Characterizing the diagnostic sensitivity and specificity of pain biomarkers in cattle using receiver operating characteristic curves.

Biomarkers are used to assess pain and analgesic drug efficacy in livestock. However, often the diagnostic sensitivity and specificity of these biomarkers for different painful conditions over time have not been described. Receiver operating characteristic (ROC) curves are graphical plots that illustrate the diagnostic ability of a test as its discrimination threshold is varied. The objective of this analysis was to use area under the curve (AUC) values derived from ROC analysis to characterize the predictive value of potential pain biomarkers at specific time points following a painful stimulus. The biomarkers included in the analysis were plasma cortisol, salivary cortisol, hair cortisol, infrared thermography (IRT), mechanical nociceptive threshold (MNT), substance P, kinematic gait analysis, and a visual analog scale for pain. A total of 7,992 biomarker outcomes collected from 7 pain studies involving pain associated with castration, dehorning, lameness, and abdominal surgery were included in the analysis. Each study consisted of 3 treatments: uncontrolled pain (tissue damage), no pain (handled controls), and analgesic use (tissue damage, administered a nonsteroidal anti-inflammatory drug). Results comparing analgesic effects to uncontrolled pain consistently yielded AUC values >0.7 (95% confidence interval: 0.40 to 0.99) for plasma cortisol (time points: 1.5, 2, 3, 4, 6, and 8 h), hair cortisol (time point: 62 d), and IRT (time point: 72 h). Results comparing analgesic effects to uncontrolled pain consistently yielded AUC values <0.7 (95% confidence interval: 0.28 to 0.90) for salivary cortisol (6, 13, 20, 34, 48, and 62 d); MNT (6, 25, and 49 h); substance P (1, 2, 3, 4, 6, 8, 12, 18, 24, 48, 72, 96, 120, 144, 312, 480, 816, 1,152, and 1,488 h); kinematic gait analysis including area (8, 16, 48, 72, 96, and 120 h), force (8, 16, 24, 48, 72, 96, and 120 h), and pressure (8, 16, 24, 48, 72, 96, and 120 h); and a visual analog scale for pain (1, 2, 3, 4, 5, and 6 d). These results indicate that ROC analysis can be used to characterize the predictive value of pain biomarkers and provide new knowledge on the diagnostic accuracy of pain biomarkers within this data set. This analysis, using data from 7 studies, was a preliminary approach to identify biomarkers and collection time points that could inform additional analytical approaches or meta-analyses with larger sample sizes, which are needed to further validate these hypotheses and conclusions.

Effect of a single dose of meloxicam prior to band or knife castration in 1-wk-old beef calves: I. Acute pain.

In Western Canada, approximately half of the calves produced are castrated before 1 wk of age. Therefore, it is important to identify effective analgesic drugs to mitigate pain associated with castration and consequently improve animal welfare. The aim of this study was to assess the efficacy of a single s.c. dose of meloxicam at mitigating pain associated with knife and band castration in 1-wk-old calves. Seventy-two Angus crossbred bull calves (47.3 ± 6.70 kg of body weight (BW), 1 wk old) were used in a 3 × 2 factorial design where main factors included castration method-sham (CT), band (BA) or knife (KN) castration- and medication-lactate ringer (NM) or 0.5 mg/kg BW of meloxicam (M). Measurements included different physiological and behavioral parameters. Samples were collected on day -1, immediately before castration (T0); and 60, 90, and 120 min and 1, 2, 3, and 7 d after castration except for visual analog scale (VAS) which was collected at the time of castration. The salivary cortisol concentrations were greater (P = 0.04) in KN and BA calves than CT calves 60 min after castration, while 90 min after castration BA had greater concentrations than CT calves. Substance P concentrations were greater (P = 0.04) in NM calves than M calves on d 3 and 7 after castration. The serum amyloid-A (SAA) concentrations were greater (P = 0.05) in KN calves than BA and CT calves on days 0, 2, and 3, while BA calves had greater SAA concentrations on day 7 than KN and CT calves. The visual analog scores were greater (P < 0.01) in KN calves than BA, and in BA compared to CT calves. The KN calves tail flicked more (P < 0.01) than BA and CT calves, and NM calves tail flicked more (P = 0.03) than M calves. No castration or medication effect (P > 0.10) was observed for stride length, walking, standing, lying ventral, eating, foot stamping, head turning, lying and standing percentage, performance, platelets, or body temperature. Overall, knife castrated calves exhibited a greater acute pain response than band castrated calves. Meloxicam was able to reduce substance P concentrations, white blood cell counts and number of tail flicks after castration, suggesting that the drug was able to mitigate acute pain to some extent. However, meloxicam did not have an effect on the other physiological and behavioral parameters assessed.

Effect of timing of subcutaneous meloxicam administration on indicators of pain after knife castration of weaned calves.

The newly revised Canadian Codes of Practice for the management of beef cattle requires that as of 2018, calves older than 6 mo of age be castrated using pain control. Castration is a husbandry procedure commonly done without pain control, and there is a lack of agreement on an effective pain mitigation strategy specific to castration. The aim of this study was to identify the optimal time of administration of meloxicam prior to castration. Thirty-four Angus and Angus crossbred bull calves (282 ± 28.0 kg BW) were randomly assigned to 1 of 3 treatments receiving a single s.c. injection of meloxicam (0.5 mg/kg BW): 6 h (6H; = 11), 3 h (3H; = 12), or immediately (0H; = 11) before knife castration. Measurements included visual analog scale (VAS), head movement (HM), accelerometer movement (AM) and strain gauge exertion force (EF) on the squeeze chute, stride length (SL), lying and standing behavior, salivary cortisol (SC), haptoglobin, serum amyloid A (SAA), substance P (SP), and scrotal temperature (ST). Samples were collected on d -7, -5, -2, -1, and immediately before castration (T0) and 30, 60, 120, and 240 min and 1, 2, 5, 7, 14, 21, and 28 d after castration, except for VAS, AM, EF, and HM, which were obtained at the time of castration. A time × treatment effect ( = 0.01) was observed for SP, where 0H had lower concentrations than 3H and 6H calves 1 d after castration, whereas 3H calves tended to have greater levels than 6H calves 5 d after castration. Mean ST was greater ( < 0.01) in 6H calves compared to 0H and 3H calves 120 min after castration, whereas 6H and 3H calves had greater ST compared to 0H calves 240 min after castration. On d 1 after castration, 6H calves had greater ST than 0H and 3H calves, whereas 0H calves had greater ST compared to 3H and 6H calves on d 28 after castration. The SL tended ( = 0.09) to be shorter in 3H and 6H calves than 0H calves 30, 60, 120, and 240 min after castration. Number of peaks from the AM between 2 and 3 SD above or below the mean were greater ( = 0.03) in 3H and 6H calves than in 0H calves. No treatment differences ( > 0.10) were observed for the number of peaks and area for AM and EF, VAS, HM, SC, or haptoglobin. On the basis of these results, the optimal time to administer s.c. meloxicam in 7- to 8-mo-old knife-castrated calves is immediately before castration (0H), as evidenced by fewer indicators of pain and inflammation compared to 3H and 6H calves.

Effect of band and knife castration of beef calves on welfare indicators of pain at three relevant industry ages: II. Chronic pain.

Three experiments were conducted to evaluate the effects of band and knife castration on behavioral and physiological indicators of chronic pain in beef calves at 3 different ages (36 calves/age group): 1 wk of age (Exp. 1, 4 ± 1.1 d of age, 43 ± 1.1 kg BW), 2 mo of age (Exp. 2, 63 ± 2.3 d of age, 92 ± 1.7 kg BW), and 4 mo of age (Exp. 3, 125 ± 4.6 d of age, 160 ± 3.4 kg BW). In each experiment calves were randomly assigned to either sham (CT), band (BA) or knife (KN) castration. Experiments 1, 2, and 3 ended when the testicles of banded calves had sloughed off (68, 49, and 42 d, respectively). Animal BW and rectal temperature were recorded weekly over the experimental period. Salivary cortisol, substance P, haptoglobin, scrotal area temperature using infrared thermography, visual evaluation of swelling (5-point scale), and gait stride length were collected on d -1 and immediately before castration and weekly thereafter until the end of the study. Hair samples were collected 1 d prior to and 28 d after castration and at the end of the study for cortisol concentration. Standing and lying behaviors were recorded over a 28-d period immediately after castration. No differences ( > 0.10) were observed in salivary cortisol, substance P, haptoglobin, or hair cortisol among castration methods for any of the 3 ages. No changes in behavior were observed in calves castrated at 1 wk or 2 mo of age. In 4 mo-old-calves, BA spent less time lying ( < 0.01) than CT and KN calves. Also, the average duration of lying time for BA calves was greater ( < 0.05) than for CT calves. Both, 1-wk- and 2-mo-old calves had inflammation in the scrotal area lasting 7 d after KN castration, whereas inflammation was observed for up to 14 d in 4-mo-old calves. Swelling in BA calves lasted for 21 to 28 d in the 2 younger groups of calves, whereas in 4-mo-old calves swelling was observed until d 35 postcastration. Knife- and band-castrated calves did not exhibit indicators of chronic pain or distress when the procedures were performed in calves younger than 2 mo of age. Therefore, pain mitigation should be used when castrating to improve animal welfare, especially when castrations are performed in calves older than 2 mo of age independent of the method of castration.

Effect of band and knife castration of beef calves on welfare indicators of pain at three relevant industry ages: I. Acute pain.

Three experiments evaluated the effect of band and knife castration on acute pain for the first 7 d after the procedure on 1-wk-, 2-mo-, and 4-mo-old calves. All calves were blocked by age and weight and randomly assigned to 1 of 3 treatments: sham castration (control, CT), band castration (BA), and knife castration (KN). Experiment 1 evaluated 1-wk-old Angus bull calves ( = 34; 43.0 ± 6.61 kg BW), Exp. 2 evaluated 2-mo-old Angus bull calves ( = 34; 91.5 ± 11.93 kg BW), and Exp. 3 evaluated 4-mo-old Angus bull calves ( = 35; 157.6 ± 22.52 kg BW). For all experiments, physiological and behavioral parameters were collected before (d -1 and immediately before castration [T0]) and after (60 and 120 min and on d 7) castration to assess acute pain. Physiological measures included complete blood cell count, cortisol, substance P, and scrotal temperature. Behavioral measures consisted of a visual analog scale, stride length, and time and frequency budgets for walking, standing, lying, tail flicking, foot stamping, and head turning. Performance parameters included initial and final BW and ADG. In Exp. 1, tail flicking was greater ( = 0.02) in KN calves compared to BA calves 2 to 4 h after castration, although no differences were seen between BA and KN compared to CT calves. In Exp. 2, a treatment × time interaction ( = 0.02) was observed for cortisol, where KN calves had greater cortisol concentrations 120 min after castration compared to BA and CT calves; KN calves also lay down and ate less ( < 0.01; = 0.02) and stood and walked more ( < 0.01; = 0.05) compared to BA and CT calves 2 to 4 h after castration. In Exp. 3, a treatment × time interaction ( < 0.01) was observed for cortisol concentrations in which all treatments were different from one another at 60 and 120 min, with BA calves having the greatest concentrations, KN calves being intermediate, and CT having the lowest concentrations. Overall, KN and BA castrated calves presented physiological and behavioral changes associated with acute pain; however, 2-mo-old BA calves presented the fewest behavioral changes and no physiological changes associated with acute pain compared to CT calves.

Effect of anti-gonadotropin-releasing factor vaccine and band castration on indicators of welfare in beef cattle.

Angus crossbred bulls (n = 60; 257 ± 5.4 d of age; initial BW 358.8 ± 3.78 kg) were used to study the effect of a vaccine against gonadotropin-releasing factor (GnRF) and band castration on behavioral and physiological indicators of pain. Cattle were randomly assigned to 1 of 3 treatments: bulls, band-castrated calves without pain mitigation (castrated), and immune-vaccinated animals administered an anti-GnRF vaccine (vaccinated). All animals were fitted with a radio frequency ear tag so that individual animal feed intake and feeding behavior were recorded daily over the entire trial using an electronic feed bunk monitoring system. Two doses of anti-GnRF vaccine were administrated on d -35 and 0 and band castration was performed on d 0. Animal BW was recorded weekly starting on d -36 until d 56. Visual analog scores (VAS) were measured on d -36 -35, -1, and 0, and salivary cortisol concentration was measured at -30, 0, 30, 60, 120, and 270 min on d -35 and 0 after castration. Saliva and blood were obtained on d 1, 2, 5, and 7 and weekly until d 56 for determination of cortisol and complete blood cell count. Video data were collected for pain, sexual, and aggressive behavior daily the first week and once a week until d 56. Data were analyzed with a mixed-effect model with castration, time, and their interactions as main effects. Vaccinated calves had reduced ADG and intake (P < 0.05 and P < 0.001, respectively) during the first week after vaccination. Band-castrated calves had reduced ADG and intake (P < 0.001) until the end of the study. No differences in salivary cortisol and VAS were observed among groups at d -35 after the first vaccination and before band castration. However, on d 0, castrated cattle had greater cortisol concentrations and VAS (P < 0.05 and P < 0.01, respectively) than bulls and vaccinated animals. Complete blood cell count did not differ (P > 0.05) between treatments on d 0, 1, and 2. At d 56, vaccinated calves had greater (P < 0.05) final BW than band-castrated calves and both had less final BW than bulls. There was no indication that vaccination caused any physiological or behavioral changes indicative of pain. In contrast, band castration resulted in elevated cortisol scores and VAS indicative of a pain response and behavior related to pain (P < 0.001) until d 42 of the study. The present study demonstrates that anti-GnRF vaccine is a viable animal welfare-friendly alternative to traditional band castration in beef cattle under North American feedlot practices.

Interstitial pneumonia in feedlot cattle: concurrent lesions and lack of immunohistochemical evidence for bovine respiratory syncytial virus infection.

The objectives of this study were to describe the nature and distribution of microscopic lung lesions in feedlot cattle with interstitial pneumonia and to determine whether bovine respiratory syncytial virus (BRSV) antigen was present in affected lungs. Lungs with macroscopic lesions compatible with interstitial pneumonia were collected from cattle from 5 west-central Saskatchewan feedlots that had been on feed for greater than 60 days at the time of death. Interstitial pneumonia was most consistently present in dorsal portions of caudal lung lobes and in 21/28 cases (75%) had a multifocal to coalescing distribution. All 28 lungs exhibited hyaline membrane formation and some degree of type II alveolar epithelial cell hyperplasia, consistent with an acute to subacute duration. Twenty-one of 28 cases (75%) had concurrent bronchopneumonia in at least 1 lung lobe; bronchopneumonia was grossly evident in 9/28 cases (32%). Chronic bronchitis or bronchiolitis was present in at least 1 section in 12/28 (43%) of the lungs, and 25/28 (89%) had at least 1 focus of bronchiolitis fibrosa obliterans. Bronchopneumonia and bronchiolitis fibrosa obliterans were markedly less common in 10 sets of bovine lungs obtained from an abattoir. Bovine respiratory syncytial virus antigen was demonstrated using immunohistochemistry in 2/28 cases and was associated with bronchiolar epithelial necrosis that was more severe than the bronchiolar lesions in the BRSV antigen-negative cases. Interstitial pneumonia in feedlot cattle in this study was more frequently associated with suppurative bronchopneumonia and bronchiolitis fibrosa obliterans than with BRSV infection.

Associations between oil- and gas-well sites, processing facilities, flaring, and beef cattle reproduction and calf mortality in western Canada.

From the fall of 1992 through calving 1996, detailed cow breeding outcome records were maintained actively for seven large cow-calf herds in western Canada. The numbers of mature females in the study for the breeding seasons beginning in 1992, 1993, 1994, and 1995 were 1122, 1177, 1251, and 1236, respectively. Outcomes included pregnancy status, calving interval, and the occurrence of twins, abortions, stillbirths, and neonatal mortality. Information also was collected on other risk factors known to influence beef-herd health and productivity. Detailed maps of active and inactive oil and natural-gas sites, batteries, compressor stations and processing plants were verified. Records of flaring activity at each facility were obtained from the government regulatory agency. Each flaring site then was classified as sour or sweet based on the presence or absence of hydrogen sulfide in the flared gas. A detailed inventory was prepared itemizing the type and number of facilities within 1.6 km (1 mile) of the center of each quarter section used for pasture. The total volume of gas flared within 1.6 km of the center of each pasture was determined for each month of the study. Appropriate risk periods where specified for each outcome and a cumulative exposure calculated for each breeding female (using detailed individual-animal records of cow movements between pastures and herd-management groups). Generalized estimating equations were used to evaluate the association between exposure and outcome and to adjust for potential confounders and clustering of binomial outcomes within herd. Increased risk of non-pregnancy was sometimes associated with exposure to one or more of the following facility types: sour-gas flaring battery facilities, all battery-flaring sites, active gas wells, and larger field facilities. The associations were not, however, consistent among years or even among risk periods for the same year. Facility proximity and flaring were not associated with increased abortion risk. Volume of flared sour gas from battery sites was associated with increased risk of stillbirth. Finally, sour-gas flaring was associated with increased calf-mortality risk for the 1992-1993 calf crop. Several examples of associations between exposure and increased productivity also were found (most of which involved either oil wells or all well sites).

Associations between total sulfation, hydrogen sulfide deposition, and beef-cattle breeding outcomes in western Canada.

Beef cows sometimes are pastured close to oil- and gas-production and processing facilities. We measured the health and productivity of cow-calf herds with differing exposure to sour-natural-gas processing facilities in western Canada. In seven cow-calf herds, the numbers of eligible mature females included in the study for the breeding seasons beginning in 1993, 1994, and 1995 were 1177, 1251, and 1236, respectively. Outcomes included pregnancy status, calving interval, and the occurrence of twins, abortions, stillbirths, and neonatal mortality. Information also was collected on other risk factors known to influence beef-herd health and productivity. Monthly measurements from a network of passive air-monitoring devices were used to estimate exposure. Total sulfation and H2S deposition were used as markers for the complex mixture of compounds found in emissions from sour-gas processing plants and sour flares. Most herds were managed in multiple pasture groups. Cumulative exposure assessments were made from records of individual-animal movements between pastures. Generalized estimating equations were used to evaluate the association between exposure and outcome and to adjust for potential confounders and clustering of binomial outcomes within herd. No consistent associations were found between either total sulfation or H2S deposition and productivity parameters across the cow-calf production cycles. There were, however, five examples of significant associations between increasing cumulative exposure to total sulfation and decreased productivity in the 18 models examined.

Efficacy of immunization of feedlot calves with a commercial Haemophilus somnus bacterin.

Two cohorts, consisting of 10,723 calves total, were identified in this prospective follow-up study to investigate whether immunization of auction market beef calves immediately upon arrival at the feedlot with a commercial Haemophilus somnus whole cell killed bacterin would reduce subsequent mortality. In addition to mortality rate, the use of incidence rate of fatal disease is introduced as an effect measure to examine vaccine efficacy in the feedlot. The Haemophilus somnus bacterin had no significant effect on the overall crude mortality rate; however, the bacterin appeared to significantly (p less than 0.05) reduce the incidence rate of fatal disease and the mortality rate during the first two months in the feedlot, when risk of fatal disease onset was highest. Once mortalities likely not associated with hemophilosis (for example, a fractured femoral neck) were removed from the analysis, steer mortality rate, but not heifer mortality rate, was reduced significantly (p less than 0.05) in the vaccinated group. The attributable percent overall for steers was 17.4%; this suggests that 17.4% of fatal respiratory disease in the unvaccinated steers could have been prevented by vaccination with the H. somnus bacterin. Heifer calves demonstrated a significantly (p less than 0.01) higher incidence rate of fatal disease during the first week than did steer calves, indicating that a different pattern of fatal disease existed for the two sexes. Use of a second vaccination two weeks after arrival did little to decrease mortality risk.

Factors associated with average daily gain, fever and lameness in beef bulls at the Saskatchewan Central Feed Test Station.

Data obtained from the Saskatchewan Central Feed Test Station in Saskatoon, Saskatchewan, Canada were examined for evidence of factors related to average daily gain and the diseases occurring in 326 beef bulls during the 1983-84 test. Average daily gain was found to be significantly associated with breed, pen assignment and initial test weight but was not associated with disease or age upon arrival at the test station. Lameness was associated with breed and initial weight, while fever (suspected respiratory disease) was associated with age. The predicted odds of lameness was approximately seven times greater in the animal with the heaviest as compared to the lightest initial test weight and the predicted odds of fever was approximately five times greater in the youngest as compared to the oldest animal.

The predictive value of pelvimetry in beef cattle.

To elucidate reasons for failure of pelvimetry to predict dystocia, we collected data from 1146 heifers and 210 cows in five beef cow herds in Saskatchewan. We assessed the reliability of pelvic area measurements, the generalizability of findings, various modifications of the technique, and the statistical association between pelvic area measurements and dystocia. The repeatability (kappa) of pelvic area measurements between and within veterinarians for the Rice and Krautmann pelvimeters were low to moderate, indicating pelvic area measurements were imprecise. The positive predictive values and sensitivities of pelvic area measurements were consistently poor across herds, years of study, breeds of heifers, times of measurement, various pelvic area cut-off points, and sires. Various modifications of the technique, including pelvic area/calf birth weight ratios, pelvic area/heifer weight ratios, and Ko's calving prediction equation were also poor on-farm tests for predicting dystocia. Although the mean pelvic area in heifers with dystocia was smaller than those without dystocia, there was a large overlap in the distribution of their measurements. Far too many heifers with a small pelvic area had no dystocia (false positives) and far too many heifers with a large pelvic area had dystocia (false negatives) for pelvimetry to be useful. We conclude there is little evidence to justify the continued use of pelvimetry as an on-farm test to reduce dystocia in beef cattle.

Effect of time of year, weather, and the pattern of auction market sales on fatal fibrinous pneumonia (shipping fever) in calves in a large feedlot in Alberta (1985-1988).

A total of 58,885 spring-born calves entering a large commercial feedlot in southwestern Alberta were studied to examine the associations between shipping fever mortality and the pattern of calf sales at the auction markets, time of year, and weather. The observational study followed calves purchased from 42 auction markets in the 4 western provinces between September 1 and December 31 in each of the years from 1985 to 1988. Calf sales at the auction markets consistently peaked during the last week of October and the first week of November. Calves entering the feedlot in November had a risk of fatal shipping fever 2 to 8 times greater than calves entering in September or December. The pattern was the same for all 4 years, with maximum risk occurring 2 to 4 weeks after the peak time for calf sales at the markets. A number of factors could have contributed to this pattern, including changes in transport truck availability, changes in the density of calves at the markets, changes in population dynamics at the feedlot that affected feedlot crew efficiency, and weather. The finding that the risk of fatal shipping fever appears to increase significantly as the feedlot fills with calves in the fall deserves the attention of feedlot owners, so they can design their treatment strategies appropriately, and of researchers, who may gain useful knowledge about the natural history of the disease by investigating why this change in risk occurs.

The prevalence of bovine viral diarrhea virus infection in a population of feedlot calves in western Canada.

The prevalence of bovine viral diarrhea virus (BVDV) infection was examined in a population of 5129 recently weaned steer calves entering a large feedlot in central Saskatchewan from September to December 1991. Serum samples were collected within 24 h of arrival at the feedlot from every fifth calf processed and again 96 d postarrival. A microtiter virus isolation test was used to determine the prevalence of calves viremic with BVDV on entry to the feedlot. An enzyme-linked immunosorbent assay (ELISA) which detects antibody against glycoprotein 53 of the BVDV was used on paired sera to determine the seroconversion risk during the first 96 d in the feedlot. A virus neutralization (VN) test for BVDV was conducted on a sub-sample of paired sera to measure agreement in determination of seroconversion risk with the ELISA. A polymerase chain reaction (PCR) test which detects BVDV was used to determine if cattle were acutely viremic when treated for disease. The estimated prevalence of persistently infected calves in this population was < 0.1%. The seroconversion risk for BVDV was 27% (236/864) according to the ELISA and it varied from 0 to 63% among the 20 pens sampled. According to the VN test, the seroconversion risk for BVDV was 40% (132/327) and it varied from 0 to 100% among the 11 pens tested. The agreement between the ELISA and VN tests in seroconversion risk to BVDV was very poor (kappa = 0.15 +/- 0.039 SE). The prevalence of acute viremia in calves treated at the feedlot hospital was low at 4% (6/149).(ABSTRACT TRUNCATED AT 250 WORDS)

Depletion of intramuscularly and subcutaneously injected procaine penicillin G from tissues and plasma of yearling beef steers.

Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine penicillin G/kg body weight were administered to yearling beef steers by intramuscular injection daily for five consecutive days were investigated. These dosages are in excess of product label recommendations, but are in the range of procaine penicillin G dosages that have been administered for the treatment of some feedlot bacterial diseases. The approved dose in Canada is 7,500 IU/kg body weight intramuscularly, once daily, with a withdrawal period of five days. Based on the tissue residue data from this study, the appropriate withdrawal period is ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg body weight dose when administered intramuscularly to yearling beef steers. In a related study, 18 yearling beef steers received 66,000 IU of procaine penicillin G/kg body weight administered by subcutaneous injection, an extra-label treatment in terms of both dose and route of administration, typical of current practice in some circumstances. Deposits of the drug were visible at subcutaneous injection sites up to ten days after injection, with more inflammation and hemorrhage observed than for intramuscular injections of the same dose. These results suggest that procaine penicillin G should not be administered subcutaneously at high doses; and therefore a withdrawal period was not established for subcutaneous injection.

Disposition of penicillin G after administration of benzathine penicillin G, or a combination of benzathine penicillin G and procaine penicillin G in cattle.

Plasma concentration of penicillin G was evaluated in beef steers after administration of either a combination of benzathine penicillin G and procaine penicillin G in a 1:1 mixture at a dosage of 9,000 U/kg of body weight, IM (n = 5), 24,000 U/kg, IM (n = 5), or 8,800 U/kg, SC (n = 5), or benzathine penicillin G alone at a dosage of 12,000 U/kg, IM (n = 7). Plasma concentration of penicillin G was measured by use of a high-performance liquid chromatography assay that had a limit of determination of 0.005 microgram/ml. At a dosage for this combination of 9,000 U/kg IM, and 8,800 U/kg, SC, which are approved label recommendations in Canada, and the United States, respectively, mean (+/- SEM) peak plasma concentration was 0.58 (+/- 0.15) and 0.44 (+/- 0.02) microgram/ml, respectively. Although plasma penicillin concentration was quantifiable for 7 days in the steers that received 9,000 U/kg, IM, and for 4 days in the steers that received 8,800 U/kg, SC, the concentration was < 0.1 microgram/ml in both groups after the first 12 hours. After administration of the combination at dosage of 24,000 U/kg, IM, there was an initial peak plasma concentration at approximately 2 hours; thereafter, plasma concentration decreased slowly, with half-life of 58 hours. Although plasma penicillin G concentration was quantifiable for 12 days at this dosage, concentration was < 0.1 microgram/ml after the first 48 hours. After the initial 48 hours, plasma concentration of penicillin was of similar magnitude and decreased at similar rate for the combination at dosage of 24,000 U/kg and for 12,000 U/kg of benzathine penicillin G alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of the association between Neospora caninum infection and reproductive performance in beef herds.

OBJECTIVE: To determine seroprevalence of Neospora caninum infection in beef herds and the association between serologic status and rate of abortion, stillbirth, calf mortality, and reproductive failure. DESIGN: Longitudinal study. ANIMALS: 419 cows from 8 beef herds in central Alberta. PROCEDURE: 1,391 serum samples from a serum bank were analyzed, using ELISA, and results were compared, using logistic regression, with productivity data on individual cows obtained from a database established during a 4-year period. RESULTS: 30% of cows were seropositive at some point during the 4-year period. Risks of abortion (odds ratio [OR], 5.7) and stillbirth (OR, 2.8) in seropositive cows were significantly greater than in seronegative cows. Risks of being culled for any reason (OR, 1.9) or for reproductive failure (OR, 2.5) in seropositive cows were also significantly greater than in seronegative cows. Changes in titer with time in individual cows and a lack of association between serologic status of dam versus daughter suggest that postnatal transmission was possible in these herds. However, horizontal transmission did not appear to play a substantial role in abortions that occurred in these herds. CLINICAL IMPLICATIONS: Neosporosis should be investigated as a potential source of economic loss to the beef industry.

Evaluation of the impact of a natural gas leak from a pipeline on productivity of beef cattle.

OBJECTIVE: To determine the association between a leak of sour natural gas (more than 30% hydrogen sulfide) from a pipeline in a river valley and the health of beef cattle in the intensively ranched surrounding area. DESIGN: Prospective cohort study. SAMPLE POPULATION: 13 herds of cattle within 4 km (2.5 miles) of the leak and 10 herds outside the 4-km zone. PROCEDURE: Distance of herds from the leak site was determined, using geographic information system technology. Information about speed and direction of winds was obtained from a local meteorologic station and an ambient air-quality monitoring trailer. Health and productivity data for surrounding beef herds, as well as exposure information, were collected and analyzed. RESULTS: An association was not found between total herd calf mortality and herd distance from the leak, wind-aided exposure, location in the river valley, signs of irritation consistent with exposure to the gas, or reports of odors of gas at the time of the leak. Management changes reported in response to the gas leak were identified as risk factors for total herd calf mortality. Other herd-level risk factors associated with increased calf mortality ratio included a median calving date in February and percentage of twin births for a herd. CLINICAL IMPLICATIONS: In this example, we did not detect an association between productivity of cattle and exposure to sour natural gas. Several methods can be used for ranking potential exposure after discovery of a leak.

Outbreak of abortion associated with Neospora caninum infection in a beef herd.

Abortion outbreaks caused by infection with Neospora caninum in beef cattle have not been well documented. Neospora caninum infection was confirmed in 4 fetuses that were aborted by cattle in a 350-head beef herd; an additional 58 cattle aborted during the next 2.5 months. Overall, 44.4% (157/354) of the cattle in the herd did not become pregnant or experienced fetal loss during this period. Initially, 81.3% (282/347) of the herd was seropositive for antibodies to N caninum, and seropositive cows were 6.2 times as likely to not be pregnant as were seronegative cows. Other potential causes of abortion were not identified in this herd. Following the outbreak, few cattle in the herd or in a second exposed herd seroconverted, but high antibody titers persisted in most seropositive cattle through the end of the calving season. Evidence of cow-to-fetus transmission of the organism was detected in > 82% of seropositive cows.

Prophylactic medication of feedlot calves with tilmicosin.

The parenteral administration to calves of the antibiotic tilmicosin either on arrival at a feedlot or 72 hours later was evaluated in a group of 308 steer calves. The calves were allotted to 24 pens so that there were eight replicates of the two medicated groups and eight replicates of the control group. The need for veterinary treatment was reduced significantly (P less than 0.05) during the first month of the feeding period in the two medicated groups. The medicated groups had an improved average daily weight gain (P less than 0.01) over the trial period compared with the non-medicated animals. This improved average daily gain by the medicated groups was not reduced when animals with respiratory disease were excluded from the calculations. The medicated groups also had an improved feed conversion efficiency (P less than 0.01) over the first 60 days of the feeding period compared with the non-medicated animals.