Presumptive fenbendazole toxicosis in North American porcupines

CASE DESCRIPTION: 4 North American porcupines were evaluated because of diarrhea or neutropenia (or both) that developed after treatment with fenbendazole for intestinal parasites. CLINICAL FINDINGS: Complete blood cell count abnormalities included severe neutropenia in all affected porcupines and mild anemia in some of them. In 2 porcupines, postmortem findings included bone marrow hypoplasia and intestinal crypt cell necrosis. TREATMENT AND OUTCOME: Affected porcupines received supportive care including fluid supplementation and broad-spectrum antimicrobials. The 2 surviving animals recovered after 9 to 33 days of treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Fenbendazole is an anthelminthic that may be used in an extralabel manner for the treatment of intestinal parasitism in wildlife species. The drug inhibits mitosis and can affect rapidly dividing cell lines, such as those in the bone marrow and intestinal crypt mucosa. Fenbendazole may not be an appropriate anthelminthic choice in North American porcupines.     

Bone marrow hypoplasia associated with fenbendazole administration in a dog

A 1.5-year-old Doberman pinscher was presented with sudden-onset of fever and malaise. Twelve days prior to presentation, fenbendazole therapy was initiated for a suspected lungworm infection. Results of a complete blood count on presentation showed pancytopenia, while histopathological evaluation of a bone marrow core sample revealed bone marrow hypoplasia of undetermined etiology. Bactericidal antibiotics and fluid therapy, as well as discontinuation of fenbendazole administration, led to a complete resolution of clinical and hematological abnormalities within 15 days. An idiosyncratic reaction to fenbendazole was suspected based on the absence of infectious, neoplastic, autoimmune, and toxic etiologies, as well as resolution of clinical signs and pancytopenia upon drug withdrawal.     

Vincristine overdose in a cat: clinical management, use of calcium folinate, and pathological lesions

A 6-year-old female neutered Burmese cat received a 10 times overdose (5mg/m(2)) of vincristine, administered in error. Supportive therapy, including administration of calcium folinate, was instigated within 8h. Despite treatment, the patient exhibited deterioration in renal and respiratory function and died 72 h after overdose. Necropsy was performed within 24h of death. Gross examination revealed pulmonary oedema and a pale brown liver with a prominent lobular pattern. Histological examination revealed marked apoptosis and necrosis of the bone marrow myeloid series, and mild to moderate apoptosis and necrosis of the erythroid and megakaryocyte series. Multifocal necrosis of the renal tubules, hepatocytes, and small intestinal crypt epithelium was also observed. Use of calcium folinate as a rescue therapy following vincristine overdose in humans has been previously documented. If treatment is to be successful in cases of vincristine overdose in cats, then a more complete understanding of the pathogenesis of vincristine toxicity in companion animal species is required.     

Bone marrow hypoplasia in eight dogs with Sertoli cell tumor

Eight male dogs with Sertoli cell tumor had pancytopenia and bone marrow hypoplasia attributed to endogenous estrogen myelotoxicosis. Clinical signs were hemorrhage caused by thrombocytopenia, anemia caused by blood loss or diminished erythrocyte production, and infection and fever associated with granulocytopenia. Other signs attributed to hyperestrogenism were feminization and prostatic disease. Two dogs recovered after castration and supportive treatment, but 5 other similarly treated dogs died of hematopoietic failure. One dog was euthanatized.     

Pathological study of lead poisoning in whooper swans (Cygnus cygnus) in Japan.

During spring 1989, thirty-three whooper swans (Cygnus cygnus) died at Lake Miyajima in Hokkaido, Japan; 15 were examined. The birds were diagnosed as having subacute lead poisoning due to ingestion of spent lead shot. The main gross findings were bile-stained liver, edematous or gelatinous bone marrow, bile-stained lining with hyperkeratosis and lead pellets in the gizzard, and proventricular impaction. Histopathologically, there was lead-hemolytic jaundice of the liver, hemosiderosis in the liver and spleen, and hypoplasia of the bone marrow with increased numbers of polychromatic erythroblasts. Acid-fast intranuclear inclusion bodies were seen in kidneys of seven swans. Under electron microscopy, inclusion bodies had frayed contours and consisted of high-electron-dense fine granules. The lead concentration of the liver ranged from 5.5 to 44.3 mg/kg wet weight. It was suggested that these changes resulted from excess breakdown of erythrocytes, inhibition of heme synthesis, and impaired erythropoiesis caused by lead shot.     

Intestinal function and gut microflora of broiler chickens as influenced by cereal grains and microbial enzyme supplementation

A study was conducted to investigate the effect of the key cereal grains and a microbial enzyme supplement on broiler chicken performance, gut microflora and intestinal function. Ingestion of the barley-based diet was associated with low 28-day body weight, decreased feed intake and high FCR. The supplemental enzyme increased feed intake and weight gain of the chickens on a wheat-based diet. The pH of the gizzard and caecal contents varied with the grain type. Enzyme supplementation reduced ileal viscosity, particularly in birds that received the diet based on wheat. The birds on the barley-based diet had lower ileal digestibility of dry matter, protein and energy than those given maize and sorghum-based diets. The ileal digestibility of starch was increased by enzyme supplementation. Enzyme supplementation increased the number of total anaerobic bacteria in the gizzard of birds fed on sorghum and increased lactobacilli in the gizzard of those fed both sorghum and wheat. The birds fed the sorghum-based diet had the lowest counts of caecal total anaerobic bacteria and lactobacilli. Jejunal villus height and villus:crypt ratio of birds fed the barley-based diet were the lowest when compared with those fed the other diets. Enzyme application induced an increase in villus height and villus:crypt ratio of birds on wheat, crypt depth on barley and a reduction in crypt depth of chickens on the sorghum-based diets. The highest activity of maltase and the lowest activity of sucrase were observed in tissue from birds fed on maize and sorghum-based diets respectively. The differences in the performance of broilers on cereal grains could be explained by changes in intestinal morphology, enzyme activities and gut microflora as well as nutrient digestibility. The improved performance by supplemental enzyme in wheat-fed chickens was associated with beneficial changes in intestinal morphology and digesta viscosity.     

Bone marrow necrosis in dogs: 34 cases (1996-2004)

OBJECTIVE: To identify the incidence, potential causes, and clinical and clinicopathologic features of bone marrow necrosis in dogs. DESIGN: Retrospective study. ANIMALS: 34 client-owned dogs. PROCEDURES: Reports of cytologic examinations of bone marrow specimens performed between 1996 and 2004 were reviewed. All reports that indicated the presence of necrosis, stromal disruption, phagocytic macrophages, individual cell necrosis, or myelofibrosis were evaluated further. RESULTS: Of 609 reports of bone marrow evaluations performed during the study period, 34 (5.6%) had evidence of bone marrow necrosis. Nine dogs had no evidence of associated diseases or drug or toxin exposure, and 25 dogs had associated disease conditions or drug exposures. All 9 dogs with idiopathic bone marrow necrosis were anemic (mean Hct, 14%), but only 3 had neutropenia, and 3 had thrombocytopenia. All 9 had myelofibrosis. Of the 25 dogs with associated disease conditions or drug exposures, only 14 (56%) had anemia (mean Hct, 33%). In addition, 14 (56%) had neutropenia and 18 (72%) had thrombocytopenia. Only 10 (40%) had myelofibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that bone marrow necrosis may be common in dogs with hematologic disorders. In most dogs, bone marrow necrosis was associated with an underlying disease condition or drug exposure, but idiopathic bone marrow necrosis was also identified. Disease conditions that should increase suspicion of possible bone marrow necrosis include sepsis, lymphosarcoma, and systemic lupus erythematosus; drug exposures that should increase suspicion of possible bone marrow necrosis include chemotherapeutic agents, phenobarbital, carprofen, metronidazole, and mitotane.     

Myeloid and Megakaryocytic Hypoplasia in Related Standardbreds

Myeloid and megakaryocytic bone marrow hypoplasia in association with moderate to profound neutropenia was observed in 8 young Standardbred horses sired by the same stallion; 7 horses were intermittently thrombocytopenic. Evaluation of serial neutrophil counts in 2 horses suggested that a cyclic variation in neutrophil numbers was present, that lymphocyte numbers increased when neutrophil counts decreased, and that platelet counts decreased when neutrophil counts decreased. Preliminary bone marrow cultures indicated that myeloid progenitor cells were present and that these cells were able to respond to exogenous growth factors by differentiating. A bone marrow microenvironment or growth factor defect is suspected. Seven of 8 horses died or were euthanized. One horse with moderate neutropenia and a normal platelet count has been racing for 3 years. Necropsies in 4 horses did not reveal a cause for the myeloid hypoplasia. A familial basis for the disease is suspected.     

Characterization of a reo-like virus and its isolation from and pathogenicity for parrots

Necropsy of an African Grey parrot (Psittacus erithacus) revealed subcutaneous hemorrhages, multiple foci and microfoci of necrosis in the liver, spleen, bone marrow, and intestinal lamina propria, mild air sacculitis, and epicarditis. A virus, isolated from the liver, was non-enveloped, was polyhedral with a diameter of 84.9 +/- 3.4 nm, possessed a double-stranded RNA genome, and was stable at pH 3.0 for 30 minutes and at 56 C for up to 120 minutes. The virus was propagated in cell culture, purified by limiting dilution, and inoculated into two African Grey parrots. The experimental infections were fatal on the 8th and 9th days postinoculation in the orally and intramuscularly inoculated birds, respectively, and produced hemorrhages and necrotic lesions that recapitulated those of the index case.     

Bone marrow necrosis and myelophthisis: manifestations of T‐cell lymphoma in a horse

Abstract: A 14‐year‐old spayed American Paint mare was evaluated for mild colic, anorexia, pyrexia, and pancytopenia. Physical examination revealed mild tachycardia, tachypnea, and pale mucous membranes. Serial laboratory analyses revealed progressive pancytopenia, hyperfibrinogenemia, and hyperglobulinemia. A few large atypical cells were observed in peripheral blood smears. Results of tests for equine infectious anemia and antipenicillin antibody were negative. Serum protein electrophoresis indicated a polyclonal gammopathy. Smears of bone marrow aspirates contained hypercellular particles, but cell lines could not be identified because the cells were karyolytic, with pale basophilic smudged nuclei and lack of cellular detail. A diagnosis of bone marrow necrosis was made. Treatment consisted of antimicrobials, nonsteroidal anti‐inflammatory drugs, and corticosteroids. The pyrexia resolved; however, the pancytopenia progressively worsened and petechiation and epistaxis developed. The horse was humanely euthanized. Postmortem examination revealed a diffuse round cell neoplasm infiltrating the kidneys, spleen, lymph nodes, lungs, and bone marrow. Immunophenotyping results (CD3+, CD79α−) indicated the neoplastic cells were of T‐cell lineage. Infiltration of lymphoma cells into the bone marrow appeared to have resulted in severe myelophthisis and bone marrow necrosis. Bone marrow necrosis has been associated previously with lymphoma in humans and dogs. To our knowledge, this is the first reported case of lymphoma resulting in bone marrow necrosis in a horse.     

Blood smear from a cat: features to "dys"cover

A 4-year-old, spayed female, domestic shorthair cat was presented for lethargy, nonregenerative anemia, and inappetence. Results of a CBC included macrocytic, normochromic, nonregenerative anemia and a glucocorticoid-associated leukogram. On blood smear examination, neutrophils had abnormal features including hyposegmentation and a diffuse chromatin pattern with nuclear filament formation and nuclear blebbing. Microscopic examination of a roll preparation of bone marrow revealed hypolobulated megakaryocytes with asynchronous maturation of nuclei. The granulocytic to erythrocyte (G:E) ratio was 76. Segmented neutrophils had asynchronous maturation and dysplastic features. The entire erythroid lineage was markedly decreased for the degree of anemia and rare dysplastic features were noted in erythroid precursor cells. The interpretation of bone marrow findings was erythroid hypoplasia, megakaryocytic dysplasia, and granulocytic hyperplasia with dysplasia. Histopathologic examination of a bone marrow core sample also revealed myeloid hyperplasia and erythroid hypoplasia. The result of a direct immunofluorescence assay for FeLV performed on the bone marrow roll preparation was positive. A diagnosis of dysmyelopoiesis associated with FeLV infection was made. This case was unique in that the dysplastic changes occurred in cell lines that did not have associated cytopenias. The dysmyelopoiesis most closely resembled myelodysplastic syndrome with refractory cytopenia (MDS-RC); however, secondary dysmyelopoiesis could not be ruled out.     

Influence of Dietary Sesame Meal Level on Histological Alterations of the Intestinal Mucosa and Growth Performance of Chickens

A feeding experiment was conducted to evaluate the effects of dietary sesame meal (SM) on growth performance and histological intestinal alterations of layer chickens. Thirty-two White Leghorn male chickens were divided into 4 groups of 8 birds. They were fed 0, 10, 20, or 30% dietary SM for 28 d. After the feeding experiment, average villus height, epithelial cell area, and crypt cell mitosis numbers were morphometrically compared with an image analyzer, and the results were analyzed with Duncan's multiple range test. The morphological changes of epithelial cells on the villus apical surface were observed morphologically using scanning electron microscope. The growth performance data revealed no significant differences in birds fed up to 20% dietary SM, significantly lower values were revealed in the 30% dietary SM group. At 10% dietary SM, growth performance tended to be improved. Most values of the intestinal villus height, epithelial cell area, and crypt cell mitosis numbers were not different among groups for each intestinal segment. Flat epithelial cells were on the intestinal villus apical surface in the group fed 0% dietary SM. Those cells developed into protuberated cells in the group fed 10% dietary SM, and these protuberated cells disappeared gradually with increasing dietary SM levels. Considerations for current growth performance and histological intestinal alterations suggest that the SM would have no detrimental effect on the growth performance with up to 20% dietary SM nor on the intestinal villi with up to 30% dietary SM, but hypertrophy was observed in the epithelial cells of bird fed up to 20% dietary SM. In conclusion, up to 20% SM could be incorporated into diets fed under commercial conditions to male birds of laying strains in the developer period.     

Expression of viral proteins in feline leukemia virus-associated enteritis

Fourteen cases of feline leukemia virus (FeLV)-associated enteritis were immunohistologically examined for the expression of FeLV proteins gp70, p27, and p15E in the jejunum, mesenteric lymph nodes, spleen, and bone marrow. Results were compared with those of FeLV-infected cats without intestinal alterations. Other viral infections and specific bacterial, fungal, and parasitic infections were excluded by standard microbiologic methods, histopathology, immunohistology, and in situ hybridization. In FeLV-associated enteritis, FeLV gp70 and p15E were strongly expressed in intestinal crypt epithelial cells. In contrast, FeLV-positive cats without intestinal alterations showed only faint staining for gp70 and p15E and comparatively strong p27 expression in these cells. Findings suggest a direct relation between FeLV infection and alterations in intestinal crypt epithelial cells that may be attributed to the envelope proteins gp70 and p15E and/or their precursor protein. Distinct similarities to the intestinal changes in the experimentally induced FeLV-feline AIDS syndrome are obvious, suggesting that naturally occurring feline AIDS variants may be responsible for FeLV-associated enteritis.     

Spironucleosis in Australian king parrots (Alisterus scapularis)

OBJECTIVE: To describe a syndrome of wasting, diarrhoea and mortality in Australian king parrots (Alisterus scapularis). DESIGN: Field observations and laboratory examinations. Procedure Pathological examinations were performed on 50 Australian king parrots with wasting and diarrhoea. Wet preparations of intestinal contents were examined by light microscopy. Tannins were extracted from acorns (Quercus sp) and tested for toxicity in mice. CLINICAL SIGNS AND EPIDEMIOLOGY: A syndrome of wasting, diarrhoea and mortality was observed in wild juvenile Australian king parrots in eastern Australia from 1984 to 2000. Sporadic cases and outbreaks of disease occurred from May to September in New South Wales, the Australian Capital Territory and Victoria. Outbreaks in the Australian Capital Territory in 1990 and 1991 were associated with parrots congregating to feed on acorns. Most affected birds failed to respond to treatment with dimetridazole and died 1 to 14 days after hospitalisation. Selected cases recovered following treatment with metronidazole. PATHOLOGY: Affected birds were emaciated, with faecal matting of feathers around the cloaca and yellow-green fluid, foamy intestinal contents. Abundant motile Spironucleus trophozoites were observed in wet preparations of faeces of clinically affected birds and intestinal contents of birds examined within 1 h of death. Protozoa were detected histologically in crypts of Lieberkühn in the intestine in association with exudation of mucus (catarrhal enteritis) or lymphoplasmacytic enteritis. Toxicology Tannin extracts from acorns induced periacinar hepatic necrosis in mice. CONCLUSION: Wasting, diarrhoea and mortality in wild juvenile Australian king parrots were associated with Spironucleus-like protozoa in the intestine. Acorns were not considered to be the cause of the syndrome.     

Bone marrow necrosis in a cat infected with feline leukemia virus

A one-year old castrated male cat was admitted to the hospital with vomiting and diarrhea. Laboratory examination revealed pancytopenia and positive for FeLV antigen. A bone marrow examination indicated necrosis of the nucleated cells. Based on these findings, the cat was diagnosed as bone marrow necrosis. Pancytopenia was effectively treated with corticosteroids. Re-examination of the bone marrow confirmed a recovery of normal hematopoietic cells with a infiltration of many macrophages. It is strongly suspected that the bone marrow necrosis in this case could be associated with a bone marrow suppression due to FeLV infection.     

Evaluation of the chicory inulin efficacy on ameliorating the intestinal morphology and modulating the intestinal electrophysiological properties in broiler chickens

Chicory (Cichorium intybus) belongs to plants of the Compositae family accumulating energy in the form of inulin fructan. Chicory, a prebiotic, is a fermentable oligosaccharide and oligofructose that may affect the intestinal mucosal architecture and the electrophysiological parameters. Therefore, this study was conducted to evaluate the effectiveness of adding chicory fructans in feed on the intestinal morphology and electrogenic transport of glucose in broilers. Four hundred, 1 day old broiler chicks were randomly divided into two groups (200 bird per group) for 5 weeks. The dietary treatments were (i) control, (ii) basal diets supplemented with the dried, grinded ground chicory pulp containing inulin (1 kg of chicory/ton of the starter and grower diets). In duodenum, dietary chicory increased the villus height and villus width and villus height to crypt depth ratio (p < 0.05), but the duodenal crypt depth remained unaffected (p > 0.05). However, in jejunum, the villus height, crypt depth and villus height to crypt depth ratio were decreased by dietary chicory compared with control birds (p < 0.05). In ileum, the villus height and villus crypt depth was decreased by dietary chicory supplementation compared with control (p < 0.05), but, the villus height to crypt depth ratio was increased (p < 0.05). Moreover, dietary chicory relatively affected the electrophysiological parameters of the intestine but did not reach significance. The amount of ΔIsc after d ‐glucose addition to the jejunal mucosa was numerically higher for chicory fed birds (19 μA/cm²) than control birds (10 μA/cm²). The percentage of increase in the Isc after d ‐glucose addition (ΔIsc %) was higher for chicory group upto (90%) of the control group. In colon, the actual Isc value and Isc after d ‐glucose addition was numerically higher for chicory fed birds than control birds (p > 0.05). Moreover, the conductance of jejunal and colonic tissues after d ‐glucose addition remained unaffected by the dietary chicory. In conclusion, addition of chicory to broilers diet increased the duodenal villus height, villus width and villus height to crypt depth ratio and decreased the villus height and crypt depth in both jejenum and ileum. Furthermore, dietary chicory relatively modified the small intestinal electrogenic transport of glucose in broilers.     

Atrophy of the primary lymphoid organs of meat pigeons in Italy associated with circoviruslike particles in the bursa of Fabricius

During a survey effected in a meat pigeon slaughterhouse of central Italy, atrophy of primary lymphoid organs (bursa of Fabricius and thymus) and hypoplasia of bone marrow were observed. Histologic, ultrastructural, and hematologic examinations were performed on a total of 80 randomly selected 30-day-old meat pigeons. By histologic studies, lymphocytic depletion and necrosis with cyst formations in the bursa of Fabricius were detected in all subjects that showed thymus and bursa atrophy at necropsy. Basophilic intranuclear inclusions were also observed in bursal cells. After ultrastructural studies, these inclusions were proved to be viral particles resembling circoviruslike particles in morphology and size. Severe lymphocytic depletion of the bursa was plausibly associated with the presence of the viral particles.     

Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog

An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.     

Fluoride intoxication in dairy calves

Chronic fluoride intoxication in dairy cattle, caused by feeding fluoride contaminated commercial feed, was previously described in a dairy herd. Dental fluorosis and a catastrophic decrease in milk yield were the foremost findings. In calves born to the fluoride intoxicated cows, congenital fluorosis was manifested by brown discoloration of enamel, enamel hypoplasia, brown mottling of bone, severe retardation of cartilage cell differentiation, atrophy of osteoblasts, osteopenia, atrophy of bone marrow cells, serous atrophy of bone marrow fat and severely stunted growth.