The effect of bethanechol, neostigmine, metoclopramide, and propranolol on myoelectric activity of the ileum, cecum, and proximal loop of the ascending colon was determined in 6 healthy Jersey cows implanted with 8 pairs of bipolar electrodes. Assigned at random, each cow received each of 5 treatments in 3-day intervals. The treatments included bethanechol (0.07 mg/kg of body weight, SC), neostigmine (0.02 mg/kg, SC), metoclopramide (0.15 mg/kg, IM), DL-propranolol (0.2 mg/kg, IM), and 0.9% sodium chloride (NaCl) solution (20 ml, SC). All drugs were administered during early phase I of the migrating myoelectric complex in the ileum. Myoelectric activity was recorded for 4 hours after treatment, and data were analyzed for each hour separately. Bethanechol and neostigmine significantly (P < 0.05) increased the number of cecocolic spikes per minute per electrode, duration of cecocolic spike activity (%), and number of cecocolic propagated spike sequences per 10 minutes, relative to NaCI, during 1 or more hours of the recording period. The effect of bethanechol was more pronounced on duration of spike activity and number of propagated spike sequences, whereas neostigmine mainly increased the number of (uncoordinated) spikes. Metoclopramide and propranolol had no significant effect on cecocolic myoelectric activity, relative to NaCl. It was concluded that bethanechol and, less likely, neostigmine at the dosage used in this study may be suitable for medical treatment of cecal dilatation in cattle in which hypomotility of the cecum and proximal loop of the ascending colon has to be reversed. The potential advantage of bethanechol vs neostigmine for medical treatment of cecal dilatation is worth further evaluation.

Association between individual cumulative milk yield and various reproductive disorders in 56,772 Finnish Ayrshire cows belonging to 5,912 herds in 80 communities was studied. All cows delivered calves between September 1985 and September 1986. Five logistic regression models were fitted, 1 for each outcome disorder of interest: early metritis, late metritis, silent heat, ovarian cyst, and other infertility. Cumulative individual 37-day milk yield was used in the early metritis model, and cumulative individual 60-day milk yield was used in the other models, on the basis of median days in milk when these disorders developed. Cumulative 305-day herd milk yield, parity, calving season, presence or absence of other disorders, and community were also included in the models. Point estimates from the models represented odds ratios for the likelihood of having the outcome disorder.Lactational incidence risks for the 5 reproductive disorders studied were: early metritis (2.4%), late metritis (1.1%), silent heat (5.4%), ovarian cyst (6.6%), and other infertility (2.1%). The risk of early metritis decreased with increasing 37-day milk yield. The risk of silent heat, ovarian cyst, and other infertility increased with increasing 60-day milk yield; 60-day milk yield had no effect on late metritis. The 305-day herd milk yield increased the risk of early metritis, ovarian cyst, and other infertility; it had no effect on late metritis or silent heat. Parity had an effect on all disorders, except late metritis. Cows that delivered calves during the colder, darker seasons of the year had a higher risk of reproductive disorders than did those that delivered calves at other times of the year. A number of other disorders, reproductive and otherwise, were significant predictors of development of the outcome disorders.

We characterized the clinicopathologic manifestations of experimentally induced endotoxin-induced mastitis. Responses to hypertonic fluid therapy also were assessed. Eight cows received 1 mg of endotoxin by in infusion in the left forequarter. Four hours after endotoxin administration, cows received 0.9% NaCl, 5 ml/kg of body weight (n = 4) or 7.5% NaCl, 5 ml/kg (n = 4) IV. Endotoxin-infused cows had expanded plasma volume, hyponatremia, transient hyperchloremia and hypophosphatemia, increased serum glucose concentration, and decreased serum activities of liver- and muscle-specific enzymes. Calculated plasma volume increased at 6 hours in cows receiving hypertonic NaCl, and at 12, 24, and 48 hours after endotoxin infusion in both groups. Concurrent observations of decreased serum protein concentration, erythrocyte count, and hematocrit supported observations of increased plasma volume. Relative plasma volume was greater in cows receiving hypertonic NaCl (124.3%) than in cows receiving isotonic NaCl (106.6%) at 6 hours after endotoxin infusion. Cattle receiving hypertonic NaCl had increased voluntary water intake after IV fluid administration. Increased water consumption was not accompanied by increased body weight, indicating probable occurrence of offsetting body water loss. Serum sodium concentration in cows receiving hypertonic NaCl was increased 2 hours after fluid administration, but the magnitude of the change was minimal (< 4 mmol/L) and transient, indicating rapid equilibration with either interstitial or intracellular spaces. Serum sodium concentration was decreased in cows receiving isotonic NaCl at 12, 24, and 48 hours after endotoxin administration, compared with concentration prior to endotoxin administration, indicating selective loss of sodium.

The role of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor a during endotoxin-induced mastitis in cows was characterized. Six cows had 10 microgram of Escherichia coli lipopolysaccharide infused into 1 mammary gland. Three other cows served as nontreated controls. Within 1.5 to 2.5 hours after infusion, endotoxin caused obvious edema of the mammary gland and increased serum albumin concentration in milk of infused glands 6 times. Milk somatic cell count began to increase 3 to 5 hours after infusion in all treated glands. At 7 hours after infusion, somatic cell counts were increased > 10 times, compared with counts in milk from control cows. Pyrexia of > 1 C developed in only 1 cow, but all treated cows had serum cortisol concentrations > 50 ng/ml in response to endotoxin treatment. High concentrations of IL-1 (10 to 600 U/ml) and IL-6 (2 to 22 U/ml) were detected in milk of infused glands beginning 2.5 to 4 hours after infusion. Endotoxin did not induce detectable amounts of tumor necrosis factor activity in milk or serum. Swelling and mammary gland permeability changes preceded any detectable increase in IL-1 and IL-6 activity, indicating that these clinical signs of inflammation were not mediated by these cytokines. Systemic responses and the leukocytic influx into endotoxin-infused glands developed after or concurrently with initial increases in IL-1 and IL-6 activities in milk. These results suggested that IL-1 and IL-6 may have a role in mammary gland defenses and in the pathophysiologic changes during endotoxin-induced mastitis.

Body condition scoring (using a 5-point with quarter-point divisions) was performed on 66 Holstein dairy cows that began their second or later lactation in August, September, or October 1988. Cows' body condition was scored beginning on postpartum day 4 (+/- 1) and subsequently at postpartum days (+/- 1) 18, 32, 46, 60, 73 and 87. Blood samples were obtained on the same dates. Reproductive health examinations were conducted by 1 of 2 veterinarians beginning at postpartum day 21. Reproductive performance was evaluated in relation to body condition score and serum urea nitrogen and cholesterol concentrations. Number of days to first recorded signs of estrus and first breeding were not related to body condition score at calving, amount of condition loss, cumulative 80-day milk yield, or 305-day fat corrected milk yield. Cows that calved with body condition score greater than or equal to 3.50 required more days to conceive. Cows losing > 0.75 points of condition had longer days of conception. Body condition score at calving and amount of condition lost were not related to services per conception or diagnosis of follicular cyst. Cumulative 80-day milk yield was not related to days to conception or services per conception. Cows that produced greater than or equal to the mean 305-day milk yield required more services and had longer days to conception than cows that produced < the mean 305-day milk yield. Cows with diagnosis of ovarian follicular cysts had greater cumulative 80- and 305-day milk yields than did cows that were not diagnosed with follicular cysts. Cows conceiving with less than or equal to 2 services did not differ in average daily milk production, body condition score, or serum urea nitrogen concentration from cows conceiving with > 2 services, but cows that conceived with less than or equal to 2 services had higher serum cholesterol values than did cows requiring more services.

Immunoglobulin reactions to Salmonella dublin in serum and milk from 4 groups of lactating cows were measured by an indirect ELISA. The groups consisted of (1) cows that were natural carriers of S dublin in the mammary gland, (2) experimentally infected cows that did not become carriers, (3) cows inoculated with a commercial S dublin bacterin, and (4) cows used as S dublin-negative controls. Milk and serum samples were obtained at monthly intervals. Models for predicting carrier status were developed by use of stepwise logistic regression. Independent variables consisted of serum and milk IgG and IgM titers to S dublin lipopolysaccharide and a ratio of IgG to IgM. The utility of a single sample vs multiple samples obtained at 1-month or 2-month intervals was tested by comparison of goodness-of-fit X2 P values for 8 models predicting carrier status. Immunoglobulin reactions specific to S dublin were a significant predictor of carrier status (P < 0.001). Serum IgG titers specific for S dublin were the most important variable for predicting carrier status. Two serum IgG titers to S dublin obtained 2 months apart was a better predictor of carrier status than measurement of the IgG:IgM ratio from a single serum sample. Immunoglobulin recognizing S dublin epitopes also were detected in milk samples. In milk, performing 2 ELISA 60 days apart to determine IgG and IgM reactions to S dublin appeared to be useful for the prediction of carrier status, but was not as accurate as models for serum immunoglobulin reactions.

Because caffeine is metabolized by the hepatic P-450 cytochrome oxidase system, clearance of caffeine is an excellent quantitative test of hepatic function in human beings. It is currently used in much the same way that creatinine clearance is used to assess renal function. Caffeine clearance was measured in lactating dairy cows initially to determine the suitability of caffeine clearance as an indicator of hepatic function in cattle. Pharmacokinetic variables of caffeine were studied in 6 adult lactating dairy cows after IV administration of a single dose of caffeine sodium benzoate (2 mg of caffeine/kg of body weight). Caffeine concentration was analyzed by use of an automated enzyme immunoassay. The lower limit of detection of the assay for caffeine in serum was 0.079 micrograms/ml. Serum caffeine concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean elimination half-life was 3.8 (range, 2.6 to 6.9) hours, and total clearance was 0.118 (range, 0.090 to 0.197) L/kg/h. Milk caffeine concentration was similar to serum concentration 1.5 to 24 hours after caffeine administration. Adverse effects were not observed in cows given caffeine.

Eight Holstein cows, 4 inoculated intracisternally in 1 quarter of the mammary gland with Escherichia coli and 4 noninfected controls, were administered ceftiofur sodium (3 mg/kg of body weight, IV, q 12 hours) for 24 hours, beginning at 14 hours after inoculation of infected cows. All challenge-exposed cows became infected, with mean +/-SEM peak log10 bacterial concentration in milk of 5.03 +/-0.69 colony-forming units/ml. The infection resulted in systemic signs (mean peak rectal temperature, 41.5 +/- 0.3 C; anorexia; signs of depression) and local inflammation (mean peak albumin concentration in milk, 7.89 +/- 1.71 mg/ml). Ceftiofur was detectable in milk from all challenge-exposed cows, compared with only 1 of 4 noninfected cows, and the mean period after inoculation that ceftiofur was detectable in milk was longer (P < 0.05) in infected (147.7 +/- 27.5 hours) than noninfected cows (1.3 +/- 1.3 hours). However, maximal ceftiofur concentration attained in milk for all cows was 0.28 micrograms/ml, and was 0.20 micrograms/ml or less for all but 2 milk samples collected for 10 days after challenge exposure. Mean serum concentration of ceftiofur peaked at 1.0 +/- 0.3 micrograms/ml and 0.7 +/- 0.1 micrograms/ml for infected and noninfected COWS, respectively. After each ceftiofur dose, mean peak and trough concentrations of ceftiofur in serum did not differ between groups; however, concentration of ceftiofur in serum was higher at 7 hours after each dose in noninfected cows, suggesting more rapid clearance of the drug in infected cows. Ceftiofur was not detected in serum (< 0.05 micrograms/ml) of any cow at or after 120 hours following inoculation of infected cows Storage of serum samples at -20 C for 3 weeks resulted in a 98.8% decrease in ceftiofur activity, compared with that in fresh serum samples. Eighty-seven percent of this loss occurred 30 minutes after mixing serum and ceftiofur; thus, about 13% of the original activity was lost in storage.

Samples of serum and urine were obtained simultaneously from 56 healthy lactating cows to determine ranges of fractional excretion (FE) of calcium (Ca), phosphate (PO4), magnesium (Mg), sodium (Na), potassium (K), and chloride (Cl). Samples were obtained at 3 stages of lactation: period 1 = 1 to 7 days, 2 = 83 to 112 days, and 3 = 175 to 197 days. The FE of electrolytes were significantly different among periods 1, 2, and 3 for Ca (P < 0.001), PO4 (P < 0.025) and Mg (P < 0.025), but were not significantly different for Na, K, and Cl. Least squares mean FE of Ca was lowest in period 1 and not significantly different for periods 2 and 3, whereas mean FE values for PO4 and Mg were highest in period 2 and not significantly different for periods 1 and 3. The mean FE values of Na, K, and Cl did not change with stage of lactation. Age and category of milk production (high, medium, and low) did not influence the FE values of the electrolytes.