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Biomedical subjects

R C Wilson

Publications and source records attributed to R C Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1989

A pilot study of three potential vaccines for leprosy in Bombay.

Three vaccines, BCG Glaxo alone (vaccine A), BCG Glaxo plus 10(7) killed Mycobacterium vaccae (vaccine B), and BCG Glaxo plus 10(7) killed M. leprae (vaccine C), were given to groups of selected children. The effects of these vaccines on subsequent quadruple skin testing 1-3 years after vaccination were compared. All three vaccines equally and significantly (p less than 0.00001) increased positivity to tuberculin, but only vaccine B was found to significantly enhance development of skin-test positivity to leprosin A (p less than 0.002). The data support the evidence previously obtained in rural Iran that the combination of BCG with killed M. vaccae is likely to be a better vaccine for leprosy than is BCG alone.

Adolescent↗
PubMed1989

Bioavailability of gentamicin in dogs after intramuscular or subcutaneous injections.

Healthy adult mixed-breed dogs, assigned to 2 groups of 6 dogs each, were given 3 mg of gentamicin sulfate/kg of body weight on 3 injection days 7 days apart. Group 1 was given gentamicin by rapid IV injection, by injection into the belly of the longissimus muscle at the first lumbar vertebrae (IM site 1), and by injection in the belly of the biceps femoris muscle (IM site 2). Group 2 was given gentamicin by rapid IV injection, by SC injection into the space over the cranial angle of the scapula on the midline (SC site 1), and by SC injection just caudal to the crest of the ilium (SC site 2). Pharmacokinetic values (mean +/- SD) from 12 dogs given gentamicin IV were 54.4 +/- 15.4 minutes for the effective half life, 2.29 +/- 0.48 ml/kg/min for clearance, and 172 +/- 25.4 ml/kg for volume of distribution at steady state. Bioavailability (93.92 to 96.65%) and peak plasma gentamicin concentration (9.43 to 10.89 micrograms/ml) were independent of injection site, but time to peak concentration when gentamicin was given at SC site 2 (43.33 minutes) was significantly (P less than 0.05) longer than that when gentamicin was given at IM site 1 (27.50 minutes). Absorption half-life was shorter after injections were given at both IM sites (8.9 and 9.8 minutes) than after injection was given at SC site 2 (18 minutes).

Animals↗
PubMed1988

Comparison of neuromuscular blockade in upper facial and hypothenar muscles.

Facial and hand muscles are used frequently for monitoring neuromuscular blockade. Therefore, we compared changes in electrically evoked muscle potential magnitude in upper facial and hypothenar muscles after fixed doses of neuromuscular blockers (succinylcholine, 750 micrograms/kg; pancuronium, 70 micrograms/kg; vecuronium, 50 micrograms/kg; and atracurium, 300 micrograms/kg). Face-hand comparisons were made in both anesthetized (nitrous oxide/narcotic, n = 51) and comatose (closed-head injuries, n = 5) patients. In 24 anesthetized patients, complete blockade of the hypothenar muscles prevented quantitative comparison. In the remaining 27 patients, the relaxant effect (as determined by the percentage change from prerelaxant baseline muscle potentials) was significantly smaller (P less than 0.0001) in the upper facial muscles (65 +/- 24% versus 92 +/- 8%, mean +/- SD). All four evoked muscle responses to train-of-four stimulation were detectable in upper facial muscles of the 19 patients receiving non-depolarizing neuromuscular blocking drugs; this pattern was seen in hand muscles of only 7 patients (P less than 0.001). The neuromuscular blockade in both the hand (49 +/- 54%) and the upper facial area (68 +/- 28%, P greater than 0.05) of comatose patients was smaller and more variable than that seen during anesthesia. These results illustrate the value of quantitative monitoring of neuromuscular function, especially during highly variable and unpredictable drug-induced blockade in the comatose state. We conclude that during narcotic-based anesthesia the upper facial and hand muscles are differentially sensitive to commonly used neuromuscular blockers.

Anesthesia, General↗
PubMed1988

Pharmacokinetics of gentamicin in cats given Escherichia coli endotoxin.

Nineteen cats were given 3 mg of gentamicin sulfate/kg of body weight by rapid IV, SC, or IM injection for baseline values. Serum concentration of gentamicin vs time data were analyzed using a noncompartmental model based on statistical moment theory. One week later, each cat was given 0.5 microgram of Escherichia coli endotoxin/kg, IV. After cats had an increase in rectal temperature of at least 1 C, 3 mg of gentamicin/kg was administered by the same route used the previous week. Serum concentration of gentamicin vs time data were analyzed, and pharmacokinetic values were compared with base-line values. For IV studies, the half-life (t1/2) of gentamicin and the mean residence time were significantly different (P less than 0.05) compared with base line, whereas the total body clearance and apparent volume of distribution at steady state were not. The harmonic mean +/- pseudo SD for the t1/2 of gentamicin after IV administration was 76.8 +/- 12.6 minutes for base line and was 65.2 +/- 12.2 minutes in the same cats given endotoxin. The t1/2 of gentamicin after SC administration was 74.6 +/- 6.2 minutes for base line and was 65.2 +/- 13.6 minutes in the same cats given endotoxin. After IM administration, the t1/2 of gentamicin was 60.3 +/- 10 minutes for base line and was 59.7 +/- 13.6 minutes in the same cats given endotoxin. After IV administration of gentamicin, the arithmetic mean +/- SD for the mean residence time was 102.4 +/- 16.1 minutes for base line vs 79.2 +/- 18.4 minutes in the same cats given endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Pathologic changes and tissue gentamicin concentrations after intravenous gentamicin administration in clinically normal and endotoxemic cats.

Hematologic and serum biochemical values, tissue gentamicin concentrations, and renal pathologic changes were determined in clinically normal and endotoxemic cats given 3 mg of gentamicin/kg of body weight, IV. Endotoxemia was induced by IV administration of 0.5 microgram of Escherichia coli endotoxin/kg of body weight. In experiment 1, 6 cats were given endotoxin. After rectal temperature increased at least 1 degree C, cats were given gentamicin. Blood samples were collected before and at 1 and 3 hours after administration of gentamicin. With the exception of severe leukopenia, other hematologic changes or changes in serum biochemical values were not observed. In experiment 2, 24 cats were allotted to 4 groups and were given gentamicin, endotoxin, gentamicin plus endotoxin, or neither substance. Three hours later, cats were euthanatized, and tissue and body fluid specimens were obtained and were assayed for gentamicin concentration. Kidney specimens were examined microscopically. Endotoxemic cats had more gentamicin in the renal medulla than did control cats, but none of the cats had detectable renal lesions. The possible nephrotoxic synergism between gentamicin and severe endotoxemia and the lack of major differences in gentamicin concentration in extrarenal tissues indicated that the dosage of gentamicin in endotoxemic cats does not have to exceed the dosage recommended for clinically normal cats. A single dose of gentamicin administered IV did not cause renal damage in mildly endotoxemic cats, but nephrotoxicity ascribed to multiple doses of gentamicin in more severely endotoxemic cats needs to be evaluated.

Animals↗
PubMed1988

Pharmacokinetics of doxycycline in dogs.

Six adult dogs were given doxycycline hyclate at a dosage of 5 mg/kg of body weight intravenously so that pharmacokinetic parameters could be evaluated. Serum doxycycline concentrations were determined over a 48 h period using a modified agar well bioassay. Compartmental pharmacokinetic evaluation of the serum concentration time data indicated that doxycycline has a half-life of 10.36 h, a body clearance of 1.68 +/- 0.44 mL/min/kg, and a volume of distribution at steady state of 1.468 +/- 0.237 L/kg. Doxycycline pharmacokinetics are favorable for therapeutic use in the dog.

Animals↗
PubMed1988

Pharmacokinetics of gentamicin after intravenous, intramuscular, and subcutaneous administration in cats.

Six adult mixed breed cats were given 5 mg of gentamicin sulfate/kg of body weight by rapid IV, IM, or SC injection. The serum concentration vs time data were analyzed, using a noncompartmental model based on statistical moment theory. The mean +/- SD for the effective half-life after IV administration was 1.25 +/- 0.30 hours. Mean residence time was 1.80 +/- 0.43 hours. The apparent volume of distribution at steady state was 0.14 +/- 0.02 L/kg. Total body clearance was 1.38 +/- 0.35 ml/min/kg. Bioavailability was 67.8% after IM and 76.2% after SC administration. A recommended dosage of 3 mg of gentamicin/kg every 8 hours was calculated; this dosage would induce an average steady state serum gentamicin concentration of 4 micrograms/ml. The SC route of administration was preferred because of rapid absorption, good bioavailability, and ease of administration.

Animals↗
PubMed1988

Pharmacokinetics of amikacin in cats.

Six mixed-breed adult cats were given 5 mg of amikacin sulfate/kg of body weight by rapid IV, IM, and SC routes of administration. The serum concentration-vs-time data were analyzed, using a noncompartmental model. The harmonic mean +/- pseudo-SD of the effective half-life of amikacin was 78.8 +/- 19.3 minutes after IV administration, 118.7 +/- 14.4 minutes after IM administration, and 117.7 +/- 12.8 minutes after SC administration. The arithmetic mean +/- SD of mean residence time was 118.3 +/- 21.7 minutes, 173.4 +/- 19.9 minutes, and 171.7 +/- 19.1 minutes after IV, IM, and SC drug administration, respectively. The mean apparent volume of distribution at steady state was 0.17 +/- 0.02 L/kg, and the mean total body clearance was 1.46 +/- 0.26 ml/min/kg. Mean bioavailability was 95 +/- 20% after IM administration and 123 +/- 33% after SC drug administration. A recommended dosage of 10 mg/kg, q 8 h can be expected to provide a therapeutic serum concentration of amikacin with a mean steady-state concentration of 14 micrograms/ml. The SC route of administration is preferred, because of rapid absorption, good bioavailability, and ease of administration.

Amikacin↗
PubMed1988

Comparative pharmacokinetics of yohimbine in steers, horses and dogs.

In steers, horses and dogs, the comparative pharmacokinetics of yohimbine were determined using model-independent analysis. The intravenous dose of yohimbine was 0.25 mg/kg of body weight in steers, 0.075 or 0.15 mg/kg in horses, and 0.4 mg/kg in dogs. The mean residence time (+/- SD) of yohimbine was 86.7 +/- 46.2 min in steers, 106.2 +/- 72.1 to 118.7 +/- 35.0 min in horses, and 163.6 +/- 49.7 min in dogs. The mean apparent volume of distribution of yohimbine at steady state was 4.9 +/- 1.4 L/kg for steers, 2.7 +/- 1.0 to 4.6 +/- 1.9 L/kg for horses, and 4.5 +/- 1.8 L/kg for dogs. The total body clearance of yohimbine was 69.6 +/- 35.1 mL/min/kg for steers, 34.0 +/- 19.4 to 39.6 +/- 16.6 mL/min/kg for horses, and 29.6 +/- 14.7 mL/min/kg for dogs. Between-species comparisons indicated that the mean area under the serum concentration versus time curve was significantly greater (P less than 0.05) in dogs than in horses. There were no significant differences (P greater than 0.05) between the means for the apparent volume of distribution, clearance, mean residence time, terminal rate constant, and area under the curve between horses given the two doses of yohimbine. The harmonic mean effective half-life (+/- pseudo standard deviation) of yohimbine was 46.7 +/- 24.4 min in steers, 52.8 +/- 27.8 to 76.1 +/- 23.1 min in horses, and 104.1 +/- 32.1 min in dogs. The data may explain why steers, horses, and dogs given certain sedatives and anesthetics do not relapse when aroused by an intravenous injection of yohimbine hydrochloride.

Animals↗
PubMed1988

Pharmacokinetics of tobramycin in cats.

Tobramycin was administered to cats and its serum concentration vs time data were analyzed by use of a noncompartmental model. In the first experiment, 5 mg of tobramycin/kg of body weight was administered IV, IM, and then SC to 6 cats, 3 weeks apart. After IV administration, the mean +/- SD total body clearance of tobramycin was 2.21 +/- 0.59 ml/min/kg, and the apparent volume of distribution at steady state was 0.19 +/- 0.03 L/kg. The mean residence time was 90.5 +/- 16.2 minutes, with a harmonic mean serum half-life of 68.9 +/- 9.7 minutes. Blood urea nitrogen and serum creatinine concentrations were increased 3 weeks after the IV injection and also 3 weeks after the IM injection, which suggested possible renal damage. Moreover, large area under the curve values developed after IM and SC administrations, resulting in bioavailabilities of 159.5% and 189.9%, respectively, with no change in elimination rate. These results suggested a change in distribution, possibly caused by saturation of renal binding sites by residual tobramycin from the previous injection of 5 mg/kg. In experiment 2, 6 other cats were given 3 mg of tobramycin/kg by the same routes as before, but using a crossover design. Bioavailability after IM and SC administrations was 102.5% and 99.2%, respectively, indicating complete absorption of tobramycin. The BUN concentration increased in 3 cats, and serum creatinine concentration increased in 1 of these 3 cats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Unexpected responses of the hypothalamic gonadotropin-releasing hormone "pulse generator" to physiological estradiol inputs in the absence of the ovary.

In the rhesus monkey (Macaca mulatta), the frequency of pulsatile gonadotropic hormone release is relatively constant in the face of widely varying levels of estradiol (E2) in the peripheral circulation--e.g., in the course of the follicular phase of the menstrual cycle and after ovariectomy. This suggests that modulation of the hypothalamic gonadotropin-releasing hormone (GnRH) "pulse generator" by this steroid is not of major physiological importance. Herein is described the unexpected inhibition or total blockade of the electrical activity of this pulse generator in ovariectomized monkeys by physiological levels of exogenous E2. This inhibition began 2-4.5 hr after the initiation of E2 infusion and was noted 1 to 3 weeks after subcutaneous implantation of E2-containing capsules. Pulse generator activity was also arrested during the initiation and subsequent development of estrogen-induced surges of luteinizing hormone. We propose that this inhibition of hypothalamic GnRH pulse generator activity by E2 in ovariectomized monkeys reflects the absence of an ovarian factor that normally protects this neuronal system from the inhibitory action of estrogen during the menstrual cycle.

Action Potentials↗
PubMed1986

Localization of the binding site for protein S4 on 16 S ribosomal RNA by chemical and enzymatic probing and primer extension.

We have examined the effect of binding ribosomal protein S4 to 16 S rRNA on the susceptibility of the RNA to a variety of chemical and enzymatic probes. We have used dimethyl sulfate to probe unpaired adenines (at N-1) and cytosines (at N-3), kethoxal to probe unpaired guanines (at N-1 and N-2) and cobra venom (V1) ribonuclease as a probe of base-paired regions of 16 S rRNA. Sites of attack by the probes were identified by primer extension using synthetic oligodeoxynucleotides. Comparison of probing results for naked and S4-bound rRNA shows: Protein S4 protects a relatively compact region of the 5' domain of 16 S rRNA from chemical and enzymatic attack. This region is bounded by nucleotides 27 to 47 and 394 to 556, and has a secondary structure characterized by the junction of five helical elements. Phylogenetically conserved irregular features (bulged nucleotides, internal loops and flanking unpaired nucleotides) and helical phosphodiester bonds of four of the helices are specifically protected in the S4-RNA complex. We conclude that this is the major, and possibly sole region of contact between 16 S rRNA and S4. Many of the S4-dependent changes mimic those observed on assembly of 16 S rRNA into 30 S ribosomal subunits. Binding of S4 causes enhanced chemical reactivity coupled with protection from V1 nuclease outside the S4 junction region in the 530, 720 and 1140 loops. We interpret these results as indicative of loss of structure, and suggest that S4 binding causes disruption of adventitious pairing in these regions, possibly by stabilizing the geometry of the RNA such that these interactions are prevented from forming.

Autoradiography↗
PubMed1986

Electronic spreadsheet program for estimating two-compartment intravenous pharmacokinetic parameters by least squares linear regression analysis.

A microcomputer program using an electronic spreadsheet program was developed to calculate pharmacokinetic values of thiacetarsamide sodium, a drug used to kill the adult heartworm (Dirofilaria immitis) parasite of the dog. A least squares, semilogarithmic regression analysis was done on data using a two compartment intravenous model. The data entered includes the time after injection and the drug concentration at that time. A graph of the points can be viewed or plotted, with the time on the x-axis, and the natural log of the drug concentration on the y-axis. The program was developed on a Televideo (512 kbytes) microcomputer. The spreadsheet used was Lotus 123 with the pharmacokinetics program occupying 16 kbytes of memory (720 cells) out of the 400 kbytes available with Lotus.

Animals↗
PubMed1986

On the short-loop feedback regulation of the hypothalamic luteinizing hormone releasing hormone 'pulse generator' in the rhesus monkey.

The characteristic electrophysiological manifestations of LHRH 'pulse generator' activity were unaffected by prolonged elevations in plasma LH concentrations achieved by the administration of a long-acting LHRH agonist. These findings do not lend support to the existence of a 'short-loop feedback' inhibition of LHRH 'pulse generator' activity by LH.

Animals↗
PubMed1986

The effect of morphine on the electrophysiological activity of the hypothalamic luteinizing hormone-releasing hormone pulse generator in the rhesus monkey.

In ovariectomized rhesus monkeys, the electrophysiological manifestation of luteinizing hormone-releasing hormone (LHRH) pulse generator activity was arrested by morphine and reinitiated by naloxone. These responses were noted within 1 and 2 min, respectively, after the intravenous injection of the drugs. Naloxone given alone had no effect. These results support the view that opioids modulate pulsatile gonadotropin release by an action on the hypothalamic LHRH pulse generator.

Animals↗