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Comparison of two formulations of oxytetracycline given prophylactically to reduce the incidence of bovine respiratory disease in feedlot calves

P. Timothy Guichon, Calvin W. Booker, G. Kee Jim

Abstract
A trial involving 1,803 feedlot calves was conducted under commercial feedlot conditions in western Canada to compare the relative effectiveness of a new oxytetracycline formulation, administered either intramuscularly (BMI) or subcutaneously (BMS), to a currently available oxytetracycline formulation, administered intramuscularly (LAB), for the prevention of bovine respiratory disease (BRD) in feedlot calves. All experimental treatments were administered upon arrival at the feedlot and again on the third day after arrival. Over the entire feeding period, there were no significant differences (p20.05) in the BRD treatment rates or the BRD relapse rates between either the BMI or BMS groups compared to the LAB group. Similarly, there were no significant differences (p20.05) in the BRD treatment rates in the BMI or BMS groups from days 8-14, days 15-90, or days 1-90 of the feeding period compared to the LAB group. However, during the first seven days of the feeding period the BRD treatment rate in the BMI group was 1.55 times (p<0.05) higher than in the LAB group. From days 1-90 and day 1 to the end of the feeding period, the overall mortality rates, BRD mortality rates, and BRD case fatality rates were two to six times lower in the BMS and BMI groups as compared to the LAB group; however, these differences were not statistically significant (p20.05). These data indicate that both the intramuscular and subcutaneous administration of a new oxytetracycline formulation are comparable to the intramuscular administration of a currently available oxytetracycline formulation when given to calves upon arrival at the feedlot.
Resume

les veaux au parc d'engraissement. La nouvelle presentation a ete comparee a l'ancienne administree par voie intramusculaire (AIM). Tous les traitements ont ete administres au jour meme de l'arrivee des animaux au parc d'engraissement et au troisieme jour. Durant toute la periode de croissance, il n'y avait pas de difference significative (p 2 0,05) dans la frequence des traitements pour MRB ou concernant les taux de rechute entre les groupes ayant requ la nouvelle forme pharmaceutique par voies intramusculaire ou sous-cutanee et le groupe recevant l'ancienne presentation. De meme, il n'y avait pas de difference significative (p 2 0,05) dans la frequence des traitements pour MRB pour les groupes NIM et NSC comparativement au groupe AIM pour les periodes entre 8-14 jours, 15-90 jours et 1-90 jours. Toutefois, durant les sept premiers jours de la periode d'observation, la frequence des traitements pour les MRB pour le groupe NIM etait 1,55 fois plus elevee que pour le groupe AIM. Pour les periodes de 1-90 jours et du jour 1 jusqu'a l'abattoir, le taux global de mortalite, le taux de mortalite relie aux MRB et le taux de morbidite des MRB etaient de deux a six fois plus bas pour les groupes NIM et NSC comparativement au groupe AIM; toutefois, ces differences ne'etaient pas statistiquement significatives (p .0,05). Ces donnees montrent que l'efficacite de l'administration par voies intramusculaire ou sous-cutanee de la nouvelle forme pharmaceutique d'oxytetracycline est comparable a celle de l'administration par voie intramusculaire de la preparation presentement disponible d'oxytetracycline chez les veaux traites lors de leur arrivee au parc d'engraissement.
(Traduit par Dr Thirkse Lanthier)
Can Vet J 1993; 34: 736-741

Comparaison entre deux formes pharmaceutiques d'oxytetracycline administrees en prophylaxie pour diminuer l'incidence des maladies respiratoires bovines chez les veaux gardes au parc d'engraissement L'etude s'est deroulee dans des parcs commerciaux d'engraissement de l'Ouest canadien et comptait 1803 veaux. Elle consistait 'a determiner l'efficacite relative d'une nouvelle forme pharmaceutique d'oxytetracycline administree par voies intramusculaire (NIM) ou sous-cutanee (NSC) pour la prevention des maladies respiratoires bovines (MRB) chez
Feedlot Health Management Services, Postal Bag Service 5, 7-87 Elizabeth Street, Okotoks, Alberta TOL lTO.

Introduction
n western Canada, bovine respiratory disease (BRD) continues to be an economically important disease entity in the feedlot (1-3). In the past several years, beef feedlots have become more sophisticated in managing health problems associated with this disease complex. The usefulness of administering prophylactic antibiotics to stressed calves upon arrival at the feedlot has been widely reported (4-9). Studies have documented reductions in BRD treatment days (4,5), BRD morbidity (6,7), and BRD mortality (8). A recent western Canadian study (9) showed that two different oxytetracycline products given to calves upon arrival at the feedlot reduced the subsequent BRD morbidity during the first two weeks on feed and for the entire feeding period by 15%-19% (p<0.05). Moreover,
Can Vet J Volume 34, December 1993

This project was wholly supported by a research grant from Boehringer Ingelheim (Canada) Ltd.
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25

Table 1. Formulas for the calculation of various percentage risks and relative risk
BRDa treatment
= (# of calves treated for the initial episode of BRD during a time period divided by # of calves untreated for BRD x 100% prior to the time period)

20

First BRD relapse

= (# of first BRD relapses divided by the total number of calves initially treated x 100% for BRD) = (# of mortalities due to all causes divided by the total number of calves)
= (# of BRD attributable mortalities divided by the total number of calves) = (# of mortalities in calves treated for BRD divided by the total number of calves treated for BRD) = risk for the experimental group (BMlb or BMSC) divided by the risk for the positive control group (LABd)

10 12 14 16 18 20 22 24 26 28 Dp on Foo

Overall mortality
BRD mortality BRD case

Figure 1. Distribution of new bovine respiratory disease (BRD) cases by days on feed. BMI = prophylactic intramuscular oxytetracycline at the rate of 20 mg/kg body weight (BW) (Biomycin 200, Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario). BMS = prophylactic subcutaneous oxytetracycline at the rate of 20 mg/kg BW (Biomycin 200, Boehringer Ingelheim (Canada) Ltd.) LAB = prophylactic intramuscular oxytetracycline at the rate of 20 mg/kg BW (Liquamycin LA, rogar/STB, Pointe Claire-Dorval, Quebec).
one

x 100%

x 100%

fatality

x 100%

Relative risk

of these oxytetracycline products reduced the overall mortality rate for the entire feeding period by 44%

(p<O.05).
The purpose of the study reported herein was to comunder commercial feedlot conditions, the relative effectiveness of a new oxytetracycline formulation (Biomycin 200, Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario) to a currently available oxytetracycline formulation (Liquamycin LA, rogar/STB, Pointe Claire-Dorval, Quebec) when given to calves upon arrival at the feedlot.
pare,

aBovine respiratory disease (BRD) bProphylactic intramuscular oxytetracycline at the rate of 20 mg/kg body weight (BW) (Biomycin 200, Boehringer Ingelheim (Canada) Ltd, Burlington, Ontario) cProphylactic subcutaneous oxytetracycline at the rate of 20 mg/kg BW (Biomycin 200, Boehringer Ingelheim (Canada) Ltd.) dProphylactic intramuscular oxytetracycline at the rate of 20 mg/kg BW (Liquamycin LA, rogar/STB, Pointe ClaireDorval, Quebec)

Materials and methods


Trial facilities The trial was conducted in a commercial feedlot near Strathmore, Alberta, which has a capacity of 22,000 animals. The basic design of this feedlot is representative of standard design in western Canada. The calves were housed in open air, dirt floor pens arranged side by side with a central feed alley and a 10% porosity fence. Each pen measured 50 X 80 meters. There were approximately 305 calves per pen. There are two hospital facilities located in the feedlot. Each hospital has covered shelter for 100 animals, a hydraulic chute equipped with an individual animal scale, a chute-side computer for animal health data, and separation alleys to facilitate the return of cattle to designated pens. Three open air hospital pens are located adjacent to each hospital. Also, there are six receiving pens and an enclosed processing facility.
Trial animals The animals utilized in the study were recently weaned, crossbred beef steer and bull calves purchased from auction markets throughout western Canada. Approximately 75 calves per truck were transported to the feedCan Vet J Volume 34, December 1993
December

lot after assembly at the auction market. The calves were 7-10 months of age and weighed approximately 250-370 kg. Upon arrival at the feedlot, the calves were moved through a hydraulic chute for a group of procedures known collectively as processing. All animals were ear tagged (to provide unique, individual animal identification), given an injection of vitamins A and D (Poten AD, rogar/STB), implanted with a progesterone-estradiol implant (Steer-oid, Boehringer Ingelheim (Canada) Ltd.), and vaccinated against infectious bovine rhinotracheitis (IBR) and parainfluenza-3 (PI3) viruses (IBR-PI3, Coopers Agropharm Inc., Ajax, Ontario). In addition, each animal received a multivalent clostridial and Haemophilus somnus vaccine (Fermicon 7, Boehringer Ingelheim (Canada) Ltd.), a Pasteurella haemolytica bacterial extract (Presponse, Langford Inc., Guelph, Ontario), and topical ivermectin (0.5%) at the rate of 1.0 mL/10 kg body weight (BW) (Ivomec Pour On, MSD Agvet, Kirkland, Quebec). At approximately day 90 of the feeding period for a pen, all animals in the pen were reimplanted (Steer-oid, Boehringer Ingelheim (Canada) Ltd.), revaccinated against IBR and PI3 viruses (IBRJPI3, Coopers Agropharm Inc.), and the bulls were castrated.
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Table 2. Various disease risks (%) for each group by days on feed when first treated
Days on
feed
BRD treatmenta
1-7 8-14 15-90 1-90 I -end

BMIf
10.63 15.24 14.69 35.58 36.05

BMS9
8.64 11.27 12.30 28.90 29.57

LABh
6.84 14.70 15.34 32.72 33.06

Average
8.71 13.73 14.08 32.34 32.89 22.64 23.78 1.39 1.77

First BRD relapseb 1-90 1-end

25.35 25.81 1.16 1.33


0.17 0.17

20.11 22.47
0.83 1.33
0.17 0.33

21.94 22.73
2.17 2.67 0.83 1.00 5.61 6.06

Overall mortalityc
BRD mortalityd
BRD case fatalitye

1-90 1-end 1-90 1 -end 1-90 I-end

0.39 0.50
3.43 3.88

2.82 3.23

1.75 2.25

alnitial treatment for bovine respiratory disease (BRD)


dMortality attributable to BRD eMortality in calves treated for BRD fProphylactic intramuscular oxytetracycline at the rate of 20 mg/kg body weight (BW) (Biomycin 200, Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario) gProphylactic subcutaneous oxytetracycline at the rate of 20 mg/kg BW (Biomycin 200, Boehringer Ingelheim (Canada) Ltd.) hProphylactic intramuscular oxytetracycline at the rate of 20 mg/kg BW (Liquamycin LA, rogar/STB, Pointe Claire-Dorval, Quebec)

CMortality due to all causes

bCalves treated for BRD that relapsed

Experimental design pen. Note that the treatment groups were commingled in Based on the historical occurrence of BRD in auction these pens. market derived feedlot calves (unpublished observaOn the third day after arrival at the feedlot, the initial tions), it was anticipated that the new oxytetracycline for- oxytetracycline injection sites were clinically examined. mulation would decrease the subsequent BRD treat- Reactions were categorized and recorded as follows: ment rate from 35% to 25%. Conditional on at least a SO (no reaction); SI (small swelling up to 5 cm diame90% chance of detecting a decrease as large as this or ter); S2 (mild swelling 5-10 cm diameter); S3 (moderlarger and a 95% certainty that this difference was not ate swelling 10-15 cm diameter); or S4 (severe swelling due to chance, approximately 600 animals per treat- >15 cm diameter). Also, all calves received a second ment group would be required. Including 600 animals per oxytetracycline injection. The same product was used at treatment group resulted in powers to detect 50% reduc- the same dosage level and route of administration as at tions in BRD case fatality and overall mortality rates of initial processing. In addition, rectal temperature was approximately 70% and 50%, respectively. recorded; however, no assessment of "sickness" was Upon arrival at the feedlot, each truckload was des- made at this time. Thereafter, the entire processing ignated as a processing group. During the processing pro- group was placed in a designated feedlot pen. Additional cedures, the weight and rectal temperature of each calf processing groups were added to the pen following the was recorded and calves with an elevated body temsame procedure outlined above until the pen contained perature (240.0C) were excluded from the trial. The approximately 305 calves. In this study, it took from two remaining calves were assigned on a random basis to one to six days to fill a pen. of three treatment groups as follows: BMI, which Exsactly 1803 animals were placed on the trial and received intramuscular oxytetracycline at the rate of housed in six pens. There were 602 calves allocated 20 mg/kg BW (Biomycin 200, Boehringer Ingelheim to the BMI group, 602 calves allocated to the BMS (Canada) Ltd.); BMS, which received subcutaneous group, and 599 calves allocated to the LAB group. The oxytetracycline at the rate of 20 mg/kg BW (Biomycin trial commenced on November 6, 1991 and was com200, Boehringer Ingelheim (Canada) Ltd.); or LAB, pleted on June 7, 1992, when the last animals were which received intramuscular oxytetracycline at the sent to slaughter. rate of 20 mg/kg BW (Liquamycin LA, rogar/STB). Injections were administered in the neck region just in Animal health front of the shoulder and no more than 20 mL of prod- The cattle were observed once or twice daily by expeuct were injected per site. After processing, the entire rienced pencheckers. The treatment status of each anigroup of animals was placed in a designated arrival mal was unknown to the pencheckers. Cattle deemed to Can 738 Can Vet Vet J J Volume Volume 34, December 1993 1993 34, December

Table 3. Relative risks for BRD treatment and BRD relapse


Days on feed

Relative risk 1.55 1.04 0.96 1.08 1.09 1.26 0.77 0.80 0.88 0.89

95%

CIe
2.26 1.38 1.30 1.27 1.27 1.87 1.04 1.10 1.05 1.06 1.64 1.60 1.36 1.44

BRD treatmenta BMIC

1-7 8-14 15-90 1-90 1 -end 1-7 8-14 15-90 1-90 1-end
1-90 1-end

1.07 0.78 0.71 0.92 0.93 0.85 0.56 0.58 0.75 0.76 0.81 0.81 0.62 0.68

0.020 0.800 0.784 0.331 0.276 0.245 0.090 0.171 0.152 0.193 0.418 0.465 0.668 0.953

BMSd

First BRD relapseh BMIC

1.16 1.14
0.92 0.99

BMSd

1-90 1 -end

alnitial treatment for bovine respiratory disease (BRD) bCalves treated for BRD that relapsed CProphylactic intramuscular oxytetracycline at the rate of 20 mg/kg body weight (BW) (Biomycin 200, Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario) dProphylactic subcutaneous oxytetracycline at the rate of 20 mg/kg BW (Biomycin 200, Boehringer Ingelheim (Canada) Ltd.) ePrecision based 95% confidence intervals for relative risk
be "sick" by the pencheckers were taken to the hospital facility, diagnosed, and treated as per written treatment protocols provided by the consulting veterinarians. In the study reported herein, the case definition for bovine respiratory disease (BRD) was an elevated rectal temperature (240.3C) and a lack of abnormal clinical signs referable to organ systems other than the respiratory system. The treatment events, including the treatment date, presumptive diagnosis, drug(s) used, and dosage used, were recorded on the chute-side computer
system.
rate (mortality due to all causes), the BRD mortality rate (mortality attributable to BRD), and the BRD case fatality rate (mortality in calves treated for BRD) were calculated for each treatment group for the intervals days 1-90 and day I to the end of the feeding period

Subsequent to the initial treatment episode, a BRD relapse was defined as an animal selected by the pencheckers as "sick", having a rectal temperature 240.0C, with no abnormal clinical signs referable to organ systems other than the respiratory system. Bovine respiratory disease relapses were treated as per written treatment protocols for such cases. The treatment events were recorded on the chute-side computer system as outlined above. All dead animals were necropsied by the attending feedlot veterinarians. If the cause of death could not be ascertained by gross postmortem examination, tissues were submitted to the Regional Veterinary Diagnostic Laboratory in Airdrie, Alberta, to aid in determining the cause of death. Data collection and management Health summaries for each treatment group, up to and including the last day of the feeding period, were printed from the mainframe computer at the feedlot. From these data, risk rates for initial treatment for BRD for the intervals: days 1-7; days 8-14; days 15-90; days 1-90; and day I to the end of the feeding period were calculated for each treatment group. The BRD relapse rate (calves treated for BRD that relapsed), the overall mortality
Can Vet J Volume 34, December 1993

(Table 1). The injection site scores were summarized for each experimental group. The proportion of calves in each group exhibiting evidence of injection site swelling was calculated. The distribution of new BRD cases in each treatment group by the number of days on feed was plotted graphically for the first 28 days of the feeding period. Statistical analysis The BMI and BMS treatment groups were compared to the LAB group. For the various animal health indices defined in the previous section, relative risks (RR) and their 95% confidence intervals (95% CI) were calculated for the BMI and BMS groups using the precision based technique (10). Chi-square tests of association, without correction for continuity, were calculated for each RR (1 1). In cases when the expected values were less than five, Fisher's Exact two-tailed test was used (12).

Results
At processing, a total of 30 calves (1.6%) had an elevated body temperature (240.0C) and were excluded from the trial. Eighty-eight percent of the animals in the BMS group exhibited evidence of subcutaneous swelling at the time of the second oxytetracycline injection. Conversely, less than 2% of the animals in the BMI and LAB groups had similar reactions. The distribution of new BRD cases in each treatment group by the number of days on feed is shown in
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Table 4. Relative risks for mortality and BRD case fatality


Days on feed Relative risk 95%

CIf
1.33 1.15 1.07 1.15 1.70 1.37
1.70 1.64

Overall mortalitya BMId


BMSc
BRD mortalityb BMId

1-90 1 -end 1-90 1-end

0.54 0.50 0.38 0.50


0.20 0.17 0.20 0.33 0.50 0.53 0.31 0.37

0.22 0.21
0.14 0.21 0.02 0.02 0.02 0.07 0.19 0.21 0.09 0.12

0.172 0.097 0.056 0.097


0.123 0.057

1-90 1-end
I-90 1 -end
1-90 1-end 1-90 1 -end

BMSe BRD case fatalityc BMId

0.123 0.154 0.157 0.168 0.050 0.067

1.33 1.33
1.08 1.13

BMSC

aMortality due to all causes bMortality attributable to bovine respiratory disease (BRD) CMortality in calves treated for BRD dProphylactic intramuscular oxytetracycline at the rate of 20 mg/kg body weight (BW) (Biomycin 200, Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario) eProphylactic subcutaneous oxytetracycline at the rate of 20 mg/kg BW (Biomycin 200, Boehringer Ingelheim (Canada) Ltd.) fPrecision based 95% confidence intervals for relative risk

Table 5. Cause specific mortality summary


Mortality
Treatment group
BMIa

No. of animals 602 602 599

BRDd
1 2 5

HSe
6 5 8

Misc.f
1 1 3

No. of mortalities
8 8 16

BMS"
LABC

aProphylactic intramuscular oxytetracycline at the rate of 20 mg/kg body weight (BW) (Biomycin 200, Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario) bProphylactic subcutaneous oxytetracycline at the rate of 20 mg/kg BW (Biomycin 200, Boehringer Ingelheim (Canada) Ltd.) cProphylactic intramuscular oxytetracycline at the rate of 20 mg/kg BW (Liquamycin LA, rogar/STB, Pointe Claire-Dorval, Quebec) dMortality attributable to bovine respiratory disease (BRD) cMortality attributable to Hemophilus somnus infection fMortality attributable to miscellaneous causes

Figure 1. The BRD treatment rates, BRD relapse rates, overall mortality rates, BRD mortality rates, and BRD case fatality rates for various intervals of the feeding period are shown in Table 2. The RR and 95% CI for the morbidity and mortality parameters are shown in Tables 3 and 4, respectively.
During
the first
seven

days

of the

feeding period,

the

BRD treatment rate was 1.55 times higher in the BMI group than in the LAB group (p<0.05). However, there were no significant differences (p.0.05) in the BRD treatment rates between the BMI and the LAB treatment group from days 8-14, days 15-90, or days 1-90 of the feeding period. Moreover, during the entire feeding period, there were no significant differences (pO0.05) in the BRD treatment rates or the BRD relapse rates between the BMI and LAB groups (Table 3).
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There were no significant differences (p20.05) in the BRD treatment rates for days 1-7, days 8-14, days 15-90, or days 1-90 of the feeding period between the BMS and LAB treatment groups. In addition, over the entire feeding period, there were no significant differences (p>0.05) in the BRD treatment rates or the BRD relapse rates between the BMS and LAB groups (Table 3). Over the first 90 days of the feeding period, there were no significant differences (p20.05) in the overall mortality rates, the BRD mortality rates, or the BRD case fatality rates between either the BMI or the BMS groups as compared to the LAB group. Similarly, there were no significant differences (p20.05) in the mortality rates between these groups over the entire feeding period. Cause specific mortality for each treatment group is summarized in Table 5.
Can Vet J Volume 34, December 1993

Discussion
The proportion of animals exhibiting subcutaneous swellings in the BMS group was considerably greater than in either the BMI or LAB groups. The most likely explanation for this apparent increase in injection site reactions is the fact that the oxytetracycline in the BMS group was administered subcutaneously as opposed to intramuscularly in the BMI and LAB groups. The injection site scoring system evaluated subcutaneous reactions and not intramuscular inflammation. It should be noted that none of the animals in the study were treated for injection site reactions. A significantly higher proportion of animals in the BMI group were treated for BRD than in the LAB group during the first seven days of the feeding period. The relevance of this observation is unknown. Given the number of multiple comparisons made between these groups and the fact that there were no differences in the BRD treatment rates from days 8-14, days 15-90, days 1-90, or day I to the end of the feeding period between these two groups, it is likely that the difference in BRD treatment rates during the first seven days of the feeding period is due to Type I error. It should be noted that the most important data to consider when making a decision regarding the relative effectiveness of the three experimental groups are the data from day 1 to the end of the feeding period. Moreover, interpretation of interval data, without considering the data obtained over the entire feeding period, is of questionable validity. During the entire feeding period, the overall mortality rate in both the BMI and BMS groups was two times lower than in the LAB group. Similarly, the BRD mortality rate was six times lower in the BMI group and three times lower in the BMS group than in the LAB group. In addition, the BRD case fatality rate was approximately two times lower in both the BMI and BMS groups than in the LAB group. Although none of these differences in mortality are statistically significant (p20.05), the numerical trend always favors the BMI and BMS groups. In a previous study (9), calves derived from auction markets in a scenario similar to those in this study had overall mortality rates of 4.13%-7.3%. The overall mortality rates observed in this study were only 1.33% in both the BMI and BMS groups and 2.67% in the LAB group. As a result of these lower than expected mor-

tality rates, the power of this study to detect differ ences in mortality was reduced.

Acknowledgments
We thank Dr. Paul Doig for technical assistance in conducting this trial. Also, we thank the management and staff of Thiessen Farms Ltd., Strathmore, Alberta, foi their assistance and cooperation. cv.

References
1. Kelly AP. Disease patterns in feedlot cattle. (MSc thesis) Saskatoon, Saskatchewan: University of Saskatchewan, 1984. 2. Church TL, Radostits OM. A retrospective survey of diseases ol feedlot cattle in Alberta. Can Vet J 1981; 22: 27-30. 3. Blood DC, Radostits OM. Veterinary Medicine. 7th ed. London: Bailliere Tindall, 1989: 664. 4. Lofgreen GP. Mass medication in reducing shipping fever bovine respiratory complex in highly stressed calves. J Anim Sci 1983; 56: 529-536. 5. Breeze RG, Magonigle RA, McManus RF, Grimson RE. Control of shipping fever in feedlot cattle with a long-acting oxytetracycline injectable. Bovine Practice 1982; 3: 33-38. 6. Bennett BW, Rupp GP, McCovmick AM. Pre-shipment preventive medication of calves with liquamycin at weaning. AgriPract 1983; 4: 6-10. 7. Janzen ED, McManus RF. Observations on the use of a long-acting oxytetracycline for in-contact prophylaxis of undifferentiated bovine respiratory disease in feedlot steers under Canadian conditions. Bovine Practitioner 1980; 15: 87-90. 8. Albak C, Bradstock L, Cruise L, et al. Prophylactic treatment of feedlot calves at processing with a long-acting oxytetracycline. Bovine Practitioner 1986; 21: 192-194. 9. Harland RJ, Jim GK, Guichon PT, Townsend HGG, Janzen ED. Efficacy of parenteral antibiotics for disease prophylaxis in feedlot calves. Can Vet J 1991; 32: 163-168. 10. Kleinlaum DG, Kupper LL, Morgenstern H. Epidemiological Research. Principles and Quantitative Methods. Belmont, California: Wadsworth, 1982: 351-355. 11. Steel RGD, Torrie JH. Principles and Procedures of Statistics. A Biometrical Approach. 2nd ed. New York: McGraw Hill, 1980: 502. 12. Daniel WW. Biostatistics: A Foundation for Analysis in the Health Sciences. 4th ed. New York: John Wiley and Sons, 1987: 537-552.
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