Association of herd management factors with colonization of dairy cattle by Shiga toxin-positive Escherichia coli O157.

Management factors in 36 Pacific Northwest dairy herds were evaluated for their association with the prevalence of Shiga toxin-positive Escherichia coli O157 (E. coli O157) in dairy cattle. The within-herd prevalence of E. coli O157 was estimated by bacteriological culture of fecal pat samples, collected monthly for 6 months (approximately 60 per visit), from heifer cattle. During the first visit to each farm, a management questionnaire was administered that covered a broad range of animal husbandry practices. On each subsequent visit, a brief questionnaire was administered to detect changes in management practices. A significantly higher prevalence of E. coli O157 was noted in herds that fed corn silage to heifers compared to herds that did not feed corn silage. More tentative associations of E. coli O157 prevalence were observed for weaning method, protein level of calf starter, feeding of ionophores in heifer rations, feeding of grain screens to heifers, and feeding of animal by-products to cows.

Multiple sources of Escherichia coli O157 in feedlots and dairy farms in the northwestern USA.

Samples from cattle, other domestic and wild animals, flies, feeds, and water-troughs were collected from 12 cattle farms and tested for Escherichia coli O157. E. coli O157 was isolated from bovine fecal samples on all 12 farms with a within herd prevalence ranging from 1.1% to 6.1%. E. coli O157 was also found in 1 of 90 (1.1%) equine fecal samples, 2 of 65 (3.1%) canine fecal samples, 1 of 200 pooled bird samples (0.5%), 2 of 60 pooled fly samples (3.3%), and 10 of 320 (3.1%) water-trough sample sets (biofilm and water). No E. coli O157 were isolated from 300 rodents, 33 cats, 34 assorted wildlife, or 335 cattle feed samples. Indistinguishable pulsed-field gel electrophoresis patterns of XbaI digested chromosomal DNA and Shiga toxin types were observed for bovine and water-trough isolates from two farms and for one equine and two bovine isolates from one farm.

A prolonged outbreak of Escherichia coli O157:H7 infections caused by commercially distributed raw milk.

A protracted outbreak of Escherichia coli O157:H7 infections was caused by consumption of unpasteurized ("raw") milk sold at Oregon grocery stores. Although it never caused a noticeable increase in reported infections, the outbreak was recognized because of routine follow-up interviews. Six of 16 Portland-area cases reported between December 1992 and April 1993 involved people who drank raw milk from dairy A. By pulsed-field gel electrophoresis (PFGE), E. coli O157:H7 isolates from these cases and from the dairy A herd were homologous (initially, 4 of 132 animals were E. coli O157:H7-positive). Despite public warnings, new labeling requirements, and increased monitoring of dairy A, retail sales and dairy-associated infections continued until June 1994 (a total of 14 primary cases). Seven distinguishable PFGE patterns in 3 homology groups were identified among patient and dairy herd E. coli O157:H7 isolates. Without restrictions on distribution, E. coli O157:H7 outbreaks caused by raw milk consumption can continue indefinitely, with infections occurring intermittently and unpredictably.

A longitudinal study of Escherichia coli O157 in fourteen cattle herds.

Escherichia coli O157 shedding in 14 cattle herds was determined by faecal culture at intervals of approximately 1 month for up to 13 months. The overall prevalence was 1.0% (113/10832 faecal samples) and 9 of the 14 herds were detected as positive. Herds positive 2 years previously (n = 5) had a higher prevalence of positive cattle (median = 1.9%) than herds which had been negative on a previous sampling (n = 8, median = 0.2%). Weaned heifers had a higher prevalence (1.8%) than did unweaned calves (0.9%) or adults (0.4%). For all herds the highest prevalence occurred in the summer months, which resulted in most of the positive faecal samples being collected on a minority of sampling visits.

The aliphatic oxidation of salmeterol to alpha-hydroxysalmeterol in human liver microsomes is catalyzed by CYP3A.

Salmeterol xinafoate (Serevent) is a long-acting beta2-adrenoceptor agonist, used in the treatment of asthma, that has bronchodilator and anti-inflammatory action. Salmeterol is extensively metabolized by aliphatic oxidation in humans, with the major metabolite being alpha-hydroxysalmeterol. The aim of this investigation was to identify the specific cytochrome P450 (P450) isoform or isoforms involved in the formation of alpha-hydroxysalmeterol in human liver microsomes. [14C]Salmeterol was incubated with a pooled sample (N = 19) of human liver microsomes in the absence or presence of selective chemical inhibitors of the major human P450 isoforms. One microM ketoconazole, a selective inhibitor of CYP3A, substantially inhibited the metabolism of salmeterol to alpha-hydroxysalmeterol. Disulfiram caused a small but consistent decrease in the amount of alpha-hydroxysalmeterol formed, possibly reflecting less than total selectivity for CYP2E1 under the conditions used. Other selective inhibitors had no significant effect on the metabolism of salmeterol. The rates of formation of alpha-hydroxysalmeterol in 10 individual liver microsomal samples showed an approximately 10-fold variation and were found to be highly correlated (r2 = 0.94; p < 0.001) with rates of metabolism of midazolam to 1'-hydroxymidazolam, a marker of CYP3A activity, in the same microsomal samples. No significant correlation was evident for the metabolism of salmeterol with levels of total P450 or other markers of human P450 activities in the same microsomal samples, thus indicating that the formation of alpha-hydroxysalmeterol is catalyzed predominantly by CYP3A. Insect cell microsomes that coexpressed human CYP3A and NADPH-P450 reductase were able to metabolize [14C]salmeterol to alpha-hydroxysalmeterol, thus confirming the role of CYP3A in catalyzing this reaction. The therapeutic dose of salmeterol is very low, so it is unlikely that any clinically relevant interactions will be observed as a consequence of the coadministration of salmeterol and other pharmaceutical agents that are metabolized by CYP3A.

Evaluation of pyrazole and ethanol induced S9 fraction in bacterial mutagenicity testing.

A major constitutive enzyme in the liver of the uninduced rat is cytochrome P450-2E1. This isozyme has been shown to metabolize a number of carcinogens, including low molecular weight nitrosamines and a number of compounds normally regarded as non-mutagenic in the Ames test, e.g. aniline, urethane and benzene. Using the standard induction procedures [Aroclor 1254 or a combination of phenobarbitone (PB) and beta-naphthoflavone (beta-NF)] the level of CYP2E1 in rat liver is actually suppressed and it has been suggested that this may account for the negative findings with these compounds in the Ames test. S9 fractions were prepared from rats pre-treated with pyrazole or ethanol (inducers of CYP2E1) and then used in the Ames test (or pre-incubation modification) with urethane, acetaminophen, aniline, benzene, procarbazine and N-nitrosopyrrolidine. Both pyrazole and ethanol induced S9 were superior to PB/beta-NF-S9 and uninduced-S9 for the activation of N-nitrosopyrrolidine, a known CYP2E1 substrate. However, there was no evidence of mutagenic activity with urethane, aniline, benzene, procarbazine or acetaminophen. As these compounds have demonstrated genotoxicity in vivo, additional important metabolic pathways must be required which are not present in rat liver S9 fraction.

Pharmacokinetics of idarubicin (4-demethoxydaunorubicin; IMI-30; NSC 256439) following intravenous and oral administration in patients with advanced cancer.

The plasma pharmacokinetics of idarubicin (4-demethoxydaunorubicin) were studied in 20 patients with advanced malignant disease after intravenous (21 occasions) and oral (14 occasions) administration. Idarubicin plasma concentrations were measured by high performance liquid chromatography with fluorescence detection. Pharmacokinetic parameters calculated for the intravenous plasma drug concentration, time data revealed a terminal half-life of 12.9 +/- 6.0 h (mean +/- s.d.), clearance 98.7 +/- 47.3 1 h-1 m-2 and volume of distribution 1533 +/- 536 1 m-2. A bi-exponential equation corresponding to a two compartment open model best fitted the data. Half-life and clearance were not significantly different following oral administration. Bioavailability of oral idarubicin was 0.29 +/- 0.20 (mean +/- s.d.). There was a wide range of bioavailability between and within subjects. Plasma concentrations of idarubicinol (the only metabolite detected) rapidly exceeded those of the parent drug, and exposure to this metabolite was greater than to the parent drug. The mean half-life of idarubicinol was not significantly different after i.v. (63.1 +/- 28.2 h) and oral (45.8 +/- 16.0 h) administration. Much larger amounts of this metabolite were formed following the oral route of administration. This may have implications for the clinical use of this drug as idarubicinol may have appreciable cytotoxic activity.

Digital wavefront measuring interferometer for testing optical surfaces and lenses.

A self-scanned 1024 element photodiode array and minicomputer are used to measure the phase (wavefront) in the interference pattern of an interferometer to lambda/100. The photodiode array samples intensities over a 32 x 32 matrix in the interference pattern as the length of the reference arm is varied piezoelectrically. Using these data the minicomputer synchronously detects the phase at each of the 1024 points by a Fourier series method and displays the wavefront in contour and perspective plot on a storage oscilloscope in less than 1 min (Bruning et al. Paper WE16, OSA Annual Meeting, Oct. 1972). The array of intensities is sampled and averaged many times in a random fashion so that the effects of air turbulence, vibrations, and thermal drifts are minimized. Very significant is the fact that wavefront errors in the interferometer are easily determined and may be automatically subtracted from current or subsequent wavefrots. Various programs supporting the measurement system include software for determining the aperture boundary, sum and difference of wavefronts, removal or insertion of tilt and focus errors, and routines for spatial manipulation of wavefronts. FFT programs transform wavefront data into point spread function and modulus and phase of the optical transfer function of lenses. Display programs plot these functions in contour and perspective. The system has been designed to optimize the collection of data to give higher than usual accuracy in measuring the individual elements and final performance of assembled diffraction limited optical systems, and furthermore, the short loop time of a few minutes makes the system an attractive alternative to constraints imposed by test glasses in the optical shop.

Analysis of Refractive Index Distributions in Cylindrical, Graded-Index Glass Rods (GRIN Rods) Used as Image Relays.

Cylindrical transparent media whose refractive index decreases with increasing cylinder radius have been investigated in connection with coherent light propagation in gas waveguides. Recently, graded index glass rods (trade named SELFOC rods) have been used as imaging devices. We report here on a geometrical optical study of graded index systems used for relaying images at unit magnification. We have found that two index distributions previously studied result in large image aberrations when the presence of skew rays is taken into account. We have derived an index distribution which is "ideal" for helical skew rays. Using ray tracing methods we have examined image aberrations for various index distributions and for various rod geometries. We find that (1) no one refractive index distribution can be "ideal" for both meridional and skew rays, (2) image resolution is generally low, reaching about 1000 spots per field, and (3) the optimal index distribution varies with the ratio of rod length to radius and the relative aperture and is intermediate between the helically ideal and the meridionally ideal distributions.