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Biomedical subjects

A M Legendre

Publications and source records attributed to A M Legendre.

At least 19 recordsLinked to original sources

Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals.

OBJECTIVE: To determine proportions of cats in which feline infectious peritonitis (FIP) was diagnosed on an annual, monthly, and regional basis and identify unique characteristics of cats with FIP. DESIGN: Case-control study. SAMPLE POPULATION: Records of all feline accessions to veterinary medical teaching hospitals (VMTH) recorded in the Veterinary Medical Data Base between January 1986 and December 1995 and of all feline accessions for necropsy or histologic examination at 4 veterinary diagnostic laboratories. PROCEDURE: Proportions of total and new feline accessions for which a diagnosis of FIP was recorded were calculated. To identify characteristics of cats with FIP, cats with FIP were compared with the next cat examined at the same institution (control cats). RESULTS: Approximately 1 of every 200 new feline and 1 of every 300 total feline accessions at VMTH in North America and approximately 1 of every 100 accessions at the diagnostic laboratories represented cats with FIP. Cats with FIP were significantly more likely to be young, purebred, and sexually intact males and significantly less likely to be spayed females and discharged alive than were control cats. The proportion of new accessions for which a diagnosis of FIP was recorded did not vary significantly among years, months, or regions of the country. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that FIP continues to be a clinically important disease in North America and that sexually intact male cats may be at increased risk, and spayed females at reduced risk, for FIP. The high prevalence of FIP and lack of effective treatment emphasizes the importance of preventive programs, especially in catteries.

Age Factors↗

Canine antibody response to Blastomyces dermatitidis WI-1 antigen.

OBJECTIVE: To assess whether dogs with blastomycosis produce antibodies against the WI-1 and A-antigens of Blastomyces dermatitidis and whether the antibodies are useful in serodiagnosis. SAMPLE POPULATION: 359 serum samples obtained from 245 dogs. PROCEDURE: 233 samples from 122 dogs with blastomycosis, and 1 sample each from 24 dogs with suspected blastomycosis, 51 control dogs without infection, and 48 healthy dogs from an enzootic region were obtained. Antibodies against WI-1 antigen were detected by radioimmunoassay (RIA). Serum samples were tested in parallel for antibodies against the A-antigen of B dermatitidis by commercial agar-gel immunodiffusion (AGID) in a reference laboratory. RESULTS: Antibodies were detected in 92% of infected dogs by RIA and in 41 % by AGID. For 29 serum samples that were obtained 11 to 1,545 days after diagnosis, antibodies were detected in 92% of samples by RIA and 7% by AGID. For 93 serial serum samples from 29 dogs with blastomycosis, the mean anti-WI-1 titer was 1:18,761 at the time of diagnosis, and decreased to a mean of 1:1,338 by 210 days after treatment was initiated. Of 24 dogs with suspected infection, antibodies were detected in 67% by RIA and 33% by AGID. Control dogs without blastomycosis had no detectable antibodies in either assay. Thus, sensitivity was 92% for RIA and 41 % for AGID, and specificity was 100% for both tests. CONCLUSIONS AND CLINICAL RELEVANCE: Anti-WI-1 antibodies are readily detected by RIA in dogs with blastomycosis. Titers become high, decline during treatment, and persist for months. Anti-A antibodies are sometimes detected with AGID, but these decrease quickly.

Animals↗

Fecal shedding of feline coronavirus in adult cats and kittens in an Abyssinian cattery.

OBJECTIVE: To determine patterns of fecal shedding of feline coronavirus (FCV) by cats, age at which kittens first began to shed FCV in their feces, and whether there was any relationship between fecal shedding of FCV and serum antibody titers in adult cats or kittens. DESIGN: Prospective observational study. ANIMALS: 15 adult cats and 18 kittens from a single cattery. PROCEDURE: Blood and fecal samples were collected from adult cats every other month for 13 months. Serum FCV antibody titers were measured by use of an indirect immunofluorescence assay. A reverse-transcriptase, nested polymerase chain reaction assay was used to detect FCV in feces. Blood and fecal samples were collected from kittens at approximately 2-week intervals from 3 weeks to 15 weeks of age. RESULTS: Adult cats shed FCV intermittently. All adult cats shed virus in their feces at least once during the year, and 4 of 15 shed virus > 75% of the time. Serum antibody titer was not significantly associated with shedding of FCV. For the kittens, median age at the time FCV was first detected in feces was 67 days (range, 33 to 78 days). All except 1 of the kittens was found to be shedding virus in their feces before or at the time of seroconversion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that serum FCV antibody titers are not a good indicator of shedding of FCV in the feces. Kittens may shed FCV in their feces before they seroconvert, and all kittens in a cattery in which FCV infection is endemic may be infected before 12 weeks of age.

Animals↗

Owner experiences with home use of a gastrostomy tube in their dog or cat.

OBJECTIVE: To describe owner experiences with gastrostomy tubes used at home. DESIGN: Telephone survey. ANIMALS: 20 cats and 5 dogs. PROCEDURE: Owner's opinions obtained by phone interview. RESULTS: Although 32% (8/25) of owners were initially reluctant to feed their cat or dog through the gastrostomy tube, 92% (22/24) of owners became comfortable with the procedure. Eighty-four percent (21/25) of owners were able to feed their dog or cat unassisted; 16% (4/25) required another person to help. Median time required for feeding was 19.8 minutes. Ninety-six percent (24/25) of owners believed their dog or cat was comfortable with the procedure. Eighty-four percent (21/25) of owners experienced complications or difficulties. Most problems involved bandage maintenance, administration of food through the syringe and tube, or acquisition of syringes and special foods. Ninety-six percent (22/23) of owners would be willing to use a gastrostomy tube again. CLINICAL IMPLICATIONS: Most owners had positive experiences with the feeding experience and would be willing to use gastrostomy tube feeding again. Difficulties encountered by owners were not serious and could be avoided by specific client instruction.

Animals↗

Amputation and dexniguldipine as treatment for canine appendicular osteosarcoma.

The biological behavior of osteosarcoma in dogs is similar to that in humans and the dog has been suggested as a model for the disease in humans. Because occult metastatic disease is common at presentation, systemic therapy is necessary. The dihydropyridine, dexniguldipine hydrochloride (B859-35), is a potent inhibitor of protein-kinase-C(PKC)-stimulated cell proliferation and has shown therapeutic activity in experimentally induced neuroendocrine hamster lung tumors and in a mammary cancer cell line. In human osteosarcoma cell lines, PKC activity can be down-regulated, resulting in increased sensitivity to cisplatin. Since these results supported the involvement of PKC inhibitors in the therapeutic management of osteosarcoma, we performed a prospective, randomized clinical trial using dogs with naturally occurring appendicular osteosarcoma to determine the therapeutic potential of dexniguldipine. Dogs received either no drug treatment (control group, n = 8), standard treatment (e.g., cisplatin, n = 14), or dexniguldipine treatment (n = 14) following amputation. Dexniguldipine- and cisplatin-treated dogs had a longer median remission duration and survival time than untreated dogs (P < 0.05); however, dexniguldipine-treated dogs had a shorter survival time than cisplatin-treated dogs (P < 0.05). The results of this study demonstrate that dexniguldipine has significant activity in the inhibition of canine osteosarcoma micrometastases. The identification of a tumor model that may be responsive to this class of antiproliferative agents warrants further clinical investigation to determine the optimum dosage of dexniguldipine and the role it may have in the therapeutic management of canine osteosarcoma.

Amputation, Surgical↗

Immunological and chemical characterization of glycoproteins in IEF fractions of Blastomyces dermatitidis yeast lysate antigen.

After isoelectric focusing (IEF), fractions of a Blastomyces dermatitidis yeast lysate antigen were analysed for the presence of glycoproteins that may lead to cross-reactivity in immunoassays for the diagnosis of blastomycosis. Five major glycoproteins were apparent, two of which showed cross-reactivity when used in Western blots with sera obtained from dogs with histoplasmosis and coccidioidomycosis. These five glycoproteins were characterized for linkage to the proteins using N-glycosidase F (NGF) and for their lectin binding properties. The cross-reactive 235- and 160-kDa glycoproteins were found to possess mainly O-linked, high-mannose-type carbohydrates, and periodate-mediated oxidation of these molecules eliminated cross-reactivity observed with heterologous sera. Thus, the periodate-treated IEF antigens described here may be useful in solid-phase enzyme immunoassays for the diagnosis of blastomycosis.

Animals↗

Investigation of the effects of hyperthyroidism on renal function in the cat.

This study evaluated the effects of thyroxine on renal function in the cat. Baseline serum thyroxine (T4) concentrations, clinicopathologic data (complete blood count [CBC], serum chemistry panel, urinalysis), and nuclear medicine determinations of glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and effective renal blood flow (ERBF) were measured in 10 normal adult cats. Cats were then injected with thyroxine (T4) (50 micrograms/kg SQ) daily for 30 d to induce hyperthyroidism. Clinicopathologic and nuclear medicine studies were repeated at 30 d. Cats injected with thyroxine had significant increases in T4, GFR, and ERBF and significant declines in serum creatinine and blood urea nitrogen (BUN) values. Administration of high doses of exogenous thyroxine to cats results in significant stimulation of renal function.

Animals↗

Hematologic and systemic toxicoses associated with carboplatin administration in cats.

OBJECTIVE: To determine prevalence and severity of carboplatin-induced dose-limiting toxicoses in the cat. ANIMALS: 9 healthy, 6- to 7-month-old cats weighing 4.7 (range, 3.0 to 6.5) kg. PROCEDURE: Cats were given a single i.v. bolus of carboplatin at a dosage of 150 (n = 3), 200 (n = 3), or 250 (n = 3) mg/m2 of body surface area. RESULTS: Dose-limiting neutropenia and thrombocytopenia were significant in all cats given carboplatin at 200 or 250 mg/m2. Weight loss, changes in appetite, and evidence of respiratory difficulty, as well as vomiting, diarrhea, or lethargy were not observed at any time during the 28-day period. At a highest dosage (250 mg/m2), the neutrophil nadir (560 +/- 303 neutrophils/microliters) was observed on day 17 and the platelet count nadir (96,500 +/- 11,815 platelets/microliters) was observed on day 14 after carboplatin administration. CONCLUSIONS: Carboplatin appears to be safe and clinically well-tolerated when given i.v. as a single bolus at a dosage of 200 mg/m2 to clinically normal cats. The dose-limiting toxicity of a single i.v. administered bolus is neutropenia. The nadir of a 200 mg/m2 i.v. administered dose occurs on day 17 (1,110 +/- 165 neutrophils/microliters) and neutropenia (< 2,000 neutrophils/microliters) lasts from day 14 through day 25 after carboplatin administration. CLINICAL RELEVANCE: The fatal dose-related pulmonary toxicosis observed in cisplatin-treated cats was inapparent in carboplatin-treated cats. To adequately determine the therapeutic role of carboplatin in tumor-bearing cats, a moderately tolerated dose of carboplatin of 200 mg/m2 given i.v. once every 4 weeks should be considered.

Animals↗

Serum granulocyte colony-stimulating factor (G-CSF) and interleukin-1 (IL-1) concentrations after chemotherapy-induced neutropenia in normal and tumor-bearing dogs.

Hematopoiesis is regulated by complex interactions of hematopoietic growth factors known as colony-stimulating factors and interleukins. We used sensitive bioassays to quantitate serum granulocyte colony-stimulating factor (G-CSF) and interleukin-1 (IL-1) concentrations in normal and tumor-bearing dogs following administration of myelosuppressive chemotherapy (vincristine, doxorubicin, cyclophosphamide). Serum G-CSF and IL-1 increased during the neutrophil nadir in 13 of the 16 dogs. Serum G-CSF concentrations were significantly increased in normal and in tumor-bearing dogs on neutropenic compared to non-neutropenic days. Serum IL-1 concentrations increased significantly on neutropenic days in normal dogs but not in tumor-bearing dogs. A marked neutrophilia was observed in normal dogs, but not in tumor-bearing dogs, following the increases in serum G-CSF and IL-1 concentrations (days 7, 8, and 9, p < 0.05). Normal dogs produced significantly more G-CSF on neutropenic days compared to dogs with lymphoma. On non-neutropenic days, serum IL-1 concentrations were significantly increased in dogs with lymphoma and in dogs with nonlymphoid malignancies compared to normal dogs. These results suggest an important role for G-CSF and IL-1 in hematopoietic recovery after chemotherapy-induced myelosuppression and document an altered hematopoietic regulation in animals with malignancy compared to normal subjects.

Animals↗

The frequency of micronuclei in lymphocytes of dogs with osteosarcoma: a predictive variable for tumor response during cisplatin chemotherapy.

To our knowledge, there are no features identifiable at the time of diagnosis or during treatment that can assist the clinician in predicting the response to cisplatin therapy in dogs with osteosarcoma. In this study, we describe a direct relationship between the percentage of G0 lymphocytes containing micronuclei following exposure to one dose of cisplatin in vivo and tumor response in dogs with osteosarcoma. The response of tumors to chemotherapy is thought to be a function of the drug's pharmacological properties (e.g., peak plasma concentration and elimination half-life); however, a relationship between platinum DNA adduct levels in leukocyte DNA and tumor response has been observed by others, suggesting that clinical resistance to platinum drugs is attributable to DNA repair functions of the host, and thus the degree of cytotoxicity is similar across all cell types. Our results support this hypothesis. Those dogs receiving cisplatin chemotherapy and having a micronuclear frequency of greater than 10% had median remission and survival times of 68.3 and 79.0 weeks, respectively, whereas those dogs with a micronuclear frequency of less than 10% had median remission and survival times of 14.1 and 17.9 weeks, respectively.

Analysis of Variance↗

Separation of feline bone marrow cells by counterflow centrifugal elutriation. Identification and isolation of presumptive early and late myeloid/erythroid progenitors.

Counterflow centrifugal elutriation (CCE) has been used to separate nucleated cells from mammalian bone marrow on the basis of size with the resultant isolation of hematopoietic cells in varying stages of lineage development. We examined the feasibility of identifying and isolating such cells from feline bone marrow. CCE was performed with a Beckman J6MI centrifuge and a Sanderson chamber, using a fixed rotor speed of 3000 rpm and collection of cells at (1) 16-, (2) 21-, (3) 25-, (4) 32 ml/min, and (5) a rotor off fraction. Recovery of the total input cells in four replicate experiments averaged 86%, with the maximum number of recovered cells in fraction 4. Analysis by flow cytometry and monoclonal antibodies revealed mononuclear cells in fractions 1 and 2 and early and late differentiating myeloid/erythroid cells in fractions 2 through 5. T lymphocytes and alloreactivity in a mixed lymphocyte reaction (MLR) were restricted to fractions 1 and 2; removal of T cells and MLR activity was accomplished by immunomagnetic depletion. In vitro cultures for clonogenic cells revealed CFU-GM and BFU-E colonies in fractions 2 through 5, with fraction 4 containing the greatest absolute number of myeloid colonies and fractions 3 and 4 the majority of the erythroid colonies. More important, in examining the plating efficiency for clonogenic cells in the different fractions it was found that this increased significantly in fractions 2 and 3 when the culture time was extended from 7 to 14 days; in contrast, fractions 4 and 5 reached their maximum plating efficiency within 7 days with no further increase on day 14. We interpret these findings to indicate the presence of late differentiating progenitors in the large-cell size fractions 4 and 5, while the smaller mononuclear cells in fractions 2 and 3 represent an earlier, more primitive population of hematopoietic cells requiring an extended time in culture for full colony development.

Animals↗

Comparison of body surface area-based and weight-based dosage protocols for doxorubicin administration in dogs.

Pharmacokinetics and toxicity of a single dose of doxorubicin, at dosages of 30 mg/m2 of body surface area and 1 mg/kg of body weight, were compared in 17 dogs. Effects of doxorubicin on complete blood cell count, platelet count, and the dogs' clinical condition were evaluated for 14 days. Cluster analysis, on the basis of clinical signs of doxorubicin toxicosis at the 30-mg/m2 dosage, revealed that 6 of 7 small dogs (< or = 10 kg) became ill, whereas 7 of 10 large dogs (> 10 kg) remained clinically normal. Small dogs that received doxorubicin at a dosage of 30 mg/m2 had higher peak plasma concentrations, greater area under the curve for plasma drug concentration vs time, longer drug elimination half-lives, greater volumes of distribution, and more clinical signs of toxicosis than had large dogs (P < or = 0.05). Five of 9 small dogs that received doxorubicin at a dosage of 30 mg/m2 developed severe myelosuppression (< 1 x 10(3) granulocytes/microliters). In contrast to the toxicoses with body surface area-based dosing, myelosuppression was not induced in small dogs that received doxorubicin at a dosage of 1 mg/kg. In small and large dogs given doxorubicin at a dosage of 1 mg/kg, pharmacokinetic characteristics and clinical signs of toxicosis were similar. Mean WBC counts and granulocyte counts for all dogs were lower on day 7 with 30 mg of doxorubicin/m2 (n = 17), compared with that for 1 mg of doxorubicin/kg (n = 14; P < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Isolation and functional studies on feline bone marrow derived macrophages.

In this report, we describe an in vitro culture method for feline bone marrow cells, which yields large numbers of quiescent macrophages after 14 days of culture. The bulk of the cultured cell population consists of macrophages as assessed by morphology, macrophage specific cytochemistry, and phagocytosis. The remaining cells were lymphocytes, bone marrow stromal cells, fibroblasts and occasional polymorphonuclear leukocytes. While resting cells produced no detectable interleukin 1, stimulation with lipopolysaccharide (LPS) induced the production of biologically active interleukin 1. After 6 h LPS stimulation, mRNA for tumor necrosis factor alpha and interleukin 1 beta was detectable. The absence of mRNA in unstimulated cells indicates cultured macrophages were not activated until stimulated by LPS or plastic adherence. This approach provides a useful means to measure potential modulatory effects by virus infections or other agents upon feline macrophage gene expression.

Animals↗

Evaluation of a commercial DNA probe assay for the identification of clinical isolates of Blastomyces dermatitidis from dogs.

A DNA probe assay (AccuProbe, Gen-Probe, Inc., San Diego, CA) for culture confirmation of Blastomyces dermatitidis in clinical isolates was evaluated using 72 isolates of B. dermatitidis (62 dog isolates, five from other animals, four human isolates and one soil isolate). In addition, specificity determinations were performed using 28 American Type Culture Collection (ATCC) fungal isolates, other than B. dermatitidis, representing 21 different genera. The non-isotopic hybrid protection assay, that can be performed in less than 1 h, uses a chemiluminescent acridinium ester DNA probe that is homologous to ribosomal RNA sequences of B. dermatitidis. Positive results were obtained with all 72 B. dermatitidis isolates (100% sensitivity). In addition, no positive results were evidenced with the other 28 non-B. dermatitidis fungal isolates, including six strains of Histoplasma capsulatum (100% specificity).

Animals↗

Comparative pharmacokinetics of the photosensitizer tin-etiopurpurin in dogs and rats.

Photodynamic therapy is a promising new treatment for local eradication of cancer. Little work has been done to define the pharmacokinetics of photodynamic drugs or the variability in drug disposition that may occur between different species and pathophysiological states of tissues. Pharmacokinetic studies of tin-etiopurpurin (SnET2), a lipophilic photosensitizer, were conducted on six Beagle dogs and six Sprague-Dawley rats. Blood was collected up to 24 h following drug administration for measurement of tin-etiopurpurin concentration. Dogs and rats were euthanatized 24 h post-administration and tissues were collected for drug analyses. The plasma drug concentrations were best described by a 2-compartment model (Ct = Ae-alpha t + Be-beta t). Median distribution and elimination half-lives were 0.24 and 0.34 h and 10.21 and 5.25 h for dogs and rats, respectively. The apparent volumes of distribution were 4.26 +/- 1.75 L/kg for dogs and 1.84 +/- 0.36 L/kg for rats. Systemic clearance was 7.56 +/- 2.45 ml/kg/min and 6.63 +/- 0.91 ml/kg/min for dogs and rats, respectively. Drug was detected in all tissues analyzed 24 h after drug administration. Drug was detected only sporadically in skin and muscle and was generally below the limit of detection of the assay. Where comparisons could be made, concentrations of SnET2 were significantly greater in all tissues except jejunum of rats compared to dogs 24 h after drug administration.

Animals↗

Comparison of four test kits for feline leukemia virus antigen.

The sensitivity and specificity of 4 commercial FeLV ELISA kits, using blood, were compared with results of virus isolation from blood and immunofluorescent antibody (IFA) testing on blood. Significant differences were not found among the 4 ELISA kits. Marked decrease in sensitivity of the ELISA kits was detected when virus isolation was used as the standard of positivity rather than the IFA test. Virus isolation was a more sensitive indicator of early infection, with marked discrepancy among results obtained by virus isolation, ELISA, and the IFA test. Results became progressively more concordant as infection became fully established. Cats FeLV-positive by virus isolation alone were more likely to eliminate viremia. All cats FeLV-positive by IFA testing remained persistently viremic. Virus isolation, ELISA, and IFA testing appear to differ in their prognostic value. The use of blood rather than serum for the ELISA resulted in several discordant results. Six cats were FeLV-positive by ELISA when blood was tested but were FeLV-negative when serum was tested. Positive ELISA results were obtained for 4 of these cats when serum was tested, using extended incubation to increase sensitivity. It is possible that blood may actually be more sensitive than serum for use of the ELISA method.

Animals↗