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1.
OBJECTIVE: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of ifosfamide in tumor-bearing cats. ANIMALS: 38 cats with resected, recurrent, or metastatic sarcomas. PROCEDURE: The starting dosage of ifosfamide was 400 mg/m(2) of body surface area, IV, and dosages were increased by 50 to 100 mg/m(2) in cohorts of 3 cats. To protect against urotoxicosis, mesna was administered at a dosage equal to 20% of the calculated ifosfamide dosage. Diuresis with saline (0.9% NaCl) solution before and after administration of ifosfamide was used to minimize nephrotoxicosis. Samples for pharmacokinetic analysis were obtained after the MTD was reached. RESULTS: 38 cats were entered into this phase I study and were administered a single dose of ifosfamide at various dosages. The MTD was 1,000 mg/m(2), and neutropenia was the DLT. Seven of 8 episodes of neutropenia were on day 7 after treatment, and 1 cat developed severe neutropenia on day 5. Adverse effects on the gastrointestinal tract were generally mild and self-limiting, the most common of which was nausea during ifosfamide infusion. One cat had signs consistent with a drug-induced hypersensitivity reaction. There were no episodes of hemorrhagic cystitis or nephrotoxicosis. Correlations between pharmacokinetic variables and ifosfamide-associated toxicoses were not found. Preliminary evidence of antitumor activity was observed in 6 of 27 cats with measurable tumors. CONCLUSIONS AND CLINICAL RELEVANCE: The dosage of ifosfamide recommended to treat tumor-bearing cats is 900 mg/m(2) every 3 weeks. This dosage should be used in phase II clinical trials.  相似文献   

2.
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)  相似文献   

3.
OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.  相似文献   

4.
During the first part of a study, cats were inoculated with Cryptococcus neoformans via the following routes: intradermal, intranasal, IV, and intracisternal. Only use of the IV route of inoculation consistently induced disseminated cryptococcosis. In the second part of the study, disseminated cryptococcosis was experimentally induced in cats via IV inoculation of C neoformans. One month after inoculation, 3 cats were treated with ketoconazole (10 mg/kg of body weight/d) and 3 cats were treated with itraconazole (10 mg/kg/d) for 3 months. One of the ketoconazole-treated and 2 of the itraconazole-treated cats also had cryptococcosis of the CNS when treatment was begun. During treatment, serum cryptococcal antigen titer progressively decreased in all cats. Abnormalities in CBC values or the serum biochemical profile were not found in any cat during treatment. However, all ketoconazole-treated cats became anorectic and lost weight. Side effects were not seen in itraconazole-treated cats. During the 3-month posttreatment observation period, all cats remained healthy. At necropsy, histologic evidence of cryptococcosis was not found in the 3 ketoconazole-treated cats or in 2 of the itraconazole-treated cats. In the third itraconazole-treated cat, cryptococcal organisms were found in the kidneys.  相似文献   

5.
A 12-year-old 4-kg spayed domestic shorthair cat with a poorly differentiated fibrosarcoma of the rostral aspect of the mandible and an 11-year-old 13-kg castrated dog of mixed breeding with pulmonary metastatic hemangiosarcoma were treated with 0.5 mg of vincristine sulfate/m2 of body surface, IV, weekly. Three months after beginning treatment, both animals had complete clinical remission. The role of this vinca alkaloid as a single agent for malignant neoplasms has seldom been discussed in the veterinary scientific literature. The results of these two cases indicate that single-agent vincristine sulfate chemotherapy is effective in the treatment of feline fibrosarcoma and canine hemangiosarcoma.  相似文献   

6.
ObservationsA 12 year old cat was presented for anaesthesia to remove a mandibular squamous cell carcinoma. After intramuscular premedication with dexmedetomidine and methadone, anaesthesia was induced with alfaxalone, administered intravenously (IV) to effect, and maintained with isoflurane vaporized in oxygen, following oro-tracheal intubation. Approximately 5 minutes after performing a mandibular nerve block with 1.16 mg kg?1 of bupivacaine, the cat developed severe cardiovascular depression. Anaesthetic delivery was discontinued and cardiopulmonary resuscitation instituted. Drug administration consisted of atropine (0.02 mg kg?1 IV, repeated three times), followed by atipamezole (0.08 mg kg?1 IV). Dobutamine was subsequently administered (1 μg kg?1 minute?1 IV) until cardiovascular performance was considered satisfactory. During recovery from anaesthesia the cat exhibited seizure-like activity, which was controlled by a variable rate infusion of propofol. The cat made an uneventful recovery following discontinuation of propofol infusion, without residual neurological signs, and the surgical procedure was postponed.ConclusionsThis clinical report describes successful management of cardiovascular and neurological complications following a mandibular nerve block with bupivacaine in a cat. Although treatment was successful, the role played by the drugs administered during resuscitation remains uncertain.  相似文献   

7.
CASE DESCRIPTION: An 8-year-old domestic shorthair cat was evaluated because of signs of depression, circling, and visual deficits. CLINICAL FINDINGS: The cat had no cutaneous lesions, and results of an ophthalmologic examination and thoracic radiography were within reference limits. Computed tomography of the brain revealed a mass lesion involving the right parietal, temporal, and occipital lobes; the mass was in broad-based contact with the skull and smoothly marginated and had strong homogenous enhancement after contrast agent administration. During craniectomy, samples of the mass were collected for cytologic and histopathologic evaluations and microbial culture. A diagnosis of Blastomyces dermatitidis-associated meningoencephalitis with secondary pyogranulomatous inflammation was made. TREATMENT AND OUTCOME: Amphotericin B (0.25 mg/kg [0.11 mg/lb], IV) was administered on alternate days (cumulative dose, 1.75 mg/kg [0.8 mg/lb]). To minimize the risk of nephrotoxicosis, assessments of serum biochemical variables (urea nitrogen and creatinine concentrations) and urinalyses were performed at intervals. The third dose of amphotericin B was postponed 48 hours because the cat became azotemic. The cat subsequently received fluconazole (10 mg/kg [4.5 mg/lb], PO, q 12 h) for 5.5 months. Six months after discontinuation of that treatment, the cat appeared healthy and had no signs of relapse. CLINICAL RELEVANCE: Brain infection with B dermatitidis is typically associated with widespread disseminated disease. The cat of this report had no evidence of systemic disease. Blastomycosis of the CNS should be considered as a differential diagnosis for brain lesions in cats from areas in which B dermatitidis is endemic.  相似文献   

8.
Assessment of laryngeal relaxation and ease of intubation in cats was made after preanesthetic medication with acepromazine/meperidine/atropine (IM) and induction of anesthesia 20 minutes later by thiopental administration (IV). Healthy cats (n = 32) scheduled for elective surgery were randomly assigned to 1 of 4 treatment groups to be provided with laryngeal desensitization: group 1, 2% lidocaine HCl (2 mg/kg of body weight) given IV 30 seconds before thiopental induction; group 2, 2% lidocaine HCl (2 mg/kg) topically applied to the larynx; group 3, 10% lidocaine HCl (10 mg) as a topical aerosol; and group 4, no treatment before intubation. A significant (P less than 0.05; ANOVA) difference between groups in the reaction to intubation attempts was apparent. Cats receiving 2% lidocaine IV or no treatment for desensitization had a greater response to intubation than did those receiving 2% or 10% lidocaine topically. The number of attempts required to intubate cats was significantly (P less than 0.05) greater in cats with no treatment than in cats treated topically with 2% or 10% lidocaine. Response to IV administration of 2% lidocaine HCl was not significantly different from the response to other treatments, indicating little advantage over no laryngeal desensitization. It was concluded that topical application of 2% lidocaine (2 mg/kg) or 10% lidocaine aerosol 1 1/2 minutes before intubation provides effective laryngeal desensitization in the cat.  相似文献   

9.
OBJECTIVE: To determine clinical activity and toxic effects of ifosfamide when used to treat cats with vaccine-associated sarcoma (VAS). ANIMALS: 27 cats with a nonresectable, recurrent, or metastatic VAS. PROCEDURE: Each cat received ifosfamide (900 mg/m(2) of body surface area) as an IV infusion during a 30-minute period. Diuresis by infusion of saline (0.9% NaCl) solution and administration of mesna were used to prevent urothelial toxicosis. Treatments were administered every 3 weeks, and tumor response was assessed after the second treatment. All ifosfamide-associated toxic effects were graded in accordance with predetermined criteria. RESULTS: 61 treatments were administered to 27 cats (median, 2 treatments/cat; range, 1 to 4 treatments/cat). After ifosfamide treatment, 1 cat had a complete response and 10 had partial responses for an overall response rate of 11 of 27 (41%; 95% confidence interval [CI], 25% to 59%). Responses lasted from 21 to 133 days (median, 70 days; 95% CI, 60 to 113 days). The acute dose-limiting toxicosis was neutropenia, which was detected 5 to 28 days (median, 7 days) after treatment. Median nadir neutrophil count was 1,600 cells/muL (range, 200 to 5,382 cells/microL). Nine (33%) cats had adverse gastrointestinal effects (primarily salivation during the ifosfamide infusion and inappetence after treatment). Two cats were euthanatized because of severe nephrotoxicosis, and 1 cat developed pulmonary edema during diuresis. CONCLUSIONS AND CLINICAL RELEVANCE: Ifosfamide has antitumor activity against VAS in cats and is tolerated well by most cats. Ifosfamide should be evaluated as an adjuvant treatment for cats with VAS.  相似文献   

10.
Twenty cats with spontaneously arising tumors received oral lomustine at a dose range of 32 to 59 mg/m2 every 21 days. Due to biohazard concerns associated with lomustine capsule reformulation, a standardized 10-mg capsule dosage was used for all cats regardless of body weight. Severe hematological toxicity was infrequent, with the incidence of either grade III or IV neutropenia and thrombocytopenia being 4.1% and 1.0%, respectively. Cats receiving higher cumulative doses of lomustine trended toward a greater likelihood for progressive neutropenia (P=0.07). Two cats with lymphoma, two cats with fibrosarcoma, and one cat with multiple myeloma achieved a measurable partial response to lomustine therapy. Cats treated with higher dosages of lomustine trended toward statistically significant higher response rates (P=0.07).  相似文献   

11.
A 12-year-old neutered male oriental shorthair cat was referred to the Animal Health Trust for investigation of pleural effusion. Ultrasonography revealed marked irregular thickening of the pleural surface of the cranial and caudal mediastinum. Cytological examination of the pleural fluid and fine needle aspirates of the thickened pleura suggested a diagnosis of mesothelioma. Following complete drainage of the thoracic cavity under ultrasound guidance, 180 mg/m2 carboplatin diluted in 60 ml sterile water was infused into the pleural space (30 ml in each hemithorax). This resulted in complete resolution of clinical signs for 34 days (having required thoracocentesis on four occasions in the preceding 4 weeks). The procedure was repeated using 200 mg/m2 carboplatin, and there was a further 20-day period where the cat was free of clinical signs. Further treatment was declined and the cat was euthanased 120 days after initial presentation. This is the first report of successful palliative chemotherapy for suspected feline mesothelioma and suggests that intracavitary carboplatin could be considered in tumours affecting the pleural cavity.  相似文献   

12.
We conducted a clinical evaluation of gemcitabine in 19 dogs with spontaneously occurring malignancies. The principal objectives of this study were to characterize toxicity and seek preliminary evidence of antitumor activity of gemcitabine administered every 2 weeks (biweekly) as a 30-minute IV infusion. A total of 64 doses, ranging from 300 mg/m2 to 675 mg/m2, were administered during the initial 8-week evaluation period, and an additional 131 doses were administered during the extended evaluation period. The total cumulative dose for the 10 dogs receiving gemcitabine in the extended evaluation period ranged from 1,500 mg/m2 to 24,300 mg/m2. Clinical evidence of toxicity was minimal. Cumulative myelosuppression was not apparent. Unexplained retinal hemorrhages occurred in 1 dog. No complete or partial remissions were observed during the initial evaluation period; however, objective responses were observed in 2 dogs during the extended evaluation period. Gemcitabine is a promising new chemotherapeutic agent that can be used safely in dogs with cancer. Biweekly administration of doses of 675 mg/m2 IV results in minimal and acceptable toxicity.  相似文献   

13.
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14.
Hypercalcemia (12.0 to 18.3 mg/dl) was detected in 3 cats that had eaten a rodenticide that contained cholecalciferol. Clinical signs included lethargy, anorexia, vomiting, and polydipsia. Treatment with furosemide and fluids administered IV resulted in normalization of the serum calcium concentration and in remission of the clinical signs in 2 cats. One cat with a serum calcium concentration of 18.3 mg/dl did not have clinical signs, was not treated, and was reportedly normal 9 months after initial examination. We attributed the uniformly favorable outcome of exposure to the rodenticide in these cats to the small quantity of the toxin ingested.  相似文献   

15.
The medical records of 7 hypercalcemic cats with primary hyperparathyroidism were evaluated. Mean age was 12.9 years, with ages ranging from 8 to 15 years; 5 were female; 5 were Siamese, and 2 were of mixed breed. The most common clinical signs detected by owners were anorexia and lethargy. A cervical mass was palpable in 4 cats. Serum calcium concentrations were 11.1 to 22.8 mg/dl, with a mean of 15.8 mg/dl calculated from each cat's highest preoperative value. The serum phosphorus concentration was low in 2 cats, within reference limits in 4, and slightly high in 1 cat. The BUN concentration was greater than 60 mg/dl in 2 cats, 31 to 35 mg/dl in 2 cats, and less than 30 mg/dl in 3 cats. Abnormalities were detected in serum alanine transaminase, aspartate transaminase, and alkaline phosphatase activities from 2 or 3 cats. Parathormone (PTH) concentrations were measured in 2 cats before and after surgery. The preoperative PTH concentration was within reference limits in 1 cat and was high in 1 cat. The PTH concentrations were lower after surgery in both cats tested. A solitary parathyroid adenoma was surgically removed from 5 cats, bilateral parathyroid cystadenomas were surgically resected in 1 cat, and a parathyroid carcinoma was diagnosed at necropsy in 1 cat. None of the cats had clinical problems with hypocalcemia after surgery, although 2 cats developed hypocalcemia without tetany, one of which was controlled with oral administration of dihydrotachysterol and the other with oral administration of 1,25 dihydroxyvitamin D. All 5 of the cta that underwent removal of an adenoma were alive at least 240 days after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

16.
OBJECTIVE: To evaluate the use of the anesthetic combination tiletamine, zolazepam, ketamine, and xylazine (TKX) for anesthesia of feral cats at large-scale neutering clinics. DESIGN: Original study. ANIMALS: 7,502 feral cats. PROCEDURE: Cats were trapped by their caretakers for a feral cat neutering program from July 1996 to August 2000. The anesthetic combination TKX was injected IM into cats while they remained in their traps. Each milliliter of TKX contained 50 mg of tiletamine, 50 mg of zolazepam, 80 mg of ketamine, and 20 mg of xylazine. Females were spayed by veterinarians, whereas males were castrated by veterinarians or veterinary students. Yohimbine (0.5 mg, IV) was administered at the end of the procedure. Logs were kept of the individual drug doses, signalment of the cats, and any complications encountered. These data were analyzed retrospectively (1996 to 1999) and prospectively (2000). RESULTS: Of the 5,766 cats for which dosing records were complete, 4,584 (79.5%) received a single dose of TKX. The mean initial dose of TKX was 0.24 +/- 0.04 ml/cat, and the total mean dose of TKX was 0.27 +/- 0.09 ml. Overall mortality rate was 0.35% (26/7,502) cats, and the death rate attributable solely to potential anesthetic deaths was 0.23% (17/7,502) cats. CONCLUSIONS AND CLINICAL RELEVANCE: The use of TKX for large-scale feral cat neutering clinics has several benefits. The TKX combination is inexpensive, provides predictable results, can be administered quickly and easily in a small volume, and is associated with a low mortality rate in feral cats.  相似文献   

17.
A cat was presented with severe progressive anemia despite marked erythroblastosis. The cat was negative for feline leukemia virus antigen and feline immunodeficiency virus antibody. Bone marrow cytology revealed an excess of erythroid cells with a predominance of prorubricytes and basophilic rubricytes. No response to immunosuppressive therapy was obtained, and a tentative diagnosis of myelodysplastic syndrome was made. The cat showed a partial response to low-dose cytarabine (20 mg/m(2) subcutaneously q24) but died 51 days after the 1st admission. Histopathological examination revealed fibrosis in the bone marrow and marked infiltration of erythroid cells into other organs.  相似文献   

18.
Twenty-eight dogs with lymphoma were treated with a 12-week, 5-drug chemotherapy protocol concluding with high-dose cyclophosphamide supported by autologous bone marrow transplants. A dose escalation design was used to determine the maximum tolerated cyclophosphamide dose (MTD) in this setting. Three cyclophosphamide dose levels were given: 300 mg/ m2 IV (groupl, 3 dogs), 400 mg/m2 IV (group 2, 12 dogs), and 500 mg/m2 IV (group 3, 13 dogs); and the MTD was 500 mg/m2 IV. Toxicity was common but mild, and the dose-limiting toxicity was myelosuppression, specifically neutropenia. No dog died as a result of treatment-related toxicity. One dog in group 3 developed fever, neutropenia, and presumed sepsis and responded promptly to routine management. No other dog required hospitalization. Lower stage and higher cyclophosphamide dose (both increasing dose [study groups 1-3], and the highest dose [group 3]) compared with the lower doses combined (groups 1 and 2) were significantly associated with longer remission duration (all P < .0001). Median remission duration for dogs in group 3 was 54 weeks, compared with 21 weeks for dogs in groups 1 and 2 combined. Factors associated with longer survival time were lower stage (P = .042) and higher cyclophosphamide dose (both increasing dose [study groups 1-3], and the highest dose [group 3] compared with the lower doses combined [groups 1 and 2]) (P = .027). Median survival time for dogs in group 3 was 139 weeks, compared with 43 weeks and 68 weeks for dogs in groups 1 and 2, respectively.  相似文献   

19.
An investigation was initiated to determine the dosage of streptokinase (given IV) that would consistently produce systemic fibrinolysis, as determined by laboratory evaluation, and to determine the relative safety of this drug in the cat. Results indicated that a loading dose of 90,000 IU of streptokinase (given by continuous infusion over 20 to 30 minutes) and a maintenance dosage (IV) of 45,000 IU of streptokinase/hr predictably produced systemic fibrinolysis in the cat. There were no detectable adverse affects seen on physical examination, necropsy, or histopathologic examination. Using the foregoing dosage regimen, investigation was begun to evaluate the use of streptokinase for treatment of feline thromboembolism. Aortic thrombosis was created experimentally in 15 cats. There was no clearly predictable improvement in nonspecific venous angiograms or thermal circulatory indices for the cats given streptokinase, compared with the values for the control cats. After a total of 180 minutes of treatment, the mean weight of remaining clot removed at necropsy from the aortic trifurcation was 7.3 mg in the streptokinase-treated cats, compared with 13.4 mg in the control cats.  相似文献   

20.
OBJECTIVE: To evaluate diagnostic testing that could be used to establish an early diagnosis of cardiotoxicosis induced by long-term administration of doxorubicin. ANIMALS: 13 adult mixed-breed dogs. Procedures-7 dogs were administered doxorubicin chloride (30 mg/m(2), IV, q 21 d for 168 days [cumulative dose, 240 mg/m(2)]), and 6 dogs received saline (0.9% NaCl) solution (5 mL, IV, q 21 d for 168 days; control group). Echocardiography, ECG, arterial blood pressure, plasma renin activity (PRA), and plasma concentrations of norepinephrine and brain natriuretic peptide (BNP) were assessed before each subsequent administration of doxorubicin and saline solution. RESULTS: Dogs that received doxorubicin had a significant decrease in R-wave amplitude, compared with values for the control group, from 30 to 210 mg/m(2). Doxorubicin-treated dogs had decreases in fractional shortening and left ventricular ejection fraction evident as early as 30 mg/m(2), but significant differences between groups were not detected until 90 mg/m(2)was reached. There was also a significant increase in PRA (>or= 120 mg/m(2)) and left ventricular end-systolic and end-diastolic dimensions (>or= 60 and >or= 180 mg/m(2), respectively). Systemic arterial pressure, remaining echocardiographic variables, and concentrations of norepinephrine and BNP had significant variations, but of no clinical importance, during doxorubicin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Doxorubicininduced cardiotoxicosis developed at 120 mg/m(2), but there were no clinical signs of dilated cardiomyopathy or congestive heart failure. Echocardiography and determination of PRA were able to detect early cardiac alterations during the development of dilated cardiomyopathy, despite apparently differing degrees of sensitivity to development of doxorubicin-induced cardiotoxicosis.  相似文献   

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