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R C Wilson

Publications and source records attributed to R C Wilson.

At least 73 records · Page 4Linked to original sources

Application of an enzyme-multiplied immunoassay technique for determination of caffeine elimination kinetics as a test of liver function in clinically normal dogs.

A commercially available automated enzyme-multiplied immunoassay technique (EMIT) was used to determine serum caffeine concentration after oral and IV administrations of caffeine at dosage of 5 mg/kg of body weight to 12 clinically normal dogs. Dogs were allotted to 2 groups of 6 dogs each; 1 group initially received caffeine orally and the other received caffeine IV. After 72 hours, caffeine administration was repeated in all dogs in the alternate manner. Serum samples were obtained at multiple intervals over 24 hours to determine distribution and elimination kinetics. Analysis of the drug concentration-time data indicated IV elimination half-life (t1/2) of 6.39 +/- 1.87 hours, volume of distribution at steady state of 685.3 +/- 132.2 ml/kg, total body clearance of 1.31 +/- 0.38 ml/min/kg, absorption t1/2 of 1.02 +/- 0.68 hour, oral elimination t1/2 of 6.53 +/- 2.72 hours, lag time after oral administration of 0.0614 +/- 0.0661 hour, highest measured concentration of 5.29 +/- 1.17 micrograms/ml, time to peak concentration of 2.74 +/- 1.30 hours, and bioavailability of 99.4 +/- 19.4%. Data from 6 dogs best fit a 1-compartment open model and those from 6 other dogs best fit a 2-compartment open model. On the basis of data from the 6 dogs that best fit a 2-compartment model, t1/2 of distribution was 0.58 +/- 0.72 hour. Data for oral administration best fit a single absorption phase and a single elimination phase. The increased availability and simplicity of the EMIT offers an opportunity to study the application of caffeine elimination for clinical evaluation of dogs with liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effect of residence at altitude on the perception of breathlessness on return to sea level in normal subjects.

1. The effect of residence at altitude on the perception of breathlessness after return to sea level was examined in normal subjects. Breathlessness (Borg scale), minute ventilation, respiratory frequency, tidal volume, 'oxygen pulse' (oxygen consumption/heart rate) and the ventilatory equivalent for oxygen (minute ventilation/oxygen consumption) were measured at exercise (cycle-ergometer) during 5 months of training before 4 weeks at 4000 m and during the 6 month period after return to sea level. 2. There was no change in the subjects' pattern of breathing (respiratory frequency and tidal volume) or 'oxygen pulse' after the period at altitude (P = 0.0001). The ventilatory equivalent for oxygen was increased at all work rates after the period at altitude (P = 0.02). This ratio was slightly lower after 6 weeks and had returned to normal by 6 months (P = 0.4). 3. During training there was no change in breathlessness score (P = 0.6). On return to sea level, breathlessness score relative to ventilation was reduced (P = 0.0001). This was maintained for at least 6 weeks, but not as long as 6 months. 4. This study has demonstrated that, in normal subjects, the otherwise stable and reproducible relationship between breathlessness and ventilation may be disrupted for several weeks by factors other than lung disease. 5. The mechanism responsible for this is not clear, but the observations are consistent with the hypothesis that prior experience of breathlessness may condition subsequent estimates of breathlessness.

Adult↗

Treatment of subclinical mastitis.

Topics addressed in this article include applied pharmacology of the bovine mammary gland, principles of antibiotic sensitivity testing, mechanisms of antimicrobial resistance, causes of treatment failures, diagnostic considerations, and therapy of specific subclinical mastitis syndromes. Recent research concerning systemic therapy of subclinical mastitis is highlighted and critically reviewed. Limitations of antibiotic sensitivity testing are discussed. The lack of proven, efficacious therapy for many subclinical mastitis syndromes is emphasized.

Animals↗

Acyclovir (Zovirax) pharmacokinetics in Quaker parakeets, Myiopsitta monachus.

The pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) single-dose administration of acyclovir were determined in Quaker parakeets. After i.v. injection at a dose of 20 mg/kg of acyclovir, elimination half-life was estimated at 0.65 h, volume of distribution at steady state was 627.65 ml/kg, and clearance was 11.22 ml/kg/min. The estimated pharmacokinetic values after i.m. injection at a dose of 40 mg/kg of acyclovir were an elimination half-life of 0.71 h and a bioavailability of 90.1%. The peak plasma acyclovir concentration occurred at 15 min when the drug was administered i.m. Plasma concentrations of acyclovir were undetectable 4-6 h after i.v. administration and 6-8 h after i.m. administration. Oral (capsules) and intravenous (sodium salt) formulations of acyclovir were given by gavage at 80 mg/kg. Peak concentrations with the sodium salt formulation were lower and developed more slowly than with the capsules. In studies designed to detect excessive drug accumulation or adverse side effects, acyclovir was administered i.m. at 40 mg/kg every 8 h for 7 days. Plasma concentrations were determined 15 min after (peak) and just prior to drug administration (trough). In another study acyclovir was gavaged at a dose of 80 mg/kg every 8 h for 4 days. Acyclovir plasma concentrations were determined just prior to and 2 h after drug administration. In both experiments, the birds maintained normal appetite and weight and did not exhibit excessive drug accumulation. Acyclovir plasma concentrations ranging from 2.07 +/- 1.09 micrograms/ml to 3.93 +/- 1.13 micrograms/ml were maintained for 4 days when acyclovir was administered in the feed and water (sole source of food and water).(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

Intramammary administration of gentamicin as treatment for experimentally induced Escherichia coli mastitis in cows.

In 8 Holstein cows, 50 colony-forming units (CFU) of Escherichia coli was administered into 1 mammary gland. Infections were established in all inoculated glands. In 4 of the 8 cows, 500 mg of gentamicin sulfate was administered by intramammary infusion 14 hours after inoculation; the other 4 cows were untreated controls. Infusions of gentamicin also were given after each of the 3 successive milkings after the initial infusion, so that a total dose of 2 g of gentamicin was given to each of the treated cows. During the 33-hour treatment period and for the first milking after the last infusion of gentamicin, the treated cows had a mean gentamicin concentration of greater than or equal to 31.0 micrograms/ml in milk samples that were collected from inoculated quarters immediately before each milking. Concentrations of 0.34 and 0.69 micrograms of gentamicin/ml were detected in milk from 2 cows at 8 days after inoculation with E coli. Mean serum concentrations of gentamicin were greater than or equal to 0.37 micrograms/ml throughout the treatment period and the first 12 hours after the last infusion, with a mean peak concentration of 0.96 micrograms/ml at 24.4 hours. The range of peak concentration of gentamicin detected in urine from all treated cows was 42 to 74.4 micrograms/ml. Peak concentration of E coli in milk in the treated cows (6.08 +/- 1.02 log10 CFU/ml) did not significantly (P greater than 0.05) differ from that of the control cows (5.26 +/- 1.00 log10 CFU/ml). Similarly, mean duration of infection in the treated cows (54 hours) did not differ significantly from that of the control cows (48 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Differentiation between the intensity of breathlessness and the distress it evokes in normal subjects during exercise.

1. This study was designed to examine whether normal subjects could differentiate between the 'intensity' of their breathlessness and the amount of 'distress' it evoked, by specific wording of the instructions. 2. A preliminary study showed no significant difference between 'distress' score during exercise measured on two separate occasions (P = 0.3). 3. Ten subjects each performed two identical incremental cycle-ergometer exercise tests on separate occasions during which they were asked to quantify either 'intensity' or 'distress' by using modified Borg scales. 4. In all subjects there was a significant correlation (P less than 0.001) between 'intensity' and minute ventilation. In eight subjects there was a significant correlation (P less than 0.05) between 'distress' and minute ventilation. One subject displayed no significant correlation and one registered no distress. 5. Mean 'intensity' was greater than the mean 'distress' (P = 0.0001). The slope of 'intensity'/minute ventilation was greater than the slope of 'distress'/minute ventilation (P = 0.0001). 6. Within individuals there was a significant correlation between 'intensity' and 'distress' (P less than 0.05). There was a wide scatter in the slope of this relationship between subjects and maximum 'intensity' and 'distress' did not correlate. 7. Different elements of the breathlessness sensation could be identified and selectively measured depending on the wording of the instructions given to the subject. 8. There was a wide intersubject variation in the magnitude of both breathlessness 'intensity' and 'distress' estimates, but the differences between subjects in these two components of the sensation did not appear to follow a common pattern.

Adult↗

Long-term reproducibility of Borg scale estimates of breathlessness during exercise.

1. The intensity of breathlessness in normal subjects during exercise was measured on seven occasions over a 40-week study period to assess the long-term repeatability of Borg scale estimates of breathlessness. 2. In all subjects there was a significant correlation (P = 0.0001) between breathlessness and minute ventilation. Minute ventilation measured at each work rate did not differ between the seven exercise tests (P greater than 0.05). 3. There was no significant difference between the mean Borg scores (measured with respect to a given level of ventilation) in 5 of the 7 test weeks (P greater than 0.05). The slope of the relationship Borg score/minute ventilation did not differ between the seven exercise tests (P greater than 0.05). 4. Breathlessness estimation was highly reproducible both after 1 week and after 40 weeks of the study (both P greater than 0.05). 5. The duration without testing between consecutive tests did not affect reproducibility: the mean Borg score was as equally reproducible after an interval of 22 weeks without testing as after an interval of 1 week (P greater than 0.05). 6. The Borg scale provides a reliable technique for studying the sensation of breathlessness over extended time periods.

Adult↗

Pharmacokinetics of gentamicin after intravenous and subcutaneous injection in obese cats.

Six adult domestic shorthair obese cats were given 3-mg/kg gentamicin sulfate by rapid i.v. and by s.c. injection in a cross-over design. The plasma concentration-time data were analyzed using statistical moment theory with no assumption of a specific compartmental model. Means +/- SD for the half-life, which was calculated from the terminal slope of the log concentration-time curve, were 1.37 +/- 0.24 and 1.24 +/- 0.22 h following i.v. and s.c. injection, respectively. The apparent volume of distribution at steady state was 118.55 +/- 19.83 ml/kg, and total body clearance was 1.07 +/- 0.25 ml/kg/min. Bioavailability was 83.58 +/- 14.83% after s.c. administration. The calculated s.c. dose in obese cats to produce an average steady-state concentration of 4 micrograms/ml is 2.5 mg/kg every 8 h compared to 3 mg/kg in normal-weight cats.

Animals↗

Radiotelemetric monitoring of hypothalamic gonadotropin-releasing hormone pulse generator activity throughout the menstrual cycle of the rhesus monkey.

Continuous monitoring of the electrophysiological manifestations of GnRH pulse generator activity was achieved by radiotelemetry throughout the menstrual cycles of unrestrained rhesus monkeys. The characteristic increases in hypothalamic multiunit activity (MUA volleys) associated with each LH pulse measured in the peripheral circulation were of lower frequency during the luteal phase than in the follicular phase of the cycle. Multiunit activity volley frequency increased as functional luteolysis progressed and achieved maxima of approximately one volley per hour within the first few days of the follicular phase. Unexpectedly, a dramatic decline in pulse generator frequency was observed coincidentally with the initiation of the preovulatory LH surge. Evidence is presented to support the conclusion that this deceleration of pulse generator activity is the consequence of the preovulatory rise in plasma estrogen concentration. As reported in women, a significant reduction in GnRH pulse generator frequency was observed at night during the follicular phase, but not during the luteal phase, of the menstrual cycle.

Animals↗

Effect of diet on gentamicin-induced nephrotoxicosis in horses.

Gentamicin sulfate-induced nephrotoxicosis was compared in 2 groups of horses fed different rations. Four horses were fed only alfalfa hay, and 4 other horses were fed only whole oats. Seven days after initiation of the diet, all horses were given gentamicin IV (5 mg/kg of body weight) every 12 hours for 22 days. Urinary gamma-glutamyl-transferase to urinary creatinine (UGGT:UCr) ratio was calculated daily, and serum concentration of gentamicin was measured at 1 and 12 hours after drug administration. Results indicated that horses fed oats had greater renal tubular damage than did horses fed alfalfa. Mean UGGT:UCr for horses fed alfalfa was 47.1 +/- 18.8 and was 100.0 +/- 19.0 for horses fed oats (P = 0.007). The UGGT:UCr in horses fed oats was greater than 100 for a total of 54 days; horses fed alfalfa had UGGT:UCr greater than 100 for only 7 days. Two horses not given gentamicin were fed only oats and 2 were fed only alfalfa. These horses had mean UGGT:UCr of 17.6 +/- 2.2 and 30.5 +/- 3.0, respectively. Mean peak and trough concentrations of gentamicin were statistically different for horses fed oats and those fed alfalfa (peak 23.16 +/- 1.87 and 14.07 +/- 1.79 micrograms/ml, respectively [P = 0.0001], and trough, 1.81 +/- 0.69 and 0.71 +/- 0.70 micrograms/ml, respectively [P = 0.0270]). Mean half-lives of gentamicin (estimated from peak and trough concentrations) for horses fed alfalfa (2.58 +/- 0.26 hours) and horses fed oats (2.88 +/- 0.27 hours) were not significantly different. Horses fed only oats had greater degree of gentamicin-induced nephrotoxicosis than did those fed only alfalfa.

Animal Feed↗

Influence of prior ventilatory experience on the estimation of breathlessness during exercise.

1. The intensity of breathlessness was measured during exercise in nine normal subjects using a modified Borg scale to examine the effect of prior experience of breathlessness on subsequent estimates of breathlessness. 2. Each subject performed four exercise tests, each of which consisted of two identical runs of workload incrementation (run 1 and run 2). An inspiratory resistive load of 3.8 cmH2O s-1 l-1 was applied during the appropriate run of the exercise test to examine the effect of (a) prior experience of 'loaded' breathing on breathlessness estimation during 'unloaded' breathing, and (b) prior experience of 'unloaded' breathing on breathlessness estimation during 'loaded' breathing. Run 1 was the conditioning run: run 2 was the run in which the effect of conditioning was measured. 3. There was a good correlation between breathlessness and minute ventilation during both 'unloaded' breathing (median r = 0.93) and 'loaded' breathing (median r = 0.95). 4. The slope of the Borg score/minute ventilation relationship was greater during 'loaded' breathing than during 'unloaded' breathing (P less than 0.01). There was no difference in mean Borg score between 'unloaded' and 'loaded' breathing. 5. After a period of 'loaded' breathing during run 1, estimated breathlessness was significantly reduced during ensuing 'unloaded' breathing in run 2 (P less than 0.01) compared with the exercise test in which 'unloaded' breathing was experienced throughout both run 1 and run 2. 6. After a period of 'unloaded' breathing in run 1, estimated breathlessness was significantly increased during ensuing 'loaded' breathing in run 2 (P less than 0.01) compared with the exercise test in which the inspiratory load had already been experienced in run 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of ambient temperature on amikacin pharmacokinetics in gopher tortoises.

The pharmacokinetics of amikacin were compared in two groups of tortoises, one held at 20 degrees C and the other at 30 degrees C. The mean (+/- SD) residence time for amikacin in the 30 degrees C tortoises was 22.67 +/- 0.50 h; significantly (P less than 0.05) less than those held at 20 degrees C (41.83 +/- 3.23 h). There was no significant difference (P greater than 0.05) in the steady-state volume of distribution (Vd(ss] between the tortoises held at 30 degrees C (0.241 +/- 0.520 l/kg) and those held at 20 degrees C (0.221 +/- 0.019 l/kg). The clearance rate was faster (P less than 0.05) in the warmer tortoises (10.65 +/- 2.42 ml/min/kg at 30 degrees C compared to 5.27 +/- 0.152 ml/min/kg at 20 degrees C). These data indicate that while the volume of distribution was approximately the same, amikacin remained in the colder tortoises longer because of its slower elimination. The oxygen consumption and metabolism were measured and found to be lower in the colder tortoises, almost by the same 2:1 ratio as clearance time (Cl), mean residence time (MRT), and area under the curve (AUC). The data derived from this limited study indicated that an appropriate therapeutic dosage regimen for amikacin in gopher tortoises at 30 degrees C is 5 mg/kg given i.m. every 48 h.

Amikacin↗

Adverse effects of gentamicin in scarlet macaws and galahs.

The adverse effects of administration of gentamicin (5 mg/kg of body weight, IM, q 12 h) for 7 days were studied in healthy scarlet macaws (Ara macao) and galahs (Eolophus roseicapillus; cockatoos). Polydipsia and polyuria developed in each species, but were greater and persisted longer in the cockatoos. Peak water intake in the cockatoos more than quadrupled, and remained increased for 23 days after cessation of gentamicin administration. Plasma aspartate transaminase activity increased significantly (P less than 0.05) after treatment in the macaws, and plasma aspartate transaminase and lactate dehydrogenase activities increased in the cockatoos. Single IM administration of gentamicin (5 mg/kg) resulted in mean (+/- SEM) plasma concentration of 20.6 (+/- 1.85) micrograms/ml at 0.5 hour for either species of birds. There were no significant differences between mean plasma gentamicin concentrations for cockatoos and macaws at any time after drug administration, except at 12 hours, when values for cockatoos were significantly (P less than 0.05) greater than those for macaws. The elimination half-life for gentamicin after IM administration of 5 and 10 mg/kg was 1.17 and 1.07 hours, respectively, for macaws and 1.23 and 1.44 hours, respectively, for cockatoos. Correlation between drug disposition and adverse side effects could not be detected.

Animals↗

Complementation of in vitro-assembled spliceosomes.

We describe the development and application of a system of in vitro-assembled splicing complexes that can be used for the identification of protein splicing factors which become associated with the spliceosome at the end of the assembly process ("late" splicing components). A splicing reaction performed in the presence of polyvinyl alcohol is interrupted after 15 to 20 minutes, before the appearance of splicing intermediates and products in significant amounts. Following low-speed centrifugation, a pellet is obtained containing splicing complexes that can be solubilized with 0.6 M-KCl. These complexes can be rapidly complemented for splicing in the presence of ATP and Mg2+ with protein factors that are present in HeLa cell nuclear extracts or in chromatographic extract fractions. Biochemical features of the complementation reactions, and conditions for reversible uncoupling of the two splicing steps, are described and discussed. These conditions are used to generate fully assembled spliceosomes in which splicing of the pre-mRNA can occur in the presence of ATP and Mg2+, but in the absence of nuclear extract ("autonomous splicing").

Adenosine Triphosphate↗

A comparison of the visual analogue scale and modified Borg scale for the measurement of dyspnoea during exercise.

1. The intensity of breathlessness during exercise was measured in ten normal subjects using a visual analogue scale (VAS) and a Borg scale to compare the use of the scales and their repeatability, both within the duration of a period of exercise and between tests. For each scale, subjects performed two exercise tests separated by a period of 2-6 weeks. Each exercise test consisted of two cycles of progressively increasing and decreasing workload. 2. All subjects felt confidently able to use both scales to quantify their feelings of breathlessness exclusively of other sensation. Equal preference was expressed for use of a particular scale. 3. With both scales there was a large intersubject variation in the relationship between dyspnoea score and minute ventilation (VE) (P less than 0.01), and in the range of the scale used. 4. There was a good correlation between the VAS and Borg scores at each level of VE (r2 = 0.71), but the VAS score was used over a wider range than the Borg score. 5. The relationship between VE and the dyspnoea score measured by the two techniques was predominantly linear. The mean r2 for VAS score/VE was 0.68 (SD 0.19) and for Borg score/VE the mean r2 was 0.75 (SD 0.13). 6. The relationships VAS score/VE and Borg score/VE were unaffected by the direction in which the workload was varied (P greater than 0.05). 7. VE, measured at each work rate, did not differ between the two cycles (P greater than 0.05) or between the 2 days (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Autonomous splicing and complementation of in vivo-assembled spliceosomes.

We have used an in vivo system generating assayable amounts of a specific pre-mRNA to study the relationship between splicing and an operationally defined nuclear matrix preparation (NM). When NM is prepared by extraction of DNase I-treated nuclei with an approximately physiological concentration of KCl (0.1 M), a portion of NM-associated precursor can be spliced in vitro in the presence of ATP and Mg2+ and in the absence of splicing extract ("autonomous splicing"). We propose that the autonomous reaction, which does not exhibit a temporal lag and is half-complete in 5 min, occurs in fully assembled, matrix-bound ribonucleoprotein complexes (in vivo spliceosomes). Extraction of the NM with concentrations of KCl greater than 0.4 M eliminates autonomous splicing but leaves behind preassembled complexes that can be complemented for splicing with HeLa cell nuclear extract. The splicing complementing factor, representing one or more activities present in the nuclear extract and also in the cytoplasmic S100 fraction, is relatively heat resistant, devoid of an RNA component, and does not bind to DEAE-Sepharose in 0.1 M KCl. It exists in the nucleus in two forms; bound to autonomous spliceosomes and free in the nucleoplasm. Biochemical features of the complementation reaction, and conditions for reversible uncoupling of the two splicing steps are described and discussed.

Adenosine Triphosphate↗