Point of Technique. A training model for transurethral injection therapy for stress incontinence.
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Biomedical subjects
Publications and source records attributed to S W Martin.
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OBJECTIVE: To examine the potencies of the potassium-channel openers (KCOs) levcromakalim and YM934 as relaxing agents on human detrusor and human mesenteric artery smooth muscle, and to determine their bladder-vascular selectivity in vitro. MATERIALS AND METHODS: Strips of human detrusor muscle and mesenteric artery (with the endothelium removed) were set up in physiological salt solution and the tension developed by the tissues recorded. Tissues were precontracted with a concentration of carbachol (detrusor) or phenylephrine (artery) which caused 80% of maximal contraction, and relaxation responses to levcromakalim and YM934 were then obtained. RESULTS: Both KCOs caused relaxation of the bladder detrusor muscle and the mesenteric artery. Maximal responses, when plotted as a percentage of the precontraction, were greater for both KCOs in the bladder muscle than the artery, but the differences were small and not statistically significant. The sensitivity (drug potency) of the detrusor muscle to the KCOs was more than twice that of the artery but this selectivity was only statistically significant for YM934. CONCLUSIONS: Only minor bladder-vascular selectivity for levcromakalim and YM934 could be detected in vitro. This suggests that neither drug would be tolerated clinically, although the results suggest that further development of bladder-selective KCO agents appears feasible.
A randomized controlled field study of selective dry cow therapy with 686 cows allocated to two control groups (sampling only or placebo) or two therapy groups was used to screen for possible factors associated with penicillin-resistant strains of Staphylococcus aureus after the dry period. Therapy was given either as a total dose of 400,000 IU of penicillin and 100 mg of neomycin per infected quarter as dry cow preparation or as a total dose of 1.2 million IU of penicillin and 1200 mg of dihydrostreptomycin per infected quarter as a lactation formula. Success cows had all quarters identified as being free of penicillin-resistant strains of Staphylococcus aureus both at calving and at 30 +/- 17 d after calving. Failure cows were those having penicillin-resistant strains of Staph. aureus in any quarter at both or one of these two samples after the dry period. Using logistic regression, four variables were found to be associated with penicillin-resistant strains of Staph. aureus after the dry period. These included the identification of penicillin-resistant strains of Staph. aureus either at 45 +/- 32 d before drying off and at drying off, treatment for acute clinical mastitis at least once during the previous lactation, the weighted SCC of all cows' milk by daily milk yield within the herd, and therapy in the lactation formula compared with the two control groups. Our finding that the use of lactation formula increases the risk of resistance development is contradictory to present arguments underlying Norwegian dry cow therapy strategy.
One of the impacts of disease is its effect on milk production. In the present study the effect of an outbreak of bovine herpesvirus type 1 on milk production at the herd level of certified bovine herpesvirus type 1-free dairy farms was modeled. The objective was to study several linear models to quantify the effects of a bovine herpesvirus type 1 outbreak on milk production accounting for the repeated measurements and incorporating our assumptions about the most likely duration of effects of this virus. Because milk production is measured at regular intervals, the data consisted of repeated measurements at the herd and cow levels. A marginal model, a subject-specific random-effect model, and a transition model were developed. The effect of a bovine herpesvirus type 1 outbreak was statistically significant in the random-effect model, and this model fitted the investigated farms best. However, a transition model might be a better model for generalizing the results to the whole population of Dutch dairy farms. The effect of a bovine herpesvirus type 1 outbreak on milk production derived from the random-effect model amounted to, on average, a loss of 0.92 kg of milk per cow per day during a period of 9 wk. The milk production loss varied from almost none to 2 kg of milk per cow per day. This reduction resulted in an average loss of Dfl 372 (Dfl1 = $US $0.50) with lower and upper confidence limits of, respectively, Dfl 12 and Dfl 730 per bovine herpesvirus type 1 outbreak.
Discriminant factors for the elimination of major pathogens (mainly Staphylococcus aureus and Streptococcus dysgalactiae) were identified from a randomized, double-blind, field study on dry cow therapy. From an original study of 686 cows, 269 fulfilled the criteria for this analysis: 93 from the control group, 83 from group C (treated with Benestermycin vet. "LEO") and 93 from group D (treated with Leocillin with Dihydrostreptomycin vet. "LEO"). A "success" cow was defined as a cow that had all quarters healthy in two tests after dry period. Isolation of a major pathogen (mainly Staph. aureus or Strep. dysgalactiae) in any quarter in both samples after the dry period was defined as "failure." Better elimination was associated with short-acting preparations (therapy D) rather than with long-acting therapy C (odds ratio = 0.32), as was a smaller mean value of the last three composite milk somatic cell counts (CMSCC) before dry cow therapy. Cows with a major pathogen in the right hind quarter at drying off or at least one case of acute clinical mastitis during the previous lactation were more likely to have a major pathogen in the next lactation (odds ratio = 4.1 and 3.6, respectively). Young cows without major pathogens at drying off should not be recommended for dry cow therapy, and cows with high CMSCC should be considered for culling if their profiles also show previous acute clinical mastitis in combination with generally high CMSCC and low cure rates in the herd.
Data recorded in a herd health management system were obtained from 32 registered Holstein dairy herds from British Columbia. Frequencies of disease were described, and the effect of herd, age, year, season, and the interrelationships between diseases within a lactation on the occurrence of disease were evaluated. Lactational incidence rates were computed for diseases with a short period of risk (ie, udder edema, milk fever, retained placenta, metritis, displaced abomasum, and ketosis), whereas for diseases with a longer period of risk (ie, cystic ovaries, mastitis and stable footrot), incidence densities were calculated. Overall, the disease incidence was low and showed an increase in frequency by year, which we attributed to more observing and complete recording by the owner, rather than an actual increase in disease incidence. Most diseases occurred early in lactation and their frequency increased with lactation number; the exception was udder edema, which occurred mainly during the first 2 lactations. An informal path model of disease interrelationships was made conditional on herd. Based on the results we inferred 2 independent pathways: one started by udder edema, and the other by milk fever. Udder edema was directly associated with mastitis occurrence from 0 to 30 d in lactation, metritis, and cystic ovaries. Mastitis from 0-30 d in lactation increased the risk of both mastitis from 31-150 d in lactation and cystic ovaries. Both of these increased the risk of late lactation mastitis. Milk fever was directly related with displaced abomasum, which increased the risk of footrot. In general, diseases that occurred in early lactation tended to increase the risk of other diseases later in lactation.
The effects of in vitro incubation of rat isolated left atria, pulmonary artery rings, and aortic rings with isoprenaline (10(-6) M for 6 h) were examined to compare the degree of desensitization of beta1- and beta2-adrenoceptor-mediated functional responses. The experimental protocols were carefully controlled to exclude influence from persistence of agonist in the tissues after the prolonged exposures, time-dependent changes in tissue sensitivity, and the methods of plotting the data. Concentration-response curves for isoprenaline were constructed before incubation with isoprenaline and, after washout during 1 h, a second curve was obtained. Two protocols were employed: firstly, the preincubation curve was constructed to ensure that a maximum response was obtained (>10(-6) M) and, secondly, the preincubation curve was constructed to a maximum isoprenaline concentration of 10(-6) M. Preincubation curves were corrected for time-dependent changes in sensitivity from sham-incubation control experiments. There was significant desensitization of the beta1-adrenoceptor-mediated positive inotropic responses of the left atria, using both protocols, seen as rightward shifts (dose ratios: 4.48 +/- 1.12 and 8.39 +/- 2.3) of the concentration-response curves and depression of the maximum responses (77.0 +/- 3.2 and 60.8 +/- 5.5%). In contrast, the beta2-adrenoceptor-mediated relaxations of the noradrenaline-constricted pulmonary artery and aorta did not display a significant loss of sensitivity. When the relaxation responses were plotted as a percentage of the noradrenaline-induced tone, there was no significant rightward shift of the concentration-response curves in the pulmonary artery (dose ratios: 2.82 +/- 1.33 and 2.24 +/- 0.62) or aorta (dose ratios: 1.43 +/- 0.62 and 1.31 +/- 0.27) and thus no desensitization.
Blood samples from 32 groups of calves (n = 700) were taken on arrival and after 28-35 days at the feedlot. Eleven groups were housed in feedlots in Ontario, and 21 groups in feedlots in Alberta. Serum antibody titers to bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza virus type 3 (PIV-3), infectious bovine rhinotracheitis virus (IBRV), Mycoplasma dispar and M. bovis, plus data on bovine corona virus (BCV) from a previous study were investigated for their association with the risk of bovine respiratory disease (BRD), and with 28-day weight change, both before and after controlling for titers to Pasteurella haemolytica and Haemophilus somnus. Exposure to IBRV and M. bovis was infrequent, and although exposure to PIV-3 was more common, none of these agents had important associations with BRD. Higher titers to BVDV, BRSV, and BCV on arrival were associated with reduced risks of BRD and increased weight gains. However, there was some variation in these relationships and higher arrival titers to BVDV and BRSV in a subset of the calves were associated with increased risks of BRD. Titer increases to BVDV were associated with a higher risk of BRD and lower weight gains. Titer increases to BRSV were not usually associated with the occurrence of BRD, but titer increases to BRSV in a subset of calves that were vaccinated against BRSV, on arrival, were associated with an elevated risk of BRD. Of all the agents studied, BVDV had the most consistent associations with elevated risk of BRD and lower weight gains. Higher BRSV arrival titers were related to lower risk of BRD and higher weight gains; in some instances titer increases to BRSV were associated with higher BRD risk. Higher titers to BCV on arrival were related to reduced risks of BRD. Practical ways of adequately preventing the negative effects of these agents are still needed.
The objective of this study was to illustrate methods for investigating factors associated with seasonality, using milk-component production as an example. Milk-protein and fat percentages showed a seasonal pattern; percentages were lowest during June and July and highest in October and November. Graphical methods were used to compare herd calving patterns to seasonal production patterns and spectral analysis were used to compare seasonal production patterns between farm groups with different management practices. For the comparison of seasonality of production and herd calving patterns, data was obtained from archival records for all cows enrolled in Dairy Herd Improvement (DHI) milk recording in Ontario, Canada from 1990 to 1994. For comparisons of seasonality and management practices, monthly protein and fat percentages were obtained from the Dairy Farmers of Ontario from March 1985 to July 1994. Management information was obtained from responses to questionnaires completed by 364 dairy producers in Ontario. Graphical analyses provided a visualization of the relationship between herd calving patterns and seasonality of production-however, graphical methods alone did not allow statistical inferences to be made. Spectral analyses provided a formal statistical test of the null hypothesis of no association between an independent variable (farm management type) and seasonal production pattern in the data over time, provided that the outcome followed the same seasonal pattern regardless of covariate levels under the null hypothesis.
Associations between protein production and individual-cow reproductive performance, health, and culling were investigated in a 2-year observational study involving a convenience sample of 75 Ontario, 5 Alberta, and 3 Nova Scotia dairy farms. Protein production was defined by 305-day lactation protein yields and by estimated breeding values for protein yield. After controlling for the level of milk production, herd, parity, breed, and season of calving, there were no significant associations between either measure of protein production and days open or days to first breeding. The only associations between protein production and disease were small positive associations between the estimated breeding value for protein yield and cystic ovaries and mean lactation somatic cell count. The risk of culling, after controlling for the level of milk production, was negatively associated with previous-lactation 305-day protein yield for parity three animals only. The estimated breeding value for protein yield had a small negative association with the overall risk of culling, although the associations were not significant for individual lactations.
The objective of this paper was to illustrate the dependence of the kappa statistic on the underlying population prevalence of a measured outcome, and the related difficulties in interpreting kappa values for assessing the repeatability of survey data. An example was taken from a test-retest study of the repeatability of a questionnaire administered to dairy producers in Ontario, Canada. Ten producers completed two questionnaires, which contained numerous identical questions. Kappa was used to assess repeatability between the questionnaires for questions with responses which were measured on a dichotomous scale. The magnitude of the kappa statistic is shown to be a function of the prevalence of the trait measured by a question as well as the number of discordant responses.
Associations between stage of lactation, cow characteristics, and protein production were evaluated using data from a 2-year period on 75 Ontario, 5 Alberta, and 3 Nova Scotia dairy farms. Individual-cow protein production was defined by 305-day protein yield and by the estimated breeding value for protein yield. Lactation curves for average daily protein yield were computed by parity, breed, and season of calving. Mean protein yield was highest in early lactation. However, there was no pronounced peak in daily protein yield. Parity was positively associated with 305-day protein yield and negatively associated with the estimated breeding values for protein yield. First-calf heifers had lower protein yields in early lactation and a slower rate of decline in protein yield in late lactation, as compared to later parity cows. Holstein cows had higher unadjusted protein yields and lower protein yields after adjusting for milk yield than other breeds. Holstein cows had significantly higher protein yields early in lactation compared to other breeds, but the rate of decline in protein production in late lactation was also greater. Season was associated with 305-day protein yield; the highest protein yields occurred in cows calving in the fall and winter months, but these cows had the greatest rate of decline in protein production in late lactation.
1. Peroxynitrite is a short-lived and damaging oxidant that forms rapidly from the reaction of superoxide with nitric oxide. 2. In 1990, Joseph Beckman proposed that peroxynitrite contributed significantly to pathological oxidative stress in living tissues, and subsequent evidence strongly supports this proposal. 3. In this review, we outline the properties of peroxynitrite and discuss how it can affect biological systems and contribute to human pathologies.
Immunogenicity, pharmacokinetics, and therapeutic efficacy of three novel dimeric soluble tumor necrosis factor (TNF)-receptor I constructs [TNF-binding protein (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were challenged with a lethal Escherichia coli bacteremia. The three constructs differed only in the number of extracellular domains of the TNF receptor I and were dimerized with polyethylene glycol. Although all three constructs had generally similar pharmacokinetics when administered to a naive animal, they differed quantitatively in their immunogenicity. Antibodies were detected more frequently, and titers were significantly higher (P < 0.05) in both healthy and septic baboons that received the 4.0-domain TNF-bp construct, compared with animals receiving the 2.6-domain construct. When the TNF-bp constructs were administered a second time (21 days later), the half-lives of the three constructs were significantly shorter in animals that had an antibody response after the first injection. In contrast, all three TNF-bp constructs were equally effective at improving outcome, blocking a systemic TNF-alpha response, and attenuating the cytokine responses when administered at a dose of 1.0 mg/kg body wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicity of TNF-bp constructs can be altered by changing the number of functional domains, without affecting their capacity to neutralize TNF-alpha and to abrogate TNF-mediated pathology.
Intracranial and intraspinal ependymomas are uncommon tumors of the central nervous system. These tumors have a variety of imaging characteristics, some of which are fairly specific for ependymoma. We discuss the MRI features of ependymomas for each of the typical locations within the neuraxis, and provide MR imaging examples.
A total of 4368 first lactation records for Holstein cows from 30 herds was used to estimate genetic parameters for yield, conformation traits, and the binary coded disease traits of udder edema, milk fever, retained placenta, metritis, displaced abomasum, ketosis, cystic ovary, mastitis, and lameness. Data on health, parentage, and yield came from an on-farm program for record keeping and management. Test day production data were obtained from British Columbia DHI. Type classification data were received from the Holstein Association of Canada. Heritabilities of disease traits were low ranging from 0 to 0.05. Exceptions were lameness (0.16) and ketosis (0.39). Correlations of disease traits with 305-d milk yield and of selected type traits with retained placenta, displaced abomasum, mastitis, and lameness were estimated. Phenotypic correlations did not substantially differ from 0 except for the correlation between lameness and rear leg set (0.37). Genetic correlations between disease traits and milk yield were mostly positive (0.02 to 0.44). Only retained placenta had a negative genetic correlation with milk yield (-0.28). Genetic correlations ranged from 0 to 0.37 between udder conformation traits and mastitis, from -0.38 to 0.09 between leg conformation traits and lameness, and from -0.11 to 0.38 between rump conformation and retained placenta. The results suggest that selection based solely on yield may increase the incidence of disease. Selection on conformation traits can help reduce the incidence of disease, although genetic correlations are low.
The association between bovine respiratory disease (BRD) and antibody titers to bovine coronavirus (BCV) was studied in 604 calves (19 different groups in 4 different feedlots from 2 provinces). Almost all calves had antibody titers on arrival in the Alberta feedlot and 82% of the calves had an antibody titer on arrival at the Ontario feedlots; titers in calves in Alberta were almost twice as high as those in calves in Ontario. The incidence of infection, in the first mo after arrival as judged by seroconversion, ranged from 61% to 100%; titer increases were much greater in calves in Ontario feedlots. Titer variables were not significantly related to BRD, except on a within-group basis (group was a confounding variable for BCV-BRD associations). Given control of group effects, calves with an antibody titer on arrival appeared to be protected against BRD for the first 28 d in the feedlot, and the association was reasonably linear over the range of titers. Each titer unit on arrival decreased the risk of BRD by about 0.8x (odds ratio). Titer change was not strongly related to the risk of BRD and the relationship was not linear over the range of titer changes. Titer change was strongly and negatively correlated with titer on arrival, and titer change was not significantly related to BRD in the presence of arrival titers. Arrival titer retained its relationship with BRD in the presence of titer data for other putative pathogens. Each higher unit of titer to BCV on arrival increased the 28-day weight gain (controlling for group, initial weight and the occurrence of BRD) by slightly more than 1 kg. Titer change was associated with decreased weight gain, when initial titer was not in the model. The lack of a linear or multivariable association between BCV titer change and BRD, and weight gain, may indicate that BCV is not a major pathogen; or, its lack of significance may merely be due to its strong correlation with arrival titer. Given the associations found in this study, particularly the interprovincial differences in arrival titers, more and different approaches to studying the possible effects of BCV on BRD are in order.
Serum samples were obtained from 602 calves (from 19 groups in four feedlots: three in Ontario, and one in Alberta) upon arrival at the feedlot and 28 d later. Of these calves, 202 developed bovine respiratory disease (BRD) and 400 did not develop BRD. Based on high antibody titers noted upon arrival, we infer that most calves were exposed to Haemophilus somnus prior to arrival at the feedlot. Within a group, calves with high titers on arrival had a reduced risk of developing BRD later. Most calves did not experience titer increases after arrival; however, calves that had stable or increasing titers had a relatively low risk of contracting BRD. The calves at greatest risk of BRD were those with titers on arrival of less than 6.8 units and subsequent titer decreases of more than 1 unit. The effects of both the titer on arrival and the titer change after arrival were stable when the serologic effects of a number of viruses and Mycoplasma agents were considered. Neither antibody titer on arrival nor titer change was related to weight gain differences among calves. Calves with BRD or calves with lower weight on arrival had decreased weight gains in the first 28-day feeding period. The high titers on arrival may have protected most calves against further infection with H. somnus. However, since the calves that developed BRD had large titer increases to a number of viruses and to Pasteurella haemolytica, while having decreased antibody titers to H. somnus, we infer that the existing antibodies were "used up" in combatting the agents, including H. somnus, which may have "caused" the BRD. Calves which were able to increase their antibody levels to H. somnus tended to have a reduced risk of BRD.