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- Author or Editor: Gregory M. Moore x
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Abstract
Objective
To determine and evaluate the efficacy of the dose range of tilmicosin phosphate fed to pigs for control of pneumonia attributable to Actinobacillus pleuropneumoniae during episodes of clinical disease in commercial herds.
Design
12 trials were run in 9 geographic locations in herds with a history of pneumonia caused by A pleuropneumoniae.
Animals
Clinically normal male and female pigs of various body weights.
Procedure
Two doses of tilmicosin phosphate (200 and 400 µg/g) and a 0 dose were administered in the feed for 21 days. Variables for determining efficacy were daily independent composite clinical impression score, individual pig weight, mortality, percentage of pneumonic involvement, and frequency of isolation of bacterial pathogens.
Results
Medicated pigs had significantly lower mortality attributed to pneumonia than did nonmedicated pigs. In trials with confirmed pneumonia caused by A pleuropneumoniae or Pasteurella multocida, weight gain, feed conversion, and clinical impression scores were significantly improved in the pigs receiving 200 or 400 µg/g of tilmicosin, compared with nonmedicated pigs.
Conclusions
The clinical field trials reported here confirm that tilmicosin in the feed at 200 µg/g is effective for control of swine pneumonia attributable to A pleuropneumoniae or P multocida.
Clinical Relevance
Under the moderate natural challenge conditions encountered, tilmicosin at 400 µg/g was not different from tilmicosin at 200 µg/g.
Abstract
Objective—To determine toxic effects of streptozocin given in combination with a diuresis protocol in dogs and establish whether streptozocin is efficacious in treatment of pancreatic islet cell tumors in dogs.
Design—Retrospective study.
Animals—17 dogs.
Procedure—Medical records were reviewed to obtain information regarding signalment, tumor stage and staging tests performed, number of streptozocin treatments, adverse effects, results of biochemical and hematologic monitoring during streptozocin treatment, tumor dimensions, duration of normoglycemia, and date of death, when applicable. Dogs were compared with a historical control group of 15 dogs treated surgically and medically.
Results—58 treatments were administered to the 17 dogs. Only 1 dog developed azotemia. Serum alanine aminotransferase activity increased in some dogs but decreased when treatment was discontinued. Hematologic toxicoses were rare. Vomiting during administration was uncommon but occasionally severe. Two dogs developed diabetes mellitus after receiving 5 doses. Median duration of normoglycemia for 14 dogs with stage-II or -III insulinoma treated with streptozocin was 163 days (95% confidence interval, 16 to 309 days), which was not significantly different from that for the control dogs (90 days; 95% confidence interval, 0 to 426 days). Two dogs had rapid resolution of paraneoplastic peripheral neuropathy, and 2 others had measurable reductions in tumor size.
Conclusions and Clinical Relevance—Results suggest that streptozocin can be administered safely to dogs at a dosage of 500 mg/m2, IV, every 3 weeks when combined with a protocol for induction of diuresis and may be efficacious in the treatment of dogs with metastatic pancreatic islet cell tumors. (J Am Vet Med Assoc 2002;221:811–818)
Objectives
To evaluate effects of tilmicosin when used in fever-based and metaphylactic treatment programs to attenuate acute undifferentiated bovine respiratory disease (BRD) in cattle that recently arrived at feedlots, and to evaluate the effects of tilmicosin for the treatment of BRD.
Design
Randomized-block controlled study.
Animals
1,639 calves from livestock auctions.
Procedures
Cattle were assigned to 3 groups. Cattle in the nonmedicated (control) group were not given antibiotics during processing. Cattle in the fever-based treatment group were given tilmicosin (10 mg/kg [4.5 mg/lb] of body weight, SC) during processing when their rectal temperature was ≥ 40 C (104 F). All cattle in the metaphylactic treatment group were given tilmicosin (10 mg/kg, SC) during processing. Calves with BRD were treated with tilmicosin (10 mg/kg, SC).
Results
Morbidity rates in the metaphylactic (30.4%) and fever-based (44.7%) treatment groups were less than that for the nonmedicated group (54.8%). Mortality rate for the metaphylactic group during the first 28 days (1.1%) and during the entire study (1.7%) was less than that for the nonmedicated group (3.3 and 4.6%, respectively). Differences were not observed in therapeutic response rates among calves with BRD that were treated.
Clinical Implications
Fever-based and metaphylactic treatment programs that used tilmicosin decreased the prevalence of BRD and improved growth of calves. Metaphylactic treatment decreased the number of fatalities caused by BRD in high-risk calves. Fever-based treatment was less effective than metaphylactic treatment for decreasing the prevalence of BRD in newly arrived cattle. (J Am Vet Med Assoc 1998,212:1919–1924)
Summary
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. Median neutrophil count for dogs that received mitoxantrone at a dosage of 6.5 mg/m2 was 2,800 cells/μl (range, 300 to 4,600 cells/μl); median neutrophil count for dogs that received mitoxantrone at a dosage of 6.0 mg/m2 was 3,800 cells/μl (range, 600 to 10,400 cells/μl); and median neutrophil count for dogs that received mitoxantrone at a dosage of 5.5 mg/m2 was 4,500 cells/μl (range, 1,700 to 16,100 cells/μl).
Abstract
Objective
To determine the effective dosage of tilmicosin phosphate when fed to pigs for the control of pneumonia attributable to Actinobacillus pleuropneumoniae.
Design
Randomized complete block design, with initial weight as the blocking factor.
Animals
Seeder pigs were used to infect clinically normal male and female pigs weighing between 13.6 and 36.3 kg at each of 4 trials.
Procedure
Five doses of tilmicosin phosphate (0, 100, 200, 300, and 400 µg/g) were fed to pigs for 21 days. Pigs received experimental feeds 7 days before the seeder pigs were placed into pens. Feeding continued for an additional 14 days, with seeder pigs removed 3 to 8 days after placement. All pigs were euthanatized and necropsied, with lung bacterial flora and percentages of pneumonic involvement determined.
Results
Improvement in clinical impression score, daily rectal temperature, and weight gain were seen for all doses of tilmicosin, compared with controls. For the same variables, tilmicosin administered at 200 to 400 µg/g resulted in improvements over the 100 µg/g dose.
Conclusions
Data indicate that tilmicosin phosphate fed to pigs at 200 to 400 µg/g is effective in controlling and preventing A pleuropneumoniae-induced pneumonia, when administered in feed for 21 days.
Summary
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.
Summary
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 (>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.
Summary
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 < 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 < 0.001). The performance status (modified Karnofsky performance scheme) of each dog was not adversely affected to a significant extent by mitoxantrone-induced toxicosis until the fifth dose (P = 0.0008). Cardiac toxicosis was not detected. Mitoxantrone was also administered iv to 4 clinically normal dogs, at a dosage of 5 mg/m2 of body surface area, a decrease in the neutrophil count was seen, with the nadir occurring on day 10 (mean ± sem: 1,159 ± 253 cells/μl; range, 480 to 1,680 cells/μl). Tumor-bearing dogs did not seem to have the same degree of myelosuppression (mean ± sem, 6,263 ± 1,230 cells/μl; range, 228 to 18,600 cells/μl).
Summary:
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 ≤ 0.05). Cats with signs of toxicosis during the 21-day interval after administration of the first dose of mitoxantrone were significantly (P ≤ 0.05) more likely to develop signs of toxicosis during the 21-day interval between the second and third doses of mitoxantrone. Similarly, cats that became toxic during the 21-day interval between the second and third doses were significantly (P ≤ 0.05) more likely to become toxic during the 21-day interval between the third and fourth doses. Controlling for age, breed, and dose of mitoxantrone, cats that became toxic after the first treatment were 2.4 times more likely to have poor performance status than the non toxic cats. Tumor-bearing cats had some degree of myelosuppression 7 days after they were given mitoxantrone at 6.5 mg/m2, iv (median neutrophil count, 2,440 cells/μl; range, 1,595 to 6,300 cells/μl).
Complete or partial remission (> 50% reduction volume reduction) was obtained in 18.4% (14/76) of cats given mitoxantrone alone. Remission was recorded in 17.6% (9/51) of cats with carcinoma, 11.8% (2/17) of the cats with lymphoma, and 37.5% (3/8) of the cats with sarcoma.
Because the cats with squamous cell carcinoma had a poor response to mitoxantrone, an additional 11 cats with squamous cell carcinoma were treated concurrently with radiation (44 to 65 Gy, 10 to 15 fractions) over a 3-week period beginning at the time the first dose of mitoxantrone (2.5 to 6 mg/m2) was given. None of these 11 cats had any signs of toxicosis attributable to mitoxantrone chemotherapy. Eight cats had a complete remission (median, 170 days; range, 28 to 485 days), and 1 had a partial remission that lasted 60 days.
Summary
Long-term follow-up information pertaining to 162 dogs with appendicular osteosarcoma treated by amputation alone was collected from 17 veterinary institutions. The majority (72.5%) of dogs died or were euthanatized because of problems documented to be related to metastases. The first clinically apparent sites of metastasis were the lungs (60.8% of total), the skeleton (5.2%), or both (4.6%). A Kaplan-Meier survivorship distribution was plotted on the basis of available survival time data in all 162 dogs. The mean and median survival times were estimated to be 19.8 and 19.2 weeks, respectively, and the 1- and 2-year survival rates were estimated to be 11.5 and 2.0% respectively.
Statistically significant relationships were not found between survival time and reporting institution, gender, site of primary tumor, whether the primary tumor was proximally or distally located, whether the primary tumor was located in the forelimb or hind limb, whether presurgical biopsy was performed, and whether death was tumor related. A significant (P < 0.01) quadratic relationship was found between age and survival time. Survival time was longest in dogs 7 to 10 years old and was shorter in older and younger dogs.
