=2), and multiple myeloma (n=1). Malignant histiocytosis and idiopathic aplastic anemia occurred more frequently than was expected. Doxoruicin was the chemotherapeutic agent associated with pancytopenia. Hematologic recovery and patient survival time varied with the cause of pancytopenia; therefore, a specific diagnosis was essential for establishing prognosis. Differentiation among causes of pancytopenia requires a systemic approach that includes elimination of infectious and drug-induced causes, and examination of bone marrow aspiration and core biopsy specimens.

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Expression of tissue factor in experimental bovine pneumonic pasteurellosis and endotoxemia.

Tissue factor (TF), a cell surface-associated cofactor and activator of coagulation factor VII, has been implicated in the local and systemic activation of coagulation associated with sepsis. This study describes the pattern of TF expression in experimental bovine pneumonic pasteurellosis and endotoxemia. Immunohistochemical techniques were used to localize TF antigen in tissue sections. Tissue factor expression was not observed in tissues from control animals. In response to Pasteurella haemolytica challenge, TF was expressed within alveolar walls, by mononuclear inflammatory cells within alveoli, and in walls of arteries, arterioles, bronchi, and bronchioles. Tissue factor was not detected in unaffected lung, liver, spleen, lymph node or kidney tissue. Administration of Escherichia coli endotoxin intravenously resulted in tissue factor expression in lung, spleen, and lymph node tissue. Results of this study indicate that TF is expressed locally at sites of inflammation and systemically in endotoxemia. Therefore, TF may be involved in coagulation events associated with pneumonic pasteurellosis.

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Characterization of portal lymphocytic infiltrates in feline liver.

To better understand the relationship of portal lymphocytic infiltrates to feline inflammatory liver disease, liver sections were semiquantitatively evaluated from healthy cat and liver sections randomly selected at necropsy from clinical cases. Healthy specific pathogen-free kittens and healthy young adult cats had up to 10 lymphocytes and plasma cells per portal area. Neutrophils were infrequently seen in portal areas. Approximately one-third of sections obtained from clinical cases younger than 10 years had increased numbers of lymphocytes and plasma cells in portal areas. Seventy percent of these had a concurrent increase in neutrophils. Eighty-two percent of liver sections obtained from clinical cases older than 10 years had increased numbers of portal lymphocytes and plasma cells. Almost all of these sections had concurrent fibrosis and bile duct proliferation. These data indicate that a progressive lymphocytic portal hepatitis is a common finding in cats older than 10 years.

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Qualitative evaluation of irregularly spiculated red blood cells in the dog.

Irregularly speculated red blood cells (IS-RBC) were quantified on fresh blood fixed in glutaraldehyde and were compared to RBC shape changes observed on Wright's-stained blood smears, RBC histograms, and RBC distribution widths (RDW). IS-RBC were infrequently found in healthy control dogs. Twenty dogs with increased IS-RBC were evaluated. The most common clinical diagnoses were lymphosarcoma (seven cases), glomerulonephritis (two cases), hemangiosarcoma (two cases), and chronic liver disease (two cases). Five cases had evidence of disseminated intravascular coagulopathy. In 12 of the 20 cases, keratocytes, schizocytes, and/or acanthocytes were detected in the monolayer area of blood smears. In the other seven cases, keratocytes, schizocytes, and/or acanthocytes were found only in thick areas of the smears. Acanthocytes were the most frequent cell type seen, while schizocytes were absent or present only in low numbers. RBC histograms had a shoulder on the left side of the tracing in six of the 20 cases, suggesting the presence of RBC fragments; however, cases with evidence of platelet aggregation had similar shoulders in RBC histograms. Red cell distribution widths were increased in 12 of the 20 cases with IS-RBC; however, the increase in RDW did not correlate with the presence of schizocytes and was most likely the result of reticulocytosis. This study suggests that quantitative evaluation of RBC shape is a more sensitive method for detection of mild RBC fragmentation when compared to blood smear evaluation, RBC histograms, or RDW. Additionally, acanthocyte-type cells were the most frequent shape change seen in dogs with evidence of RBC fragmentation.

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Inflammatory disorders of bone marro.

Inflammatory lesions in bone marrow, observed during a 2 year period at the College of Veterinary Medicine, University of Minnesota, were reviewed. Of 24 bone marrow specimens with evidence of inflammation, six were classified as acute inflammation, nine as fibrinous inflammation, five as chronic inflammation/hyperplasia, three as granulomatous inflammation and one as nodular lymphoid hyperplasia. Acute inflammation commonly accompanied bacterial sepsis. Two patterns of acute inflammation were identified. One pattern consisted of multifocal microabscesses. The other pattern of acute inflammation consisted of perivascular infiltrates of neutrophils, fibrin, edema, and hemorrhage. The most common disorder associated with fibrinous inflammation was disseminated intravascular coagulopathy. Chronic inflammation was difficult to differentiate from chronic immune stimulation. Discrete granulomas were identified in the marrow of animals with systemic mycotic disease, idiopathic systemic granulomatous disease, and serous atrophy of fat. This study indicates that a broad variety of inflammatory disorders occur in animal bone marrow and that these disorders can be classified based on general categories of inflammation described in other tissues.

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Spurious hyperphosphatemia in a dog with chronic lymphocytic leukemia and an IgM monoclonal gammopathy.

Spurious hyperphosphatemia was diagnosed in a 6-year-old, neutered female, mixed-breed dog with chronic lymphocytic leukemia associated with an IgM monoclonal gammopathy. The spurious hyperphosphatemia was probably caused by paraprotein precipitation which interfered with the ASTRA 8 automated analyzer measurements. Serial dilutions of the sample did not change the phosphorus value. Another analyzer system in which a protein-free sample was prepared prior to analysis gave a normal serum phosphorus concentration. There was a linear relationship between the amount of paraprotein and the measured total serum inorganic phosphate (r=0.75). A review of 700 chemistry profiles from dogs and cats and a review of 36 cases with polygonal gammopathy and 6 cases with monoclonal gammopathy did not reveal other cases of spurious hyperphosphatemia.

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Platelet function in the racing thoroughbred: implication for exercise-induced pulmonary hemorrhage.

Platelet function was evaluated in horses with exercise-induced pulmonary hemorrhage (bleeder) and in control horses (nonbleeder). Platelet aggregation, secretion, and adhesion to rabbit aortic subendothelium were similar for bleeders and nonbleeders. Platelets readily aggregated in response to ADP, thrombin, collagen, and arachidonic acid, but platelet secretion occurred only with high concentrations of thrombin. Platelets readily adhered to rabbit aortic subendothelium and tended to form large thrombi rather than platelet monolayers or aggregates. These data suggest that horses may be predisposed to thrombus formation and subsequent microvascular obstruction.

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Quantitative evaluation of echinocytes in the dog.

Echinocytes were evaluated quantitatively in both healthy and sick dogs and compared with red blood cell (RBC) morphology on Wright's-stained blood smears. Of 68 samples submitted from sick dogs, 32 had high echinocyte numbers. Two diseases, glomerulonephritis and lymphosarcoma, accounted for 15 of the 32 cases. In only four instances were echinocytes reported from blood smear evaluation and not found to be high by quantitative studies. We conclude that nonartifactual echinocytosis occurs in the dog and that it may be associated with specific diseases.

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