Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs   总被引：1，自引：1，他引：0  

Rodney L. Page DVM  MS    Margaret C. McEntee DVM    Steven L. George PhD    Patrick L. Williams PhD    Greta L. Heidner DVM    Carol A. Novotney DVM    Jim E. Riviere DVM  PhD    Mark W. Dewhirst DVM  PhD  Donald E. Thrall DVM  PhD 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》1993,7(4):235-240

Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30-minute intravenous infusion in a dose escalation study. Twenty-eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD₅₀) or a 5% incidence of severe toxicity (SEV₅). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD₅₀ and SEV₅ for the first treatment course were 340 and 278 mg/M², respectively. MOD₅₀ and SEV₅ values for the first plus second treatment courses were 327 and 231 mg/M², respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T_1/2), area-under-the-curve and total body clearance (CL_b) were not dose dependent. Volume of distribution (VD_ss) significantly increased with dose only between 100 and 150 mg/M², not between 150 and 300 mg/M². Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.)  相似文献   

Effect of birthweight, total protein, serum IgG and packed cell volume on risk of neonatal diarrhea in calves on two California dairies.   总被引：3，自引：0，他引：3       下载免费PDF全文

J Paré  M C Thurmond  I A Gardner    J P Picanso 《Canadian journal of veterinary research》1993,57(4):241-246

The objective of the study was to determine if there was a relationship between hematological, immunological and physiological variables of newborn calves and risk of diarrhea during the neonatal period. Four hundred and seventeen heifer calves from two dairies (A and B) in the San Joaquin Valley of California were enrolled at birth and scored daily, to 28 days of age, for evidence and severity of diarrhea (0 to 3). Calves were weighted at birth and blood sampled at two to five days of age to determine packed cell volume (PCV), total protein (TP) and IgG serum concentration. The Cox proportional hazards model was used to determine if age at onset of the first diarrhea episode and length of the first episode were associated with the hypothesized variables (PCV, TP, IgG and birthweight). The IgG concentration was not associated with the age at onset of diarrhea (p = 0.6052, Dairy A; p = 0.4393, Dairy B) but a high IgG concentration was associated with a decreased length of episode (p = 0.0325, Dairy A; p = 0.0912, Dairy B), particularly for calves born in the winter on dairy A (p = 0.0211). For calves born in the winter, those with either a high or a low birthweight had diarrhea at a younger age (p = 0.0102, Dairy A; p = 0.0020, Dairy B). Associations were also found for PCV and TP with both the age at onset and length of the first episode of diarrhea. Results suggest that parameters measurable at, or shortly after birth may have important prognostic value in evaluating risk of calf diarrhea.  相似文献   

Efficacy of parenteral antibiotics for disease prophylaxis in feedlot calves   总被引：9，自引：9，他引：0       下载免费PDF全文

Harland RJ  Jim GK  Guichon PT  Townsend HG  Janzen ED 《The Canadian veterinary journal. La revue veterinaire canadienne》1991,32(3):163-168

Trimethoprim-sulfadoxine (TMPSDX) and two formulations of oxytetracycline (OTC) were examined for their prophylactic efficacy in feedlot calves when given by intramuscular injection on arrival at a large commercial feedlot. The study included 2,112 high-risk feeder calves that developed disease early in the feeding period. Both formulations of OTC reduced bovine respiratory disease morbidity during the first two weeks on feed and for the entire feeding period by 15-19% (p<0.05), and they also reduced all fatal fibrinous pneumonia by 67% and 84% (p<0.05). All three drugs significantly reduced all fatal disease in animals first treated during the second week on feed, but not for the overall feeding period. Oxytetracycline with 2-pyrrolidone reduced the incidence of all fatal disease by 44% (p<0.05) during the entire feeding period. The case fatality risk for calves first treated during the second week on feed was lower (p<0.05) in the TMPSDX group and in the OTC with polyvinyl-pyrrolidone group.  相似文献   

Public advertising of Rx drugs - Disagreement with CVMA position          下载免费PDF全文

Jim GK  Guichon PT 《The Canadian veterinary journal. La revue veterinaire canadienne》1991,32(9):519

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The relative economics of feeding open, aborted, pregnant feedlot heifers   总被引：1，自引：1，他引：0       下载免费PDF全文

Jim GK  Ribble CS  Guichon PT  Thorlakson BE 《The Canadian veterinary journal. La revue veterinaire canadienne》1991,32(10):613-617

A 90-day finishing trial involving 144 feedlot heifers was conducted to compare the performance parameters and carcass characteristics of open heifers, therapeutically aborted heifers, and pregnant heifers. In the first 28 days of the trial, the aborted heifers had reduced (p < 0.05) feed intake (FI), average daily gain (ADG), and feed efficiency (FE) compared to pregnant and open heifers. Over the entire trial, on a live weight basis, the aborted group had reduced (p < 0.05) final weight, ADG, and FE compared to pregnant and open heifers. However, when the data were adjusted for total uterine weight, the aborted and open heifers had improved (p < 0.05) final weight, ADG, and FE compared to pregnant heifers. The aborted and open group had a higher (p < 0.05) carcass weight, rib eye area, dressing percentage, and cutability estimate compared to the pregnant heifers. The aborted group had lower (p < 0.05) carcass weight than the open heifers. Over the entire 90-day feeding period, there were no statistically significant differences among the groups with respect to feed intake (FI), average fat, grade fat, and carcass grades. Also, there were no significant health problems or mortality in any of the groups.

In the economic analysis, aborted heifers returned $26.41 per head more than pregnant heifers. Open heifers returned $39.94 per head more than aborted heifers, and $66.35 more than pregnant heifers. Thus, aborting feedlot heifers during the second trimester was determined to be a safe and cost effective management decision.

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The anti-proteolytic activity of blood and ovarian follicular fluid in sheep after stimulation with serum gonadotropin (PMSG) and administration of Antisergon]     

M Molnárová  J Arendarcik  T Mészárosová 《Veterinární medicína》1991,36(8):497-507

The synthesis and secretion of trypsin (trypsin model serine protease) inhibitors are regulated in ovarian follicles by gonadotropins. The superovulation stimulations with 400 IU FSH, 1000 IU PMSG, 1000 IU HCG, 750 IIU PMSG + 750 IU HCG influence in a different way the trypsin inhibiting activities (TIA) of blood plasma (BP) (Figs 1 and 2) and follicular fluid (fig. 3); this points to a possibility of local effects. An increase in the average values of TIA in BP was statistically significant during the whole experiment: P less than 0.05 to P less than 0.001 (following the administration of PMSG+HCG, or PMSG, and HCG); Antisergon administered in 68 hours after PMSG reduced this increase. The changes in the fraction of low-molecular TIA in BP (after BP treatment with perchloric acid) were of converse nature; a decrease in the average values ranged from P less than 0.02 to P less than 0.001 (following PMSG or other stimulations). Antisergon did not influence this decrease. The changes observed on particular days of the trial (Figs. 1 and 2) also indicate different effects of the preparations, mainly of the component LH, which resulted in the occurrence of large nonovulating follicles (greater than 10 mm--"cystic" ones). No such follicles were observed in nonstimulated ewes and after FSH stimulation. The administration of antisergon (goat's antiserum against PMSG) 68 hours after PMSG administration did not prevent their creation. The TIA of follicular fluid (FF) of antral follicles was on average tenfold in comparison with that of blood plasma; and the TIA FF of follicles greater than 10 mm was higher (up to P less than 0.001) than the TIA FF of follicles less than 10 mm. The administration of Antisergon in shorter intervals following PMSG administration (12, 24, 48 and 58 hours) influenced the average values of TIA BP in 120 hours (since PMSG administration) in dependence on time (Tab. I). The effects of Antisergon administered in 12 and 24 hours after PMSG administration on the TIA BP were insignificant if it was administered in 48 and 58 hours the TIA BP increased (P less than 0.02; P less than 0.001) in comparison with the interval of 12 hours. The TIA FF of follicles less than 5 mm, 5-10 mm and greater than 10 mm varied in dependence on the time intervals of Antisergon administration (Fig. 4). The statistical significance of these changes in shown in Tab. II.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

Les fichiers vétérinaires de OPEN ACCESS II          下载免费PDF全文

Léger L 《The Canadian veterinary journal. La revue veterinaire canadienne》1988,29(4):401

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Comparison of penicillin, oxytetracycline, and trimethoprim-sulfadoxine in the treatment of acute undifferentiated bovine respiratory disease   总被引：6，自引：5，他引：1       下载免费PDF全文

Mechor GD  Jim GK  Janzen ED 《The Canadian veterinary journal. La revue veterinaire canadienne》1988,29(5):438-443

Penicillin, oxytetracycline, and a trimethoprimsulfadoxine combination were compared as first choice antibiotics for the treatment of acute bovine respiratory disease in weaned beef calves. There was no statistical difference in the mortality losses due to respiratory disease; however, the case fatality rate in the trimethoprim-sulfadoxine treatment group (3%) was markedly lower than in the penicillin (10%) and oxytetracycline (8%) treatment groups. The trimethoprim-sulfadoxine group also had statistically fewer treatment days compared to the penicillin and oxytetracycline groups (p < 0.05). Inclusion of mortality costs in the calculation of treatment costs demonstrated that treatment of the trimethoprimsulfadoxine group was appreciably less costly than treatment of the other groups. Temperature response abnormalities, defined as either an elevation in temperature or a failure of temperature to drop from one treatment day to the next, were associated with a relapse rate of approximately 50%. In vitro antibiotic sensitivity testing of Pasteurella haemolytica isolated from pretreatment nasal swabs was not a useful predictor of treatment success of antimicrobials.  相似文献   

Fine needle aspiration biopsy of malignant tumors in dogs and cats: a report of 102 cases          下载免费PDF全文

Ménard M  Fontaine M  Morin M 《The Canadian veterinary journal. La revue veterinaire canadienne》1986,27(12):504-510

Fine needle aspiration biopsy is a fast and inexpensive technique well tolerated by animals. Its efficacy for the diagnosis of malignancy and determination of cellular origin was investigated for 97 malignant tumors and five benign lesions in 83 dogs and 19 cats. Histological examination of the lesions was performed in each case. Malignancy was detected by cytology in 69% of the malignant tumors. The cellular origin of the lesion was determined in 74% of the cases. Confirmation of malignancy and determination of cellular origin permitted an early diagnosis and prognosis. Since fine needle aspiration biopsy and cytology cannot definitely rule out malignancy, a surgical biopsy and histopathology should be done when malignancy is suspected clinically and not confirmed cytologically. Specimens of good quality, adequate collaboration between the cytologist and clinicians, and sufficient knowledge of pathology and cytology are basic requirements for obtaining good results with fine needle aspiration biopsy and cytology.  相似文献   

Transitional Cell Carcinoma of the Urinary Bladder in a Beluga Whale (Delphinapterus leucas)   总被引：1，自引：0，他引：1       下载免费PDF全文

Martineau D  Lagacé A  Massé R  Morin M  Béland P 《The Canadian veterinary journal. La revue veterinaire canadienne》1985,26(10):297-302

A transitional cell carcinoma of the urinary bladder was found in a beluga whale stranded in the St. Lawrence middle estuary. Various organs of this animal were submitted to high resolution gas chromatography coupled with mass spectrometry analysis. High frequency of urinary bladder cancer in the human population of the same area and the presence of carcinogenic compounds in the marine environment of this animal are discussed.

Concurrent isolation of Edwardsiella tarda from various organs of this whale is also reported.

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