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A S Moore

Publications and source records attributed to A S Moore.

At least 37 records · Page 2Linked to original sources

The expression of P-glycoprotein in canine lymphoma and its association with multidrug resistance.

Canine lymphoma is a spontaneous, naturally occurring disease that is a model for non-Hodgkin's lymphoma in humans. Chemotherapy with antineoplastics results in a high rate of remission; however, relapse and clinical drug resistance are usually seen within 8-10 months. The P-glycoprotein product of the mdr gene is thought to function as an ATP-driven membrane drug efflux pump and appears to play an important role in tumor cell resistance. To assess the role of mdr gene products in drug resistance in canine lymphoma, membrane preparations of lymphoma cells from 31 dogs with high- or intermediate-grade lymphoma were subjected to Western blotting for detection of P-glycoprotein. In this study, one of 30 samples taken from dogs prior to receiving chemotherapy expressed detectable levels of P-glycoprotein. P-glycoprotein was also detected in biopsy samples from 3 of 8 dogs that had become resistant to chemotherapy. This pattern of expression is similar to that in human non-Hodgkin's lymphoma. These studies suggest that canine lymphoma is a useful model for studying multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Imidocarb residues in edible bovine tissues and in vitro assessment of imidocarb metabolism and cytotoxicity.

Imidocarb residues in liver and muscle were measured by HPLC after a single therapeutic dose to cattle (3 mg imidocarb dipropionate kg-1). Imidocarb and 7-ethoxycoumarin metabolism were compared in three different in vitro systems prepared from bovine liver: cultures of hepatocyte monolayers, precision-cut liver slices, and microsomes. The potential hepatotoxicity of imidocarb residues was tested on hepatocyte monolayers and assessed using the neutral red and lactate dehydrogenase leakage assays. The concentration of imidocarb (mean +/- SD) decreased between days 14 and 224 after treatment from 5.40 +/- 0.61 to 0.12 +/- 0.01 and from 1.05 +/- 0.31 to 0.06 +/- 0.02 microgram g-1 in liver and muscle, respectively. The depletion kinetics of imidocarb fitted a two-compartment model with alpha- and beta-phase half-lives of 31.7 and 48.5 days in liver and 34.9 and 120.7 days in muscle, respectively. Imidocarb metabolites were not detected in any in vitro system. 7-Ethoxycoumarin metabolism was found in all in vitro systems; the predominant metabolite produced by hepatocyte and liver slice cultures was umbelliferone glucuronide. Cytotoxicity of imidocarb (100 microM) to hepatocyte monolayers was maximal after 72 hr treatment and dose-dependent above 10 microM imidocarb. It is most likely that the hepatotoxicity of imidocarb is caused by the parent compound, because no evidence for imidocarb metabolism was found.

Animals↗

Toxicoses associated with the administration of mitoxantrone to dogs with malignant tumors: a dose escalation study.

Forty-four dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the chemotherapeutic agent mitoxantrone, when administered at dosages higher than what has been previously reported for use in dogs. After each dose was administered, dogs were evaluated for signs of toxicosis for 3 weeks or until the dog developed progressive disease, died, or was euthanatized. Forty dogs had been refractory to 1 or more treatment modalities (surgery, n = 26; chemotherapy other than mitoxantrone, n = 17; radiation, n = 2) prior to entering this study. Ten dogs were given mitoxantrone at a dosage of 5.5 mg/m2 of body surface, IV, every 3 weeks (39 total doses); 11 were given mitoxantrone at a dosage of 6.0 mg/m2, IV, every 3 weeks (26 total doses); and 23 were given mitoxantrone at a dosage of 6.5 mg/m2, IV, every 3 weeks (70 total doses). The most common signs of toxicosis were vomiting, anorexia, diarrhea, lethargy, and sepsis secondary to myelosuppression. Two dogs, both of which received the highest dosage, died of complications attributable to mitoxantrone administration. The prevalence of toxicoses was not associated with age, breed, sex, tumor type, number of doses, or dosage. Dogs did develop myelosuppression 7 days after they were given mitoxantrone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of butorphanol and cyproheptadine for prevention of cisplatin-induced vomiting in dogs.

Cisplatin was administered at a dosage of 50 mg/m2 of body surface to 69 dogs with various neoplasms. Dogs were randomly assigned to receive antiemetics according to 1 of the following 5 protocols: group 1, no antiemetic (control, n = 45 treatments); group 2, 0.4 mg of butorphanol/kg of body weight (n = 52 treatments); group 3, 0.2 mg of butorphanol/kg (n = 19 treatments); group 4, 2 mg of cyproheptadine/kg (n = 48 treatments); and group 5, 1 mg of cyproheptadine/kg (n = 10 treatments). Randomization was performed for each dog prior to each treatment. Butorphanol was administered IM immediately after completion of cisplatin infusion. Cyproheptadine was given orally 12 to 14 hours before and again immediately before cisplatin administration. The proportion of dogs that vomited in group 1 was 40 of 45 (89%). Butorphanol at a dosage of 0.4 mg/kg proved highly effective in preventing cisplatin-induced vomiting, reducing the proportion of dogs that vomited (10/52, 19%) compared with the control group.

Animals↗

Evaluation of mitoxantrone for the treatment of lymphoma in dogs.

Mitoxantrone was administered to 74 dogs with lymphoma at a dosage of 5.0 mg/m2 of body surface, IV, every 3 weeks. Thirty-four dogs had failed to respond to prior treatment with chemotherapeutic agents, which included doxorubicin (33 dogs). The remaining 40 dogs had not received prior treatment. Complete remission was determined in 19 of 74 dogs (26%), 10 of which had not received prior treatment. The median duration of remission for these 10 dogs was 94 days (range, 49 to 440 days, with 2 dogs still alive at 370 and 440 days, respectively). Nine dogs that had received prior treatment had complete remission that lasted for a median of 126 days (range, 42 to 792 days, with 1 dog still alive at 792 days). The combined remission rate (complete remission plus partial remission) was 41%. Toxicosis was minimal, developing in only 9 dogs and requiring hospitalization of 2 dogs. We concluded that the complete remission rate ascertained when mitoxantrone was the only treatment administered was low, compared with treatments that involved other chemotherapeutic agents; however, the combined remission rate of 41% indicated that mitoxantrone may be beneficial in the treatment of lymphoma in dogs.

Animals↗

Imidocarb depletion from cattle liver and mechanism of retention in isolated bovine hepatocytes.

Imizol injection (imidocarb) is used for the prevention and treatment of babesiosis in cattle. Studies in sheep indicate that imidocarb is retained in edible tissues (Aliu et al.). In the present study we have set up and validated a high-performance liquid chromatography based method to investigate the retention of imidocarb in cattle liver. Imidocarb was still detectable 224 d after a single therapeutic dose with a half-life of 42.7 d. The mechanism of imidocarb retention by bovine liver was modelled using isolated bovine hepatocytes. Incubations with isolated hepatocytes indicated that [14C]imidocarb binding was dependent on hepatocyte number and showed signs of saturation. Bound [14C]imidocarb could be eluted from hepatocytes with buffer and extracted with solvents. Equilibrium dialysis under denaturing conditions (Sun and Dent) indicated that 3% of the [14C]imidocarb was covalently bound to macromolecules. Although the hepatocyte preparations demonstrated the capacity for phase I and II 7-ethoxycoumarin metabolism no metabolites of [14C]imidocarb were found. Further in vitro binding studies involving sub-cellular fractionation indicated that [14C]imidocarb is partitioned largely in the nuclear fraction of bovine liver homogenates and that it binds to deoxyribonucleic acid.

Animals↗

Toxicoses and efficacy associated with administration of mitoxantrone to cats with malignant tumors.

Eighty-seven cats with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of mitoxantrone, a dihydroxyquinone derivative of anthracene, which was administered at 21-day intervals at dosages ranging from 2.5 to 6.5 mg/m2 of body surface, IV. Eleven of these cats were treated concurrently with radiation but were evaluated separately. Each cat was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the cat developed progressive disease, or until the cat's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. Although the primary purpose of this study was to determine a clinically useful dosage and to characterize the toxicoses associated with mitoxantrone administration, each cat was monitored for response to treatment. Forty-nine cats had been refractory to 1 or more treatment modalities prior to inclusion in this study. The most common signs of toxicosis after treatment with mitoxantrone were vomiting, anorexia, diarrhea, lethargy, sepsis secondary to myelosuppression, and seizures. Two cats died of complications that may have been attributed to mitoxantrone: 1 of cardiomyopathy and the other of pulmonary edema of an undetermined cause. Older cats were more likely to develop signs of toxicosis after the third or fourth mitoxantrone treatment than younger cats (P < or = 0.05). Cats with signs of toxicosis during the 21-day interval after administration of the first dose of mitoxantrone were significantly (P < or = 0.05) more likely to develop signs of toxicosis during the 21-day interval between the second and third doses of mitoxantrone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Multiple drug resistance.

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ATP Binding Cassette Transporter, Subfamily B, Mem↗

Use of the polymerase chain reaction and oligonucleotide probes for the rapid detection and identification of Carnobacterium species from meat.

The polymerase chain reaction (PCR) was used selectively to amplify specific rDNA sequences of Carnobacterium divergens, C. mobile, C. piscicola and C. gallinarum in purified DNA extracts, crude cell lysates and food samples. The PCR products were visualized by agarose gel electrophoresis and identified, at species level, by hybridization reactions with three specific oligonucleotide probes for C. divergens, C. mobile and C. piscicola/C. gallinarum designed from 16S rRNA sequence data. The PCR was sufficiently sensitive to amplify DNA from a single bacterium to detectable levels after 30 cycles of amplification. Both radioactive (32P) and non-radioactive alkaline phosphatase labelled probes was able to detect the PCR products. Detection was highly specific and the probes did not hybridize with DNA samples from any other of the bacterial species tested. These methods enabled the rapid and specific detection and identification of carnobacteria from pure cultures and samples of meat.

Base Sequence↗

Chemotherapy for intrathoracic cancer in dogs and cats.

The thoracic cavity contains numerous tissue types from which tumors may arise. Broadly speaking, the cavity is comprised of the pleural surfaces, the mediastinum and its enclosed viscera, and the lungs. Neoplasms arising from these structures are frequently advanced at the time of diagnosis, and surgery is rarely curative for malignant processes. Although reports describing anticancer chemotherapy use in dogs and cats for tumors of the thoracic cavity largely have been anecdotal, as advances are made in the chemotherapeutic management of comparable tumors in human cancer patients and as veterinarians become familiar with these compounds, use of antineoplastics as an adjunct to, or in place of, local treatment modalities should increase. This article reviews the epidemiology, clinical features, and diagnosis of pulmonary neoplasia; mediastinal neoplasia, particularly thymoma; and pleural neoplasia, with emphasis on mesothelioma. In addition, options for chemotherapy, derived from both the human and veterinary literature, are given for each tumor type.

Animals↗

Toxicoses associated with administration of mitoxantrone to dogs with malignant tumors.

One hundred twenty-nine dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the new dihydroxyquinone derivative of anthracene, mitoxantrone, which was administered IV at 21-day intervals at dosages ranging from 2.5 to 5 mg/m2 body surface area. Each dog was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the dog died, whichever came first. The number of dogs in each evaluation period were as follows: 1 dose (n = 129), 2 doses (n = 82), 3 doses (n = 43), 4 doses (n = 26), 5 doses (n = 19), 6 doses (n = 9), 7 doses (n = 6), 8 doses (n = 5), 9 doses (n = 3), and 10 doses (n = 1). The most common signs of toxicosis were vomiting, diarrhea, anorexia, and sepsis secondary to myelosuppression. None of the dogs died of complications resulting from mitoxantrone treatment. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of mitoxantrone were 95 times (P = 0.003) more likely to develop signs of toxicosis during the 21-day interval from the second dose of mitoxantrone. Similarly, dogs that developed signs of toxicosis during the 21-day interval from the administration of the second dose were 34 times (P less than 0.001) more likely to develop signs of toxicosis during the 21-day interval from the administration of the third dose. With each 1 mg/m2 increase in mitoxantrone, the odds of developing signs of toxicosis increased by 5.9 fold (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Efficacy of mitoxantrone against various neoplasms in dogs.

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.

Animals↗

Preclinical study of sequential tumor necrosis factor and interleukin 2 in the treatment of spontaneous canine neoplasms.

Recombinant human tumor necrosis factor and recombinant human interleukin 2 were administered in a sequential schedule to 30 dogs with a variety of spontaneous neoplasms. Dose escalation of both drugs was performed, and a maximally tolerated dose of recombinant human tumor necrosis factor of 125 mg/m2 i.v. for 3 days, followed by 1.5 x 10(6) units/m2 of recombinant human interleukin 2 s.c. for 9 days, was derived. Dose-limiting toxicities were primarily gastrointestinal; however, weakness and malaise were seen during therapy at doses higher than the maximally tolerated dose. No clinically significant hematological toxicities were seen at any dose level. Objective tumor responses were seen in dogs with oral mucosal melanoma and cutaneous mastocytoma. Because of the histological, behavioral, and epidemiological similarities between human and canine tumor types, the canine cancer patient provides a unique model for the preclinical evaluation of recombinant cytokine therapy.

Animals↗

Activity monitoring and an enzyme immunoassay for milk progesterone to aid in the detection of estrus.

The accuracy and efficiency of estrus detection using an electronic activity monitor tag in conjunction with an enzyme immunoassay for milk progesterone were studied during 55 observed estrous periods in 37 cows. At approximately 30 d postpartum, cows were equipped with an activity tag and visually observed for estrus, an activity tag with a flashing light-emitting diode, or both twice daily. Milk progesterone concentrations were determined from cows observed in estrus or with an activated tag. Mean daily activity was greater on the day of estrus than during any of the 3 d preceding or 3 d following estrus. Functioning activity tags correctly identified 55% of all visually observed estrous periods that coincided with low milk progesterone levels. The overall accuracy of a flag by the tag for identifying true estrus was 21%. The enzyme immunoassay for milk progesterone was in agreement with 98% of all visually observed estrous periods and false flags committed by the tags. Although the activity tags detected some cows in estrus, a more durable and reliable tag must be developed before it is of practical value to dairy producers.

Algorithms↗

Osteogenic sarcoma and myasthenia gravis in a dog.

A 7-year-old Saint Bernard developed muscular weakness 1 year after right forelimb amputation and adjuvant cisplatin chemotherapy for osteogenic sarcoma. Clinical and laboratory findings supported a diagnosis of myasthenia gravis, and the dog had clinical improvement in response to prednisone treatment. Two additional dogs with myasthenia gravis and osteogenic sarcoma were identified by review of the medical records of the University of California Veterinary Medical Teaching Hospital. Findings indicated that myasthenia gravis or other neuromuscular transmission disorders may be associated with muscular weakness in dogs with osteogenic sarcoma.

Animals↗

Evaluation of cisplatin-induced emesis in dogs with malignant neoplasia: 115 cases (1984-1987).

A retrospective review of the records of 115 dogs with 13 types of malignant tumors was performed in an attempt to identify factors that influence the degree of emesis observed within 24 hours after cisplatin therapy. Six groups were established on the basis of dosage of cisplatin and on the route of administration: 10 mg/m2 IV (n = 17), 40 mg/m2 IV (n = 10), 50 mg/m2 IV (n = 19), 60 mg/m2 IV (n = 7), 70 mg/m2 IV (n = 36), and 70 mg/m2 intra-arterially (IA; n = 26). Age, gender, weight, dose of cisplatin, route of administration (IV vs IA), and duration of infusion were evaluated. Increasing doses of cisplatin (P less than 0.01) and the IV route of drug administration (P less than 0.0006) were associated with an increased occurrence of vomiting in response to the first treatment. Anesthesia, performed in dogs that were given cisplatin IA, was a confounding variable that may have reduced the emetic potential of the drug after the dogs were awakened. If the dog vomited in response to the first treatment, there was a greater tendency to vomit after subsequent cisplatin treatments (P = 0.08). Multivariable analysis, after correcting for the effects of age, gender, and weight, indicated that high doses of cisplatin (P less than 0.001) and lower weight of the dog (P less than 0.04) were significantly associated with an increased likelihood of vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunohistochemical evaluation of intermediate filament expression in canine and feline neoplasms.

Specimens of neoplastic tissues from 19 dogs and 4 cats were examined immunohistochemically for intermediate filament expression, using commercially available antibodies. Staining was observed in a wide range of tumor tissues and in normal internal controls by use of antibodies to vimentin, desmin, glial fibrillary acidic protein, and low and high molecular weight cytokeratins. Intermediate filament expression was found to be consistent with light and/or electron microscopic findings, and hence believed to be an accurate indicator of tumor histogenesis in cats and dogs. Three fixatives were evaluated for their relative abilities to preserve antigenicity. Absolute alcohol was superior to B5 fixative and both were superior to formalin. Some tissues that clearly displayed intermediate filament antigens with alcohol and B5 fixative failed to stain when fixed in formalin.

Adenocarcinoma↗