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Biomedical subjects

G L Carroll

Publications and source records attributed to G L Carroll.

At least 19 recordsLinked to original sources

Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration.

OBJECTIVE: To evaluate disposition of butorphanol after i.v. and i.m. administration, effects on physiologic variables, and analgesic efficacy after i.m. administration in llamas. DESIGN: Nonrandomized crossover study. ANIMALS: 6 healthy adult male llamas. PROCEDURE: Butorphanol (0.1 mg/kg [0.045 mg/lb] of body weight) was administered i.m. first and i.v. 1 month later. Blood samples were collected intermittently for 24 hours after administration. Plasma butorphanol versus time curves were subjected to pharmacokinetic analysis. Two months later, butorphanol (0.1 mg/kg) was administered i.m., and physiologic variables and analgesia were assessed. RESULTS: Extrapolated peak plasma concentrations after i.v. and i.m. administration were 94.8 +/- 53.1 and 34.3 +/- 11.6 ng/ml, respectively. Volume of distribution at steady state after i.v. administration was 0.822 +/- 0.329 L/kg per minute and systemic clearance was 0.050 +/- 0.014 L/kg per minute. Slope of the elimination phase was significantly different, and elimination half-life was significantly shorter after i.v. (15.9 +/- 9.1 minutes) versus i.m. (66.8 +/- 13.5 minutes) administration. Bioavailability was 110 +/- 49% after i.m. administration. Heart rate decreased and rectal temperature increased. Somatic analgesia was increased for various periods. Two llamas became transiently sedated, and 2 became transiently excited after butorphanol administration. CONCLUSIONS AND CLINICAL RELEVANCE: Although i.v. administration of butorphanol results in a short half-life that may limit its analgesic usefulness, the elimination half-life of butorphanol administered i.m. is likely to be clinically useful. The relationship among plasma butorphanol concentration, time, and analgesia differed with the somatic analgesia model; clinically useful analgesia may occur at lower plasma concentrations than those reported here.

Analgesics, Opioid↗

On the regiospecificity of vanadium bromoperoxidase.

Vanadium haloperoxidase enzymes catalyze the oxidation of halide ions by hydrogen peroxide, producing an oxidized intermediate, which can halogenate an organic substrate or react with a second equivalent of hydrogen peroxide to produce dioxygen. Haloperoxidases are thought to be involved in the biogenesis of halogenated natural products isolated from marine organisms, including indoles and terpenes, of which many are selectively oxidized or halogenated. Little has been shown concerning the ability of the marine haloperoxidases to catalyze regioselective reactions. Here we report the regiospecific bromoperoxidative oxidation of 1,3-di-tert-butylindole by V-BrPO from the marine algae Ascophyllum nodosum and Corallina officinalis. Both enzymes catalyze the regiospecific oxidation of 1,3-di-tert-butylindole in a reaction requiring both H(2)O(2) and Br(-) as substrates, but which produce the unbrominated 1,3-di-tert-butyl-2-indolinone product exclusively, in near quantitative yield (i.e. one H(2)O(2) consumed per product). By contrast, reactions with the controlled addition of aqueous bromine solution (HOBr = Br(2) = Br(3)(-)) produce three monobromo and one dibromo-2-indolinone products, all of which differ from the V-BrPO-catalyzed product. Further, reactivities of 1,3-di-tert-butyl-2-indolinone with both aqueous bromine and V-BrPO differ significantly and shed light onto the possible nature of the oxidizing intermediate. This is the first example of a regiospecific bromination by a vanadium haloperoxidase and further extends their usefulness as catalysts.

Binding, Competitive↗

Evaluation of transdermal fentanyl patches for analgesia in cats undergoing onychectomy.

OBJECTIVE: To evaluate efficacy and safety of using transdermal fentanyl patches (TFP) for analgesia in cats undergoing onychectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 45 client-owned cats weighing > or = 2.7 kg (5.9 lb) undergoing onychectomy, onychectomy and ovariohysterectomy, or onychectomy and castration. PROCEDURE: Cats were randomly assigned to be treated with a TFP (25 micrograms/h) or butorphanol; TFP were applied a minimum of 4 hours before surgery (approx 8 hours prior to extubation). Rectal temperature, heart rate, respiratory rate, force applied by the forelimbs, and serum fentanyl concentration were measured, and temperament, recovery, degree of sedation, severity of pain, severity of lameness, and appetite were scored before and periodically for up to 40 hours after surgery. RESULTS: Cats treated with a TFP had better recovery scores at 2 of 4 evaluation times, lower sedation scores at 2 of 8 evaluation times, and lower pain scores at 6 of 8 evaluation times, compared with cats treated with butorphanol. Use of a pressure-sensitive mat to evaluate force applied by the forelimbs did not reveal any differences between groups but did reveal a significant difference between preoperative and postoperative values. Mean +/- SD serum fentanyl concentrations were 1.56 +/- 1.08, 4.85 +/- 2.38, 4.87 +/- 1.56, and 4.35 +/- 2.97 ng/ml approximately 8, 24, 32, and 48 hours, respectively, after TFP placement. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of a TFP (25 micrograms/h) for postoperative analgesia in cats undergoing onychectomy with or without surgical sterilization is safe and effective.

Administration, Cutaneous↗

Analgesics and pain.

There has been a substantial increase in the use of analgesics for pain management in the last 10 years. Traditionally, veterinarians have not been trained in the identification of or monitoring of patients that are in pain, even though an evaluation of pain is inherent in assessing improvement in many medical and surgical diseases. Until recently, the physiology and pharmacology of opioids, NSAIDs, local anesthetics, and alpha 2 agonists were taught, but the therapeutic role of these drugs was generally believed to be related to restraint, anesthesia, or control of inflammation rather than to pain management.

Analgesics, Opioid↗

Pharmacokinetics of fentanyl after intravenous and transdermal administration in goats.

OBJECTIVE: To evaluate disposition of fentanyl in goats after IV and transdermal administration. ANIMALS: 8 healthy 2-year-old goats weighing 31.8 to 53.6 kg (mean+/-SD, 40.4+/-7.5 kg). PROCEDURE: Each goat was given 2 treatments consisting of fentanyl administered IV (2.5 microg/kg of body weight) and via a transdermal patch (50 microg/h). There was a 2-month interval between treatments. Blood samples were collected at specified times and analyzed in duplicate to determine plasma fentanyl concentrations. Pharmacokinetic values were calculated, using a computerized modeling program. RESULTS: Administration of fentanyl was tolerated by all goats. Intravenous administration of fentanyl resulted in a transitory increase in rectal temperature that was not clinically important. Terminal elimination half-life after IV administration was 1.20+/-0.78 h, volume of distribution at steady state was 1.51+/-0.39 L/kg, and systemic clearance was 2.09+/-0.62 L/kg/h. Transdermal administration of fentanyl resulted in variable plasma concentrations, with peak plasma concentrations ranging from 1.12 to 16.69 ng/ml (mean+/-SD, 6.99+/-6.03 ng/ml) and time to peak concentration ranging from 8 to 18 hours (mean+/-SD, 13+/-4.5 hours). After removal of the transdermal patch, mean+/-SD terminal elimination half-life was 5.34+/-5.34 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fentanyl (2.5 microg/kg) in goats results in a relatively short half-life that will limit its use for management of pain. Transdermal administration of fentanyl (50 microg/h) in goats results in variable plasma concentrations that may exceed those anticipated on the basis of a theoretical delivery rate, but stable plasma concentrations of fentanyl may not be achieved.

Administration, Cutaneous↗

Evaluation of analgesia provided by postoperative administration of butorphanol to cats undergoing onychectomy.

OBJECTIVE: To evaluate adequacy of analgesia provided by postoperative administration of butorphanol to cats undergoing onychectomy. DESIGN: Randomized controlled trial. ANIMALS: 63 cats undergoing elective onychectomy. PROCEDURE: Cats were randomly assigned to a treatment (n = 42) or control group (21). Cats in the treatment group were given butorphanol parenterally immediately and 4 hours after surgery and orally for 2 days after surgery. Rectal temperature, heart rate, and respiratory rate were recorded and scores were assigned for temperament, recovery, sedation, analgesia, and lameness for the first 24 hours after surgery. Owners provided scores for appetite, personality, and lameness the first and second days after discharge from the hospital. RESULTS: Heart rate, respiratory rate, rectal temperature, and temperament and sedation scores were not significantly different between groups at any evaluation time. Recovery scores were significantly better for butorphanol-treated than for control-group cats 10 minutes after extubation. Analgesia scores were significantly better for butorphanol-treated than for control-group cats between 5 and 24 hours after surgery. Fewer butorphanol-treated than control-group cats were lame at the time of discharge from the hospital. The first day after discharge, owners reported that percentages of butorphanol-treated cats that ate normally, acted normally, and had only mild or no lameness were significantly higher than percentages of control-group cats that did. Significant differences between groups were not detected the second day after discharge. CLINICAL IMPLICATIONS: Results suggest that for cats undergoing onychectomy, administration of butorphanol the day of surgery and the first full day after surgery provides effective analgesia and improves recovery, appetite, and gait.

Analgesia↗

Maintenance of anaesthesia with sevoflurane and oxygen in mechanically-ventilated horses subjected to exploratory laparotomy treated with intra- and post operative anaesthetic adjuncts.

Eight healthy horses premedicated with xylazine and induced with ketamine were used to evaluate sevoflurane in oxygen for maintenance of anaesthesia during elective exploratory laparotomy. After orotracheal intubation, horses were hoisted, placed in dorsal recumbency on a padded surgery table, and received sevoflurane in oxygen for maintenance of anaesthesia. The horses were allowed to breathe spontaneously until instrumented; then, they were mechanically ventilated to maintain the PaCO2 between 35 and 45 mmHg. Systolic (SAP), diastolic (DAP), and mean (MAP) arterial blood pressures, heart rate (HR), ECG, respiratory rate, an estimation of the saturation of haemoglobin with oxygen in peripheral arterial blood (S(p)O2), nasal temperature, end-tidal CO2(ET(CO2)), end-tidal sevoflurane (ET(SEVO)), and vaporiser concentration were recorded every 5 min post induction; arterial blood samples were obtained soon after induction, at 30 min after induction, and every hour thereafter until surgery was completed. Recovery data including times from the sevoflurane vaporiser being turned off to first movement, to sternal recumbency, and to standing, number of attempts to stand, and recovery score (between 1 = safe, smooth and 6 = stormy, major injury to horse) were collected. Analysis of variance was performed using physiological data collected over 195 min of anaesthesia, the longest time period during which all 8 horses were instrumented. Time effects (P<0.05) for HR, SAP, DAP, MAP, and nasal temperature were identified. Heart rate peaked at 45 min and declined over the course of the procedure. Arterial blood pressure generally decreased over time. Body temperature decreased over time. From 15 to 195 min mean ET(SEVO)concentration ranged from 2.0 to 3.3%, while mean vaporiser settings ranged from 3.7 to 5.5%. Three horses received intra-operative ketamine; all horses received dobutamine infusions; and 2 horses received intra-operative calcium-dextrose. Total anaesthesia time was 222-316 min (mean+/-s.d.269+/-31 min). Time from turning the sevoflurane vaporiser off to first movement was mean +/-s.d.18+/-15 min; to sternal recumbency was 54+/-22 min; to standing was 65+/-27 min; and to returning the horse to the stall in the ward was 78+/-24 min. Six horses stood on the first attempt; 2 horses stood on the second attempt. The median recovery score was one (1-3). In conclusion, sevoflurane provided a stable, easily controllable anaesthetic plane during prolonged exploratory laparotomies; horses experienced smooth, safe recoveries after maintenance of anaesthesia with sevoflurane following routine anaesthetic induction and post operative xyalzine administration.

Adjuvants, Anesthesia↗

Anesthetic effects of tiletamine-zolazepam, alone or in combination with butorphanol, in goats.

OBJECTIVE: To evaluate anesthetic effects of tiletamine-zolazepam (TZ), alone or in combination with butorphanol, in goats undergoing laparotomy for embryo collection. DESIGN: Randomized clinical trial with crossover design. ANIMALS: 9 adult female goats. PROCEDURE: Goats were anesthetized twice: once with TZ (5.5 mg/kg [2.5 mg/lb] of body weight, i.v.) and once with tiletamine-zolazepam and butorphanol (0.1 mg/kg [0.045 mg/lb], i.v.). Additional doses of TZ (0.5 to 1.0 mg/kg [0.23 to 0.45 mg/lb], i.v.] were administered as needed to maintain a surgical anesthetic plane. Time to sternal recumbency was recorded, and quality of induction was scored. Arterial pressures, heart rate, respiratory rate, and rectal temperature were recorded every 5 minutes; arterial blood samples were collected every 30 minutes. Oxygen was insufflated if estimated saturation of hemoglobin in peripheral arterial blood with oxygen was < 90%; intermittent positive-pressure ventilation was performed if goats became apneic. Muscle relaxation, quality of anesthesia, and eye signs were scored every 15 minutes during anesthesia. Anesthesia time was recorded, and quality of recovery and degree of postoperative analgesia were scored. Plasma cortiso concentration was measured before induction, immediately after extubation, and 2 hours after extubation. RESULTS: Induction was rapid and smooth. Five goats regurgitated, 3 required supplemental oxygen, and 1 required intermittent positive-pressure ventilation, but none of the goats became hypotensive. Muscle relaxation and quality of anesthesia were adequate. Goats recovered from anesthesia without complications. We did not detect any significant differences between anesthetic regimens for any of the variables measured, except bicarbonate concentration and base excess. CLINICAL IMPLICATIONS: TZ at a dose of 5.5 mg/kg was satisfactory for anesthetic induction in goats; additional doses can be given to extend anesthesia time, but addition of butorphanol at a dose of 0.1 mg/kg to this regimen does not seem to provide any measurable benefit. An oxygen source and a means of assisting ventilation should be available.

Analgesics, Opioid↗

Three methods of oxytocin-induced parturition and their effects of foals.

OBJECTIVE: To compare effects of 3 oxytocin-based induction techniques on fetal and neonatal foals. DESIGN: Prospective randomized controlled trial. ANIMALS: 16 pregnant mares. PROCEDURE: Parturition was induced in mares by use of 3 treatments: group 1, 75 U of oxytocin, IM; group 2, 15 U of oxytocin, IM, q 15 minutes, for a maximum of 75 U; group 3, 75 U of oxytocin in 1 L of 0.9% NaCl solution IV (1 U/min), for a maximum of 75 U. Blood gas values and indices of vitality were measured in foals, and variables describing parturition were measured in mares. RESULTS: Group-3 mares had a shorter interval from administration of oxytocin to rupture of the chorioallantois (OTCA) than group-2 mares. More foals were abnormal when the interval from oxytocin administration to delivery of the foal (OTDE) was > or = 60 minutes. Arterial blood gas values, measurements of vitality, and plasma cortisol concentrations did not differ among foals in various treatment groups. Increased interval for OTCA and OTDE resulted in higher neonatal PaCO2, and a longer interval for OTCA resulted in lower arterial pH. Time required for birth was shorter in mares with a dilated cervix. More abnormal foals than normal foals were delivered after premature placental separation or dystocia. Abnormal foals took longer to stand and suckle than normal foals. Interval from delivery to suckling was positively correlated with OTCA, OTDE, and PaCO2. CLINICAL IMPLICATIONS: Method of oxytocin-induced parturition did not impact neonatal outcome. Interval from induction until parturition, degree of cervical dilatation, and intrapartum complications influenced induction success.

Animals↗

General anesthetic techniques in ruminants.

Sedation, anesthesia, protection of the airway during general anesthesia, and control of pain in the perioperative period are important considerations in the management of sheep, goats, and cattle. Though ruminants are classically considered farm animals and are often intended for the production of food and fiber, these species are used extensively in research and teaching and they are increasingly important as companion animals. Whatever their use may be, anesthetic and analgesic drugs and techniques should be used to ensure minimal stress and discomfort during the perioperative period.

Analgesia↗

Age-related changes in deformability of human erythrocytes.

The present study was designed to further the characterization of age-related changes in the deformability of human erythrocytes. The top (approximately young) and bottom (approximately old) 10% fractions of density-separated red cells from ten normal donors were subjected to graded levels of shear stress in a rheoscope. Measurements were made of steady-state elongation (cells tank treading in a state of dynamic equilibrium) and the time course of shape recovery following abrupt cessation of shear. In parallel with the rheologic experiments, several physical and chemical properties were assayed to determine correlates of mechanical properties. These included mean cell volume, mean corpuscular hemoglobin concentration, type A1 hemoglobin, glucosylation of membrane proteins, and membrane phospholipid and protein concentration. The microrheologic observations revealed that only about 90% of the old cells retained their capacity to tank tread. However, the tank-treading cells elongated less than their younger counterparts at corresponding levels of shear stress, thus demonstrating a reduced level of deformability. Further analysis of the data indicates that increases in membrane viscosity and elastic modulus along with a significant loss in excess surface area contribute to the limitation of the ability of the older cells to change shape.

Adult↗

Microrheologic investigation of erythrocyte deformability in diabetes mellitus.

This study was undertaken to determine whether diabetes alters the viscoelastic properties of erythrocytes. The oldest and youngest 10% fractions of circulating red cells were separated by centrifugation of freshly drawn blood obtained from ten diabetics with disease of one to 20 years' duration and from an equal number of age- and sex-matched control subjects. Cells from each fraction were suspended in phosphate-buffered saline, and their rheologic behavior was examined in a rheoscope. The elongation of cells, the percentage of cells that tank-treaded in response to shear stress, tank-treading frequency, and the rate of recovery of cell shape upon cessation of shear stress were determined in the oldest and youngest 10% of cells for diabetics as well as for controls. All four parameters were virtually identical for diabetics and controls. Additional aliquots of cells were taken for assessment of nonenzymatic glucosylation of hemoglobin and cell membrane protein. The absence of any measurable difference in rheologic behavior of cells from diabetic and control subjects, despite substantial differences in nonenzymatic glucosylation of hemoglobin and cell membrane proteins, suggests that the magnitude of glucosylation observed in these cellular constituents does not alter the viscoelastic properties of the cells. The implication of these observations is that microvascular complications of diabetes are not attributable to altered deformability of red cells.

Adult↗

Plasmodium falciparum maturation abolishes physiologic red cell deformability.

Normal red cells deform markedly as they pass through the spleen and the peripheral capillaries. In these studies, the effects of Plasmodium falciparum infection and maturation on the deformability of parasitized red cells exposed to fluid shear stress in vitro were examined by means of a rheoscope. Red cells containing the early (ring) erythrocytic stage of the parasite have impaired deformability at physiologic shear stresses, and recover their normal shape more slowly. Red cells containing more mature parasites (trophozoites or schizonts) exhibit no deformation under the same conditions. These results provide a mechanism to explain the ability of the spleen to remove parasitized red cells from the circulation of both immune and nonimmune hosts.

Animals↗

Detomidine-propofol anesthesia for abdominal surgery in horses.

OBJECTIVE: To evaluate propofol for induction and maintenance of anesthesia, after detomidine premedication, in horses undergoing abdominal surgery for creation of an experimental intestinal adhesion model. STUDY DESIGN: Prospective study. ANIMALS: Twelve horses (424 +/- 81 kg) from 1 to 20 years of age (5 females, 7 males). METHODS: Horses were premedicated with detomidine (0.015 mg/kg i.v.) 20 to 25 minutes before induction, and a propofol bolus (2 mg/kg i.v.) was administered for induction. Propofol infusion (0.2 mg/kg/min i.v.) was used to maintain anesthesia. The infusion rate was adjusted to maintain an acceptable anesthetic plane as determined by muscle relaxation, occular signs, response to surgery, and cardiopulmonary responses. Oxygen (15 L/min) was insufflated through an endotracheal tube as necessary to maintain the SpO2 greater than 90%. Systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressures, heart rate (HR), electrocardiogram (ECG), respiratory rate (RR), SpO2 (via pulse oximetry), and nasal temperature were recorded at 15 minute intervals, before premedication and after induction of anesthesia. Arterial blood gas samples were collected at the same times. Objective data are reported as mean (+/-SD); subjective data are reported as medians (range). RESULTS: Propofol (2.0 mg/kg i.v.) induced anesthesia (mean bolus time, 85 sec) within 24 sec (+/-22 sec) after the bolus was completed. Induction was good in 10 horses; 2 horses showed signs of excitement and these two inductions were not smooth. Propofol infusion (0.18 mg/kg/min +/- 0.04) was used to maintain anesthesia for 61 +/- 19 minutes with the horses in dorsal recumbency. Mean SAP, DAP, and MAP increased significantly over time from 131 to 148, 89 to 101, and 105 to 121 mm Hg, respectively. Mean HR varied over time from 43 to 45 beats/min, whereas mean RR increased significantly over anesthesia time from 4 to 6 breaths/min. Mean arterial pH decreased from a baseline of 7.41 +/- 0.07 to 7.30 +/- 0.05 at 15 minutes of anesthesia, then increased towards baseline values. Mean PaCO2 values increased during anesthesia, ranging from 47 to 61 mm Hg whereas PaO2 values decreased from baseline (97 +/- 20 mm Hg), ranging from 42 to 57 mm Hg. Muscle relaxation was good and no horses moved during surgery: Recovery was good in 9 horses and acceptable in 3; mean recovery time was 67 +/- 29 minutes with 2.4 +/- 2.4 attempts necessary for the horses to stand. CONCLUSIONS: Detomidine-propofol anesthesia in horses in dorsal recumbency was associated with little cardiovascular depression, but hypoxemia and respiratory depression occurred and some excitement was seen on induction. CLINICAL RELEVANCE: Detomidine-propofol anesthesia is not recommended for surgical procedures in horses if dorsal recumbency is necessary and supplemental oxygen is not available (eg, field anesthesia).

Abdomen↗

Comparison of three methods for relief of pain after ear canal ablation in dogs.

This study compared three methods of pain relief in dogs that had total ear canal ablation with lateral bulla osteotomy. The hypothesis was that systemic opioids with preoperative local nerve blocks would provide superior pain relief. Thirty-one dogs with chronic otitis externa were included in the study. Dogs were randomly assigned to one of three protocols: systemic opioids alone (10 dogs, group 1), systemic opioids with bupivacaine splash block (11 dogs, group 2), and systemic opioids with preoperative local bupivacaine nerve blocks (10 dogs, group 3). Twenty-one dogs had bilateral ear ablation and 10 had unilateral ablation. Pain was assessed preoperatively, at extubation, 2 hours postextubation, and 1 day postoperatively by a single observer blinded to the analgesic protocol used. Pain scores were not significantly different within or between groups, nor did unilateral versus bilateral ablation have a significant effect on the score. Mean scores were less than 3 (scale 1 to 5) for all groups at all observation times. Rough recoveries were noted in 30% of group 1 dogs, 0% of group 2, and 20% of group 3 dogs. Ninety-four percent of dogs were moderately to heavily sedated at extubation. Sixty percent of group 3 dogs remained moderately to heavily sedated 2 hours postextubation. Rectal temperature, pulse rate, respiratory rate, and postoperative change in serum cortisol levels were not significantly different between groups. Postoperative increase in blood glucose was significantly higher in groups 1 and 3 compared with preoperative levels. Twenty-three percent of the dogs required additional analgesia or tranquilization after surgery, as determined by the anesthetist; 1 dog in group 1, 2 in group 2, and 4 in group 3. Each of the three analgesic protocols provided similar pain relief in dogs undergoing total ear canal ablation.

Analgesics, Opioid↗