Surveillance study of novobiocin and phenylbutazone residues in raw bovine milk using liquid chromatography-tandem mass spectrometry.

A simple method permitting the simultaneous determination of trace residues of novobiocin and phenylbutazone in raw milk samples using liquid chromatography-tandem mass spectrometry was developed. Raw milk samples were mixed with acetonitrile to facilitate the concurrent precipitation of milk proteins and extraction of both veterinary drugs. Without additional clean-up or concentration of the resulting extract, the analytes could be quantified at concentrations as low as 0.0025 and 0.001 microg ml(-1) for phenylbutazone and novobiocin, respectively. The analysis of a series of fortified raw milk samples at analyte concentrations ranging from 0.005 to 0.1 microg ml(-1) and from 0.01 to 0.2 microg ml(-1) for phenylbutazone and novobiocin, respectively, yielded average recoveries ranging from 89.2% to 104.3% with standard deviations below 7%. The analytical method was applied to the analysis of raw milk samples collected from transport trucks upon delivery at dairy-processing plants throughout Alberta, Canada. Novobiocin was detected in 13 of 1072 samples tested at concentrations ranging from 0.001 to 0.007 microg ml(-1). Phenylbutazone was not detected in any of the samples tested.

Brainstem auditory evoked potentials in liver transplant candidates.

BAEPs were recorded on 18 patients before, and/or after liver transplantation. Clinical assessment included 5 standardized scales. Data were divided by stringent criteria into 2 groups: clinical hepatic encephalopathy present (HE) or absent (nonHE). Dependent variables were BAEP configuration and I-V, I-III and III-V IPLs. The following comparisons were made: all patients vs. controls; HE vs. controls; nonHE vs. controls; HE vs. nonHE. BAEP configuration changes were not significantly associated with HE. I-V and III-V IPLs were prolonged for all patients, nonHE patients, and HE patients vs. controls; I-III IPL differences were not significant. There were no correlations between BAEP variables and EEG grade or grades on any single clinical scale. The results suggest that BAEP IPLs (especially the I-V IPL) are a sensitive, although not specific, measure of HE and may be sensitive enough to detect incipient HE.

Aldrin intoxication and clearance of associated dieldrin residues in a group of feedlot cattle.

A sudden onset of bizarre neurologic dysfunction was found in 8 of 90 mixed-breed feeder calves. Seven other calves were dead, and 3 more died during the next week. A diagnosis of organochlorine toxicosis was made when rumen and abomasal contents from 1 of the calves revealed 22.4 and 20.6 micrograms of aldrin/g of ingesta, respectively. Complete feeds retrieved from self-feeders contained 54 and 528 micrograms of aldrin/g of feed. The initial concentration range in fat from 40 live calves was 6.01 to 42.44 micrograms of dieldrin/g of fat. Additional fat samples were analyzed to verify residue compliance until the entire herd was clear of residue 18 months after removal of the contaminated ration. The range of apparent half-lives for dieldrin in body fat of heifers and steers was 69 to 231 and 53 to 116 days, respectively. These findings demonstrate the considerable variability in apparent half-life of dieldrin in field cases. In cases of dieldrin-contaminated livestock, veterinarians and regulatory personnel must accurately determine the necessary slaughter withholding times so that informed economic decisions are made in the best interest of the producer while enhancing the probability of a safe food supply. Excretion rates of dieldrin from field-contaminated cattle may not be consistent with results obtained under experimental conditions.

Theophylline-mexiletine interaction: a case report.

Theophylline and mexiletine can be prescribed in patients with chronic obstructive pulmonary disease with coexistent arrhythmias. The drugs have common metabolic pathways that may result in an interaction. A patient who was taking theophylline became toxic after the initiation of mexiletine. Discontinuation of mexiletine led to an improvement in theophylline clearance.

Systemic glycoproteinosis resembling Lafora's disease in a cow.

A 6-year-old, Hereford/Angus crossbred cow which died acutely was submitted for necropsy and diagnostic evaluation. A toxicity was suspected by the owner who had noticed incoordination of one week's duration. The animal was last observed 24 hours prior to death. Toxicology screens for alkaloids, heavy metals, pesticides and nitrates were negative. The significant histologic abnormalities were confined to the thalamic nuclei, periventricular neurons and the liver. Neurons and hepatocytes contained 1 to 2 intracytoplasmic inclusions which stained faintly eosinophilic to slightly basophilic with H&E. The inclusions frequently had dense central cores and a fibrillar to homogeneous periphery. Based on a battery of histochemical stains for carbohydrates, and other mucosubstances and the morphology and location of the inclusions, a diagnosis of systemic glycoproteinosis consistent with Lafora's disease was made. This case represents the first report of lesions consistent with Lafora's disease in the bovine species.

Organochlorine insecticide problems in livestock.

1. Antidotal therapy for acute OC intoxications is symptomatic and supportive. Use sedatives to control convulsions and AC to adsorb any pesticide remaining in the gut, and wash topical exposures. 2. Published kinetics should be applied to field situations with caution. In general, residues decline relatively quickly immediately following the last exposure; thereafter, the rate slows considerably. The elimination-rate constant and, hence, the half-life of any given OC is dependent on many variables that usually are not known under field conditions. This fact may result in serious errors if literature values are relied on too heavily in predicting the outcome of "natural" contamination. As a rule of thumb, elimination data derived from animals experimentally fed to plateau concentrations may be regarded as fairly conservative for such purposes, if the contaminated animals are maintained in a normal fashion. Probably the least risky method of predicting return to marketability is using frequent samples, taken at regular intervals (for example, 1 to 2 weeks) during the first month after last exposure, to adjust literature values. 3. Residues from larger dosages and shorter exposures tend to be smaller in proportion to dose and are eliminated more quickly than those resulting from longer exposures and smaller doses. 4. Activated charcoal is of universal benefit only if given immediately after exposure. 5. Pharmaceutical modifiers of xenobiotic metabolism such as phenobarbital are of very limited value. The particular type and amount of residual OC and the potential economic benefit of therapy should be considered thoroughly before undertaking such therapy. In most cases, the expense won't be justified. 6. Mineral oil increases the fecal excretion of some OC. Fecal excretion, however, is so small in relation to total body burdens that even a several-fold increase may not be useful economically except when residue concentrations are low to start with. 7. Nutritional strategies have the advantage of being very cheap. Practitioners should remember, however, that tissue concentrations actually may increase as body fat decreases. The costs of maintaining animals for an extra 6 to 10 months should be considered before undertaking such an effort.(ABSTRACT TRUNCATED AT 400 WORDS)

In vitro reassembly of infectious polyoma virions.

Initial experiments in our laboratory have successfully reassembled infectious polyoma virions from dissociated virion products. Virions treated with ethyleneglycol-bis-N,N'-tetraacetic acid and the reducing agent beta-mercaptoethanol at pH 7.5 were dissociated to a 48S DNA-protein complex and capsomere subunits. The virion dissociation products were not infectious by plaque assay and lacked hemagglutination activity. These virion dissociation products were reassembled to intact virions by overnight dialysis against a reassembly buffer containing CaCl2, dimethyl sulfoxide, and Triton X-100 in phosphate-buffered saline at pH 7.4. The biophysical characteristics of the reassembled virions were identical to those of untreated virions in that the reassembled virions had a sedimentation value of 240S in sucrose gradients and a buoyant density of 1.315 g/cm3 in CsCl isopycnic gradients. The reassembled virions were intact as determined by electron microscopy and were found to be 60% resistant to DNase I treatment. Biologically, the reassembled purified virions were found to partially regain both hemagglutinating activity and plaque-forming ability.