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Biomedical subjects

S W Martin

Publications and source records attributed to S W Martin.

At least 73 records · Page 4Linked to original sources

Degradation-induced transmission losses in silica optical fibers.

BACKGROUND AND OBJECTIVE: The interaction of surgical optical fibers with tissue has been studied. STUDY DESIGN/METHODS AND MATERIALS: Fibers (600 microns) were lased in chicken and beef tissue using a Nd:YAG laser from 5 to 50 W in both cw and pulsed modes. RESULTS: With longer lasing and higher power, larger transmission loss and degradation (burn-in) of the fiber tip, occurred. This degradation converts the Nd:YAG laser power to heat and leads to further energy loss. During contact lasing, tissue and blood adhere to the fiber tip surface limiting laser transmission, desiccating, and eventually destroying adhering tissues. Such tissue residues create high power densities and temperatures at the tip, which then cause a variety of degradation processes to be initiated. CONCLUSION: "Burned-in" fibers do not photocoagulate; rather they incise tissue. With continued lasing, thermal shock, chemical, and mechanical breakdown of the fiber leads to failure of the fiber tip and the spalling of glass fragments into the tissue bed.

Animals↗

Calf health in cow-calf herds in Switzerland.

In 1993, an observational study was initiated to provide general information on animal health in extensive beef farms, to estimate disease frequency and the economic impact of calf diseases and to identify risk factors related to health and weight gain. The longitudinal study was conducted from fall 1993 until winter 94/95 and included 100 farms in western Switzerland. The basic concept was to follow one generation of calves on these farms and record all events concerning animal health from birth to weaning. The study population included 1270 calves (most were Angus crossbreds). Farm-management data were collected with a questionnaire conducted on the farm. Birth and weaning weights were obtained from the beef cattle breeding association. Clinical diagnoses and treatment costs were provided by the farm veterinarians. Two thirds of the dead calves were submitted to a complete postmortem examination. Fifty-three percent of the farms in the study were primary type income farms while 47% were secondary type income farms. Thirty-eight percent of the farms were situated in the lower areas of Switzerland, 14% in the prealpine foothills, the remaining 48% were located in mountain areas. Preweaning calf mortality was 5%. The main causes of calf deaths were respiratory diseases and digestive disorders. Twenty-two percent of the calves were treated at least once by a veterinarian; 36% of the treatments administered by the veterinarian were applied because of diarrhea, 27% because of respiratory diseases. Disease incidence was highest during the months of November, December and January. The association of disease and potential farm-level risk factors was analysed using chi 2-statistics and multivariable regression methods including generalized estimating equations to adjusted for herd effects. Specific risk factors for disease were not identified. Treatment for disease was not associated with 250-day standardized weight gain.

Aging↗

The association between the bovine tuberculosis status of herds in the East Offaly Project Area, and the distance to badger setts, 1988-1993.

The proximity of farms to badger setts was compared between farms that had experienced a tuberculosis breakdown and those that had not, over the 6 year period from 1988 to 1993. The data were derived from a badger removal study conducted in East Offaly County in the Republic of Ireland. Badger removal began in 1989 and continued through 1993; by the end of 1990, approximately 80% of all badgers caught in the 6 year period had been removed. All badgers were examined, grossly, for evidence of tuberculosis. Tuberculosis status of the approximately 900 study herds was based on the results of the single intradermal comparative skin test and/or lesions of bovine tuberculosis. All herds were tested at least once annually. The number of herds experiencing bovine tuberculosis declined over the period, particularly in the years 1992 and 1993. The data on farm and badger sett location were stored and analysed, initially, in a geographical information system. Owing to the badger removal programme, the distance between the barn yard of a typical farm and the nearest occupied badger sett increased, by about 300 m year-1, and by about 600 m year-1 to the closest infected sett. In bivariate analyses, in the years 1988 and 1989, the risk of tuberculosis declined with increasing distance to a badger sett containing one or more tuberculous badgers. In multivariable logistic regression analyses, year and the average number of cattle tested per farm per year were controlled. A second identical analysis was conducted to control for the repeated observations on the same herds using generalised estimating equations. In both analyses, the risk of a multiple reactor tuberculosis breakdown decreased for herds at least 1000 m away from an infected badger sett, and increased as the number of infected badgers per infected sett increased. Despite the significantly reduced risk of a breakdown with increasing distance to infected badger setts, the relationship was not strong (sensitivity and specificity of the model in the low 70% range) and explained only 9-19% of tuberculosis breakdowns.

Animals↗

Evaluation of a bulk-milk ELISA test for the classification of herd-level bovine leukemia virus status.

The results of a commercial bulk-milk enzyme-linked immunosorbent assay (ELISA) test for herd-level bovine leukemia virus (BLV) status were compared to results obtained from individual agar-gel immunodiffussion (AGID) testing on sampled cattle. A positive herd was defined as a herd having one or more AGID-positive animals. The estimated true herd status was based on the sensitivity and specificity of the AGID test and the number of cattle sampled per herd. Ninety-seven herds were used, with a mean of 13 cows sampled per herd. The AGID test indicated an apparent herd prevalence of 70.1%. After accounting for the number of cows sampled and the sensitivity and specificity of the AGID test, the estimated true herd prevalence of BLV was 52.3%. The ELISA test identified 79.4% of herds as positive for BLV, and had an apparent sensitivity and specificity of 0.97 and 0.62, respectively. However, after accounting for the sensitivity and specificity of the AGID test in individual animals, the specificity of the ELISA test was 0.44. The ELISA test was useful for identifying BLV-negative herds (i.e., ruling out the presence of BLV infection in test negative herds). With the moderately low specificity, herds identified as positive by the ELISA test would require further testing at the individual or herd level to definitively establish their BLV status.

Animals↗

Associations between farm management practices, productivity, and bovine leukemia virus infection in Ontario dairy herds.

The objective of this study was to investigate the associations between herd-level bovine leukemia virus (BLV) status and herd-level management and production variables. The study population consisted of 1330 cows sampled from 102 Ontario dairy herds. The individual-cow prevalence of BLV infection in the population (based on AGID testing) was 23%, with 69.6% of herds having one or more positive animals. The herd-level explanatory variables were divided into two datasets containing winter housing variables and all non-seasonal variables, and summer housing variables and all non-seasonal variables. In both datasets, multivariable analyses found a negative association between herd-level milk production and BLV status, and positive associations between weaning age and purchasing animals from outside sources, and BLV status. Housing pre-weaned calves in hutches or separate calf buildings in either season was associated with an increased risk of BLV. The model containing winter housing variables also included positive associations between contact with older animals and BLV status, and between BLV status and the facilities used to house dry cows in the winter.

Aging↗

Quantitative study of the short range order in B2O3 and B2S3 by MAS and two-dimensional triple-quantum MAS 11B NMR.

Two-dimensional multiple-quantum magic angle spinning (MQMAS) NMR and MAS NMR of 11B at various magnetic fields, were applied to elucidate the structure of vitreous (glassy) boron trioxide (v-B2O3), vitreous boron trisulfide (v-B2S3) and crystalline boron trisulfide (c-B2S3). These techniques, when combined with computer simulations of the resulting spectra, provide the isotropic chemical shifts and the quadrupole parameters, as well as a quantitative measure of the intensities of various boron resonances. The MAS NMR of v-B2O3 produced overlapping anisotropic lineshapes corresponding to the -1/2<-->1/2 transition in two distinct types of BO3 units with 3(+/-0.08):] intensity ratio. A combination of MAS and the multiple-quantum method resulted in a better resolved, isotropic 11B spectrum of v-B2O3. A remarkable enhancement of resolution of the MQMAS NMR proved instrumental in finding and identifying various impurities present in v-B2S3 and c-B2S3. In addition to the resonances from boron in two types of BS3 groups, four other structural units, BOS2, BO2S, BO3 and BS4, were elucidated from the spectra of vitreous and crystalline samples. The effects of various experimental parameters, such as the magnitude of the B0 and B1 fields, on the resolution of the MAS and MQMAS techniques are also shown.

Algorithms↗

Relaxant effects of potassium-channel openers on normal and hyper-reflexic detrusor muscle.

OBJECTIVE: To compare the effects of the potassium-channel openers, levcromakalim and YM934, in isolated human detrusor muscle from normal and hyper-reflexic bladders. MATERIALS AND METHODS: Strips of human detrusor muscle from normal and hyper-reflexic bladder were pre-contracted with carbachol and the potassium-channel openers (0.1-0.3 mumol/L) were added cumulatively to the organ baths. Other strips were field-stimulated at frequencies producing 25% and 75% of the maximum response to field stimulation. Contractions could be abolished by atropine (10 mumol/L) and tetrodotoxin (1 mumol/L). RESULTS: The hyper-reflexic bladder was significantly more sensitive to carbachol than the normal bladder but the maximum response was significantly lower in the hyper-reflexic tissue. There was no significant difference between the potency of the potassium-channel openers in normal and hyper-reflexic detrusor muscle. Hyper-reflexic bladder was significantly more sensitive to electrical field stimulation than was normal bladder: maximum responses to field stimulation were not significantly different. Concentration-response curves for the potassium-channel openers were displaced to the left in hyper-reflexic bladder at both 25% and 75% maximum frequencies: however, only with levcromakalim at 75% of the maximum frequency was the shift significant. CONCLUSION: The greater sensitivity of hyper-reflexic bladder to carbachol and field stimulation supports existing evidence for post-junctional supersensitivity in detrusor instability. The results of this study also suggest that there are no appreciable changes in KATP channel function in the unstable bladder.

Benzopyrans↗

Associations between winter herd management factors and milk protein yield in Ontario dairy herds.

A questionnaire was used to investigate associations between farm management practices in winter and milk protein yield. The questionnaire was completed by 500 dairy producers in Ontario, Canada in March 1994. A high positive correlation (0.96) existed between herd mean for protein yield per day per cow and herd mean for milk yield per day per cow. Therefore, most management practices that were associated with the farm mean for protein yield per day per cow were also associated with the farm mean for milk yield per day per cow. After adjustment for farm mean milk and fat yields, farms that housed dry cows as a separate group had higher mean protein yields than did herds that housed dry cows with the milking herd or the bred heifers. A positive association existed between herd mean for days of lactation and protein yield. Because of the correlation between milk and protein yields, these associations were of small magnitude. Thus, the potential benefit of progressive practices in herd management are primarily related to increased yields of milk and milk components in general rather than specifically to an increase in protein yield.

Animal Feed↗

Pharmacokinetics and metabolism of the novel anticonvulsant agent N-(2,6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) in rats and humans.

N-(2,6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) belongs to a new series of experimental anticonvulsants related to lidocaine. This study was undertaken to understand the pharmacokinetics and metabolism of D2624 in rats and humans, with emphasis on the possible formation of 2,6-dimethylaniline (2,6-DMA). After oral administration of stable isotope-labeled parent drug to rats and GC/MS analysis of plasma samples, two metabolites were identified: D3017, which is the primary alcohol, and 2,6-DMA, formed by amide bond hydrolysis of either D2624 or D3017. In urine, three metabolites of D2624 were identified: namely D3017,2,6-DMA, and D3270 (which is the carboxylic acid derivative of D3017). Based on plasma AUC analysis, D3017 and 2,6-DMA accounted for > 90% of the dose of D2624. After oral administration, D2624 was found to be well absorbed (93%), but underwent extensive first-pass metabolism in the rat, thus resulting in 5.3% bioavailability. Rat and human liver microsomal preparations were capable of metabolizing D2624 to D3017 and 2,6-DMA. The formation of D3017 was NADPH-dependent, whereas 2,6-DMA formation was NADPH-independent and probably was catalyzed by amidase(s) enzymes. In a single-dose (25-225 mg) human volunteer study, the parent drug (D2624) was not detected in plasma at any dose, whereas 2,6-DMA was detected only at the two highest doses (150 and 225 mg). D3017 was detected after all doses of parent drug, with approximate dose proportionality in AUC and a half-life of 1.3-2.2 hr. The metabolic behavior observed in humans suggests there is a marked species difference in the oxidative and hydrolytic pathways of D2624.

Aniline Compounds↗

Maximum likelihood estimation of the kappa coefficient from models of matched binary responses.

We present an estimate of the kappa-coefficient of agreement between two methods of rating based on matched pairs of binary responses and show that the estimate depends on the common intraclass correlation coefficient between the pairs. Via Monte Carlo simulation, we investigate power of the test of significance on kappa, and the large sample bias and variance of its maximum likelihood estimator.

Analysis of Variance↗

Atypical antagonism of D1-receptor-mediated vasodilator response in the perfused kidney by SCH23390.

Vasodilator responses to dopexamine, fenoldopam and dopamine, which are known to have agonist activity at D1-dopamine receptors, were examined in the rat isolated perfused kidney preparation. Perfusion pressure was raised by perfusing with the thromboxane TxA2 analogue, U46619, and vasodilator responses were observed as dose-related falls in perfusion pressure. Propranolol (10(-6) M) and prazosin (10(-6) M) were present throughout to eliminate beta 2 and alpha 1-adrenoceptor-mediated responses, respectively. The vasodilator responses were antagonized by SCH23390 (10(-9) M), indicating that they were mediated via D1-receptors. The displacements of the dose-response curves for fenoldopam, dopexamine and dopamine were, however, non-parallel with significant depression of the maxima to 30.2, 37.9 and 34.3%, respectively. In the presence of SCH23390 (10(-8) M) and prazosin (10(-6) M), dopexamine, isoprenaline and noradrenaline produced dose-related renal vasodilation. This was antagonized by propranolol indicating a role for beta-adrenoceptors. In the case of dopexamine, the maximum response was depressed in the presence of propranolol. The reason for the atypical blockade of vasodilator responses by SCH23390 was investigated. One possibility was the appearance of transient vasoconstrictor responses at higher doses of fenoldopam, dopexamine and dopamine, usually preceding the vasodilatation. The possibility was therefore considered that the vasoconstriction may have opposed the usual vasodilation at high doses and thus limited the size of the maximum vasodilation in the presence of SCH23390. The vasoconstriction by fenoldopam was not antagonized by S-sulpiride, the D2-receptor antagonist but was blocked by mianserin and therefore attributed to 5-HT2 receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Assessment of intestinal permeability changes induced by nonsteroidal anti-inflammatory drugs in the rat.

Intestinal permeability was investigated as an alternative to intestinal ulceration for measuring nonsteroidal anti-inflammatory drug (NSAID) gut damage in the rat and developed as a method for routine measurement. NSAID dose-response curves produced using the two indices of damage showed that intestinal permeability is as sensitive and reproducible as ulceration, although changes could not be detected before visible ulceration occurred. Lactulose, [51Cr]-EDTA and [14C]-carboxyinulin were compared as possible in vivo markers of rat intestinal permeability. Measurement of [51Cr]-EDTA permeation was found to be the most sensitive and reproducible method. Dose-response curves produced by measuring [51Cr]-EDTA permeation were used to compare the potency of the two NSAIDs piroxicam and (S+) ibuprofen; piroxicam was found to be 10 times more potent in increasing intestinal permeability than (S+)-ibuprofen. These studies show that intestinal permeability measurement is a useful alternative to other methods of assessing NSAID adverse effect and is easily and rapidly performed.

Animals↗

Regional drug delivery II: relationship between drug targeting index and pharmacokinetic parameters for three non-steroidal anti-inflammatory drugs using the rat air pouch model of inflammation.

PURPOSE: To quantify the advantage gained by direct administration to a target site for two non-steroidal anti-inflammatory drugs (NSAIDs) piroxicam and diclofenac in the rat air pouch model of inflammation. To derive a model relating drug targeting index (DTI) to the pharmacokinetic parameters of the target and systemic sites, and to compare predictions with observations. METHODS: DTI was calculated based on area under the concentration time curve at target (pouch) and systemic site (venous blood) following administration into and sampling from both sites. A model was derived relating DTI to systemic clearance, target permeability, plasma protein binding and fraction of the targeted dose that is systemically available. RESULTS: Both NSAIDs exhibited linear pharmacokinetics over the dose ranges studies. They differed primarily in total body clearance which was approximately 16 fold greater for diclofenac (213 ml hr-1 per 250 g) than piroxicam (13 ml hr-1 per 250 g). Observed DTIs (11, 114 and 276 for piroxicam, S[+]ibuprofen [studied previously] and diclofenac) were ranked in order of total body clearance but were approximately 7.5 fold lower than predicted (101, 700 and 2214 respectively). CONCLUSIONS: The discrepancy was explained by the influx of the plasma binding protein, albumin, into the target site due to increased vascular permeability associated with the inflammatory response. The originally derived equation for DTI, which assumed only unbound drug diffuses across the target site, was modified to take into account the simultaneous flux of bound drug.

Animals↗

Regional drug delivery I: permeability characteristics of the rat 6-day-old air pouch model of inflammation.

PURPOSE: To determine the permeability characteristics of the rat air pouch model of inflammation using permeability extremes within which the NSAIDs S[+] ibuprofen, piroxicam and diclofenac could be evaluated. METHODS: Permeability was calculated using concentration data obtained following intrapouch and intravenous administration of [3H]-water, [14C]-urea, [14C]-inulin and [125I]-albumin and compared to similar data obtained for the three NSAIDs. RESULTS: Similar permeability values (5-6.5 ml hr-1) were obtained for the three NSAIDS which fell between the permeability extremes of the molecular weight markers [3H]-water (9.7 ml hr-1), [14C]-urea (6.8 ml hr-1), [14C]-inulin (1.0 ml hr-1) and [125I]-albumin (0.6 ml hr-1). Coadministration of equipotent anti-inflammatory doses of the NSAIDs did not affect local blood flow to the air pouch (as assessed by urea kinetics) but did reduced vascular permeability (as assessed by albumin flux into the pouch). CONCLUSIONS: Comparison of the NSAIDs with the permeabilities of the molecular weight markers indicates that a perfusion rate limitation probably exists. Systemic absorption is complete over the first two hours following intrapouch administration of the NSAIDs, therefore albumin flux into the pouch is insufficient to materially affect the permeability of the NSAIDs. However, subsequently (post 5hr) albumin concentration in the pouch rises sufficiently to lower the effective flux of the NSAIDs.

Animals↗

Renal vasodilatation by dopexamine and fenoldopam due to alpha 1-adrenoceptor blockade.

1. The renal vascular responses of the rat isolated perfused kidney to the dopamine D1-receptor agonists, dopexamine and fenoldopam, were examined. 2. Both kidneys were perfused in situ at constant flow rate (11 ml min-1) with Krebs-bicarbonate solution at 37 degrees C. The perfusion pressure was monitored and to enable vasodilator responses to be measured, the resting perfusion pressure was raised by infusing noradrenaline (6 x 10(-9) M). 3. Dose-related vasodilator responses to bolus doses of dopexamine and fenoldopam were obtained. However, these were not antagonized by the D1-receptor antagonist, SCH 23390, indicating that D1-receptors were not involved. 4. Bolus doses of the alpha 1-adrenoceptor antagonist, prazosin, caused similar dose-related vasodilator responses indicating the possibility that alpha 1-adrenoceptor blocking properties of dopexamine and fenoldopam were responsible for the vasodilatation. 5. alpha-Adrenoceptor blockade by dopexamine and fenoldopam was confirmed by the parallel displacement of dose-response curves for the vasopressor responses to noradrenaline. pA2 values were determined by Schild analysis for dopexamine, fenoldopam and prazosin antagonism of noradrenaline in the presence of neuronal (cocaine, 10(-5) M) and extraneuronal uptake blockade (metanephrine, 10(-5) M). The values were 6.23, 6.02 and 8.91, respectively. Schild plot slopes of unity were obtained for dopexamine and fenoldopam indicating competitive antagonism. A slope of greater than unity for prazosin may be explained by the lack of equilibrium conditions associated with bolus doses of noradrenaline, the responses of which are affected more by the high affinity antagonist, prazosin, than the two lower affinity antagonists. 6. This study has demonstrated that renal vasodilator responses to the D,-receptor agonists, dopexamine and fenoldopam, are due to a brief antagonism of the alpha-adrenoceptor-mediated vasoconstriction induced by noradrenaline. This presumably masks any direct D1-receptor-mediated vasodilatation.

Adrenergic alpha-1 Receptor Antagonists↗

Pharmacodynamic comparison of regional drug delivery for non-steroidal anti-inflammatory drugs, using the rat air-pouch model of inflammation.

The inhibition of prostaglandin E2 (PGE2) synthesis by S-(+)-ibuprofen and piroxicam have been assessed following intravenous and regional (intrapouch) drug delivery using the rat air-pouch model of inflammation. Anti-inflammatory response was defined as the decrease in the area under the exudate PGE2 concentration-time curve between 3 and 10 h, following regional administration of the irritant carrageenan. Dose-response studies indicated that bolus regional administration of S-(+)-ibuprofen increased potency 30-fold compared with systemic administration and could be further improved 10-fold by regional infusion, whereas regional administration of piroxicam showed no therapeutic advantage. Examination of the concentration-response using AUC revealed that for a given response, average pouch concentrations for S-(+)-ibuprofen during the PGE2 inflammatory response (3 to 10 h) was similar, irrespective of route or mode of administration. In contrast, an advantage following systemic rather than regional administration was revealed for piroxicam, based on plasma concentration-response data, indicating a major systemic anti-inflammatory component for piroxicam but not for S-(+)-ibuprofen. These observations stress the need to take account of both pharmacodynamics and pharmacokinetics when considering the potential advantage of regional administration.

Animals↗

Genetic parameters for common health disorders of Holstein cows.

Observations on 7416 Canadian Holstein cows were examined to estimate genetic parameters for the most common diseases of dairy cows. Mastitis, ovarian cyst, ketosis, milk fever, abomasal displacement, and culling that is due to reproductive failure or leg problems were analyzed as binomial traits, assuming an underlying threshold model that included fixed and random effects. Sire and residual components of variance were estimated by REML to provide heritability estimates from paternal half-sibs. A multiple-trait mixed model was also used to estimate genetic and environmental correlations between production and disease traits. Heritabilities of disease traits were relatively low and ranged from 0 to .15, except for displaced abomasum (h2 = .28). Evidence of genetic antagonism existed between incidence of mastitis and milk production. Incidence of milk fever was genetically associated with cows of lower genetic potential for production. Genetic associations between displaced abomasum and production traits were small, and estimates of genetic correlations between ovarian cyst and milk production were inconsistent across lactations. Ketosis was antagonistically associated genetically with production of milk and fat but was favorably associated with production of protein. The long-term cumulative effect of genetic selection against diseases might be useful to diminish their incidence.

Abomasum↗