Biomedical subjects
S W Martin
Publications and source records attributed to S W Martin.
The six-day-old rat air pouch model of inflammation: characterization of the inflammatory response to carrageenan.
Inflammation was induced in the 6-day-old rat air pouch by injection of carrageenan. The model was characterized in terms of exudate volume, leucocyte influx, cell free protein, prostaglandin E2 levels, and granuloma formation. The time course of all these inflammatory markers, except prostaglandin E2, showed a 3-hr lag followed by a rapid increase to 8 hr. Thereafter, the rate of increase was much slower to 48 hr. Differential cell counts indicated a predominantly polymorphonuclear cell response (75%) during the first 48 hr. Prostaglandin E2 levels increased rapidly after a 3-hr lag, to a maximum of 440 +/- 140 ng/mL at 15 hr and thereafter quickly declined to 140 +/- 60 ng/mL at 21 hr. Prostaglandin E2 levels were the most sensitive inflammatory marker to (S+)-ibuprofen and were reduced dose dependently in the range 0.05 to 1 mg/kg. We have demonstrated the time course for duration of NSAID-induced reduction of prostaglandin E2 levels during inflammation in an individual animal. Rac-ibuprofen (0.1-1 mg/kg) reduced leucocyte influx at 3 and 5 hr, after which drug effects gradually diminished by 24 hr. Rac-ibuprofen at 1 mg/kg significantly reduced the volume of air pouch exudate recovered at 24 hr but had no effect on protein levels.
Return to oestrus after first insemination in sow herds (incidence, seasonality, and association with reproductivity and some blood parameters).
As no systematic study has been done to get an accurate estimate of the incidence of return to oestrus after first insemination in sows in the Netherlands, the objectives of this investigation were: 1) to obtain an estimate of the incidence of return to oestrus after insemination at the herd level; 2) to investigate the association between incidence of return to oestrus after first insemination and reproduction characteristics in order to get an impression of the economic importance of reproductive failure. These objectives were investigated by using the reproduction results of 240 swine breeding herds in the Southern Netherlands in 1987. This information was obtained from CBK plus computerized herd management records. The average incidence rate of return to oestrus after first insemination at a herd level was 16.9 per 100 first inseminations. The occurrence of return to oestrus after first insemination was distinctly higher in the insemination months July and August compared to the rest of the year. An increased incidence, with 10 returns per 100 first inseminations corrected for confounders in a multiple linear regression model, was associated with a decrease of approximately 0.3 live born piglets/sow/year. A prospective longitudinal study was started in 1988 and 1989 in 37 sow herds. Individual sows were monitored from weaning to first insemination, to the occurrence of return to oestrus, or not, after first insemination, and to farrowing. The investigation focused in particular on the relationship between return to oestrus after first insemination and seroconversion against porcine parvovirus (PPV) and Leptospira interrogans serovar bratislava (L. bratislava).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of chronic intravenous infusions of dopexamine and isoprenaline to rats on D1-, beta 1- and beta 2-receptor-mediated responses.
1. Rats received intravenous infusions of dopexamine, an agonist with selectivity for D1-dopamine receptors and beta 2-adrenoceptors (240 micrograms kg-1 h-1), isoprenaline, a beta 1- and beta 2-adrenoceptor agonist (40 micrograms kg-1 h-1) or vehicle (isotonic saline at pH 2.5) for 7 days via subcutaneously implanted osmotic minipumps. Tissues were then removed for determination of functional responsiveness to beta 1-adrenoceptor, beta 2-adrenoceptor and dopamine D1-receptor stimulation. 2. The beta 1-adrenoceptor-mediated responses of the spontaneously beating right atrium (increase in rate) and paced left atrium (increase in tension) showed significant reductions in sensitivity to isoprenaline following isoprenaline infusion. The EC50 values were significantly increased from 5.6 to 17.7 nM in right atria and from 7.4 to 27.1 nM in left atria. The maximum rate increase of right atria was also significantly less after isoprenaline infusion compared with controls (164.0 and 251.9 beats min-1, respectively) but the maximum tension responses of left atria were not significantly different. After infusion with dopexamine, however, there was no change in sensitivity of the left or right atria to beta 1-adrenoceptor stimulation by isoprenaline. 3. beta 2-Adrenoceptor-mediated relaxation responses to isoprenaline of the pulmonary artery, constricted with noradrenaline (6 x 10(-8) M), showed no significant difference in maximum response or EC50 in tissue from isoprenaline- or dopexamine-infused rats compared with vehicle-infused controls. beta 2-Adrenoceptor-mediated vasodilator responses were also examined in the kidney perfused with the thromboxane A2 analogue, U46619 (7.1 x 10(-8) M) to raise perfusion pressure. As with the pulmonary artery, there was no significant difference in ED50 or maximum response to isoprenaline in kidneys from isoprenaline infused animals compared with vehicle controls.4. The DI-receptor-mediated vasodilator responses to dopamine of the kidney perfused with U46619were reduced after infusion of rats with dopexamine. The maximum fall in perfusion pressure(16.0 mmHg) and ED50 value (5.2 microg) were significantly different from those after vehicle infusion(31.5 mmHg; 1.5 microg).5. These results show that functional responses mediated via beta1-adrenoceptors and DI-receptors are reduced by intravenous infusions of isoprenaline and dopexamine, respectively. In contrast, the beta2-adrenoceptor-mediated vasodilator responses of the pulmonary artery and kidney are not reduced by these agonists. Thus, under identical conditions, there appears to be selective down-regulation of peripheral beta 1- and D,-receptors, but not of beta 2-adrenoceptors.
Experimental determination of a drug targeting index for S(+)ibuprofen using the rat air pouch model of inflammation.
We have used the rat air pouch model of inflammation and S(+)ibuprofen as an experimental model system to enable the quantitative assessment of the pharmacokinetic determinants of site specific drug delivery. S(+)ibuprofen (50 & 1mg/kg) was administered directly into six day old air pouches immediately following the injection of the irritant carrageenan. Serial exudate and plasma samples were collected and analysed for ibuprofen by HPLC. The procedure was repeated following administration of S(+)ibuprofen (20 & 5mg/kg) intravenously. The parameters describing events in the air pouch and plasma indicated linear kinetics over the doses employed. The dose normalised AUCs were then used to formulate a quantitative measure of benefit for S(+)ibuprofen delivered directly to the air pouch. A Drug Targeting Index (DTI) was calculated from the ratio of AUC in the air pouch and plasma following direct intrapouch administration divided by the same ratio following intravenous administration and gave a value of 130. This pharmacokinetic measure of benefit represents the maximum advantage afforded by the site specific delivery of S(+)ibuprofen as the whole of the administered dose is delivered directly to the site of action.
Production practices, calf health and mortality on six white veal farms in Ontario.
A group of 4863 white veal calves reared on six commercial white veal farms in Ontario were followed through production to describe calf characteristics and production levels. Patterns of morbidity, mortality, and culling were investigated at the farm, room and individual level. The majority of the calves were male Holsteins, with approximately half originating from Ontario. The mean average daily gain for shipped calves over the entire production period was 1.1 kg/day (SE = 0.002). The overall percentage of calves receiving at least one individual treatment was 59%, with an average number of treatment days per calf of 3.3. The majority of calves receiving one or more treatment days were first treated between the fourth and seventh week of production. The mortality rate was 3.7%, and 5.1% of the calves were culled. Pneumonia was the largest single cause of death. Peak death and cull losses occurred during the seventh and eighth week of production.
Production indices, calf health and mortality on seven red veal farms in Ontario.
Production, morbidity, mortality and culling were investigated on seven commercial red veal farms in Ontario. The total number of calves included in the study group was 2251. The mean exit weight of marketed calves was 291 kg, with an average daily gain of 1.52 kg/day over the entire production period. The percentage of calves receiving one or more treatment days was 55%, with an average number of individual treatment days per treated calf of 3.9. An increasing number of treatment days, particularly up to eight days of treatment, was associated with decreasing average daily gain, and an increased probability of being lost from production due to death or culling. The percentage of calves which died during production was 5.4, with 0.8% of calves culled.
[Return to estrus following first insemination in sow herds (incidence and association with reproductivity and various blood parameters)].
As no systematic study has been done to get an accurate estimate of the incidence of return to oestrus after first insemination in sows in the Netherlands, the objectives of this investigation were: 1) to obtain an estimate of the incidence of return to oestrus after insemination at the herd level; 2) to investigate the association between incidence of return to oestrus after first insemination and reproduction characteristics to get an impression of the economic importance. These objectives were investigated using the reproduction results of 240 swine breeding herds in The Southern Netherlands in 1987, using their CBK plus computerized herd management records. The average incidence of return to oestrus after first insemination on a herd level was 16.9 per 100 first inseminations. An increase of incidence with 10 returns per 100 first inseminations, corrected for confounders in a multiple linear regression model, was associated with a decrease of approximately 0.3 liveborn piglets/sow/year. Thereupon individual sows were followed in 1988 and 1989 prospectively in 37 sow herds from weaning to insemination, returning to oestrus or not after first insemination to farrowing. The investigation focused in particular on the relationship between returning to oestrus after first insemination and incident infection with porcine parvovirus (PPV) and Leptospira interrogans serovar bratislava (L. bratislava). During a number of consecutive farm visits sows were blood sampled at weaning and again a blood sample was taken 6 weeks later. The final dataset that was analysed consisted of 161 animals that did not return to oestrus after first insemination and 158 animals that returned to oestrus after first insemination.(ABSTRACT TRUNCATED AT 250 WORDS)
Nonprostanoid prostacyclin mimetics. 5. Structure-activity relationships associated with [3-[4-(4,5-diphenyl-2-oxazolyl)-5- oxazolyl]phenoxy]acetic acid.
cis-[3-[2-(4,5-Diphenyl-2-oxazolyl)ethenyl]phenoxy]acetic acid (3) was previously identified as a nonprostanoid prostacyclin (PGI2) mimetic that potently inhibits ADP-induced aggregation of human platelets with an IC50 of 0.18 microM. As part of an effort to further explore structure-activity relationships for this class of platelet inhibitor and to provide additional insight into the nonprostanoid PGI2 mimetic pharmacophore, the effect of constraining the cis-olefin moiety of 3 into various ring systems was examined. Incorporation of the cis-olefin of 3 into either an oxazole (26) or an unsubstituted pyrazole (35) heterocycle provided compounds that are equipotent with progenitor 3. However, the oxazole 11f, which is isomeric with 26, inhibits ADP-induced human platelet aggregation in vitro with an IC50 of 0.027 microM, 6-fold more potent than 3, 26, or 35. These results suggest that the central oxazole ring of 11f is functioning as more than a simple scaffold that provides optimal stereodefinition for interaction with the PGI2 receptor. The nitrogen atom of the central heterocycle of 11f is postulated to engage in hydrogen-bond formation with a donor moiety in the PGI2 receptor protein, an interaction not available to 26 due to the markedly different topology. In support of this contention, the crystal structures of 11f and 26 contain strong intermolecular hydrogen bonds between the carboxylic acid hydrogen atom and the nitrogen atom of the central oxazole ring. Although 11f and 26 are exact isosteres and could, in principle, adopt the same molecular packing arrangement in the solid state, this is not the case, and the intermolecular hydrogen-bonding interactions in 11f and 26 are accommodated by entirely different molecular packing arrangements. Incorporation of the olefin moiety of 3 into a benzene ring provided a compound, 40, over 60-fold weaker with an IC50 of 11.1 microM. The affinities of 11f, 26, 31, 32, and 40 for the human platelet PGI2 receptor, determined by displacement of [3H]iloprost, correlated with inhibition of platelet function. The solid-state structures of 11f, 26, 31, 32, and 40 were determined and revealed that the more potent compounds 11f and 26 adopt a relatively planar overall topography. In contrast, the central phenyl ring and the phenoxy ring of the weakly active compound 40 are rotated by 53 degrees from planarity. The chemical shifts of the protons of the phenoxy rings of 3, 11f, 18, 26, 31, 32, and 40 suggest that in solution 3, 11f, 18, and 26 adopt a planar conformation while 40 does not.(ABSTRACT TRUNCATED AT 400 WORDS)
Dynamics and regulation of bulk milk somatic cell counts.
Somatic cell count (SCC) in milk is inversely related to dairy cow productivity and milk quality. In an effort to improve product quality, and indirectly farm productivity, regulatory limits on somatic cell counts have been established by many of the major dairy producing countries. The purpose of this paper was to assess the impact of regulations on bulk milk somatic cell counts in Ontario and to assist producers in meeting regulatory limits through development of prediction models. Through the use of a transfer function model, provincial SCC was found to have dropped by approximately 60,000 as a result of the reduction program. Limits of the regulatory program, seasonality and herd characteristics were found through time series cross-sectional models to have an impact on prediction of SCC at the farm level, but the major influence was historical SCC levels.
Estimating the number of clusters for the analysis of correlated binary response variables from unbalanced data.
Dominating the literature on sample size determination are papers concerned with observations collected from independent responses. We discuss in this paper, under the common correlation model for binary responses, the issue of estimating the number of groups when the sampling units are clusters of variable sizes.
Patterns of stillbirth and dystocia in Ontario cow-calf herds.
The association between a number of individual animal and herd level factors and calving problems in beef cows and heifers were examined. Data were from the 1987 calving season for a subset of 123 herds which maintained individual-animal records, from a sample of 180 randomly selected Ontario cow-calf herds. The median herd dystocia rate was 5.8% and 24.4% of herds had no dystocias. The median herd stillbirth rate was 2.8%, and 33.3% of herds had no stillbirths. Dystocias and stillbirths were much more common in heifers than in cows. Separate statistical models of dystocia and stillbirth for cows and heifers were created. Dystocia in cows was associated with calf sex, previous calving assistance and large breed type and birth weight. Variations in 1987 cow herd dystocia rates were associated with calving season, location and density, and the herd dystocia rate in 1986. Dystocia in heifers was associated with large breed type and calf birth weight. Herd-level management practices associated with increased heifer dystocia rates included breeding heifers to calve earlier than cows and rearing heifers together with the cow herd. Stillbirths for both cows and heifers were associated with calving assistance, particularly hard assistance. Herd-level management and other factors were unassociated with stillbirths.
Culling practices of Ontario cow-calf producers.
This study describes the distribution of herd culling rates for 123 Ontario cow-calf herds maintaining individual animal records. Associations between culling and factors at both the individual and herd level were examined. In addition, the relative importance of individual animal and herd level influences on culling were investigated. The following individual cow culling risk factors: nonpregnancy, age, weaning weight index, calf outcome, abortion, prolapsed vagina, prolapsed uterus, calving injury, lameness and mastitis or udder problems were significantly associated with culling (p less than 0.01). Two herd level factors were associated with increased culling rates: a higher than average proportion of heifers and a shorter than average calving season (p less than 0.01). The proportion of culling variation attributed to individual animal and herd level influences varied with model type. While simple models (one-way ANOVA) indicated that the herd variance component for culling was relatively minor, more complex models indicated larger herd-to-herd variability (mixed model ANOVA). Thus, it appeared that the probability of culling for a cow with a given set of risk factors depended to an important extent on manager decisions in the herd of origin.
Re: "Probability of introducing diseases because of false negative test results".
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Associations between dairy production indices and lipoarabinomannan enzyme-immunoassay results for paratuberculosis.
Data from an epidemiological study in Ontario, involving 304 dairy herds, were used to identify associations between selected production indices and lipoarabinomannan antigen serological test results for paratuberculosis (LAM-ELISA). Analyses were conducted at both the herd and individual cow levels of organization. After analytically controlling for management and cow factors in the respective regression models, positive serological paratuberculosis status (as defined by the LAM-ELISA test), was associated with higher milk somatic cell counts at both the herd average (p less than 0.01), and individual cow levels of organization (p less than 0.0001). In contrast, LAM-ELISA test results were consistently not associated with calving intervals in either the herd average or individual cow level analyses. Associations between LAM-ELISA results and milk production were inconsistent. No associations were found at the herd level of organization, and LAM-ELISA results were not associated with a change in breed class average (BCA) for milk, between the previous and the most recent lactations of individual cattle. However, at the individual cow level, LAM-ELISA results were positively associated with higher milk production as measured by the current BCA (p less than 0.05), and individual cow average kg of milk produced per year of life since two years of age (p less than 0.0001).
Endometrial biopsy in Holstein-Friesian dairy cows. I. Technique, histological criteria and results.
Endometrial biopsies were taken for histological assessment from 97 cows which calved in a commercial dairy herd between April and August 1984. Sixty-two cows were biopsied at both day 26 and 40 postpartum, 23 cows at only day 26, and 12 at day 40 only. Subjective and quantitative histological criteria were assessed. Ninety-five percent of biopsies were adequate for at least subjective assessment. The distribution of criteria within each horn-day category, as well as combined readings by day and by gravid or nongravid horn were computed and significant differences noted. There was more severe inflammation and more segmented cells at day 26 than 40 postpartum, and in the gravid compared to the nongravid horn. The distribution patterns for the criteria examined provide an overview of histological characteristics in this group of postpartum cows.
Endometrial biopsy in Holstein-Friesian dairy cows. II. Correlations between histological criteria.
Endometrial biopsies were taken for histological assessment from 97 cows which calved in a commercial dairy herd between April and August 1984. The main objectives of this study were to analyze the interrelationships among histological criteria and to identify a shortlist of histological parameters to be included in subsequent analysis of associations with results of bacteriological culture, clinical findings and reproductive performance. Epithelial height and segmented cell counts were highly correlated within biopsy, between horns and between days. Subjective assessment of inflammation in the epithelium and/or stratum compactum generally identified biopsies which had any inflammation present. Cows which had inflammation in a biopsy from day 26 were likely to show inflammatory changes at day 40. Quantitative and subjective assessments of gland number, dilation and fibrosis were highly correlated. There was a positive association between the number of cross sections and the diameter of glands, and both of these criteria were negatively correlated with fibrosis and inflammatory changes. There may be different functional significance of the same histological finding at a different number of days postpartum.
Endometrial biopsy in Holstein-Friesian dairy cows. III. Bacteriological analysis and correlations with histological findings.
This study examines the results of bacterial culture from 159 endometrial biopsy samples from 97 commercial dairy cows and correlations between bacteriological and histological findings. Bacteria were isolated from approximately 80% of biopsies taken at day 26 and day 40 postpartum. Eleven percent of biopsies were positive for both aerobic and anaerobic culture. Streptococci, Escherichia coli and Actinomyces pyogenes were the most common isolates. Isolation of A. pyogenes from a biopsy at day 26 was positively correlated with isolation of anaerobic bacteria and segmented cell inflammation in the same biopsy, and with subsequent isolation of A. pyogenes at day 40. There was a strong association between isolation of A. pyogenes and anaerobes at day 26 with increased uterine lesions at day 40. Isolation of alpha hemolytic streptococci (AHS) was negatively correlated with isolation of A. pyogenes and with inflammation. Actinomyces pyogenes and AHS showed opposite associations with mononuclear cell inflammation and lymphocytic foci.