A pilot study: sodium urate synovitis as an acute model of inflammatory response using objective and subjective criteria to evaluate arthritic pain in cats.

Sodium urate (SU) synovitis was evaluated as a model for feline arthritic pain using a placebo- and positive-controlled (meloxicam) randomized blinded controlled single crossover design. Monosodium urate crystals [20 mg (1 mL) rod-shaped] were injected into alternate stifles of trained anesthetized cats (n = 3) with a 28 day washout. During the first trial phase, two cats received meloxicam (0.1 mg/kg, PO), a nonsteroidal anti-inflammatory drug (NSAID), for three days before and on the day of SU injection; the third cat received placebo. Treatments and stifles were switched for the second trial. Total force, contact pressure and area of the fore and hind limbs were measured using a pressure mat one day and 0.5 h before, and 2, 4, 6, 8, 10, 24, and 30 h post-SU injection. Skin temperature, joint circumference, analgesia, lameness, and visual analogue scale (VAS) pain scores, were measured at the same times. Comparisons were made for each time and for areas under the curve (AUC) using original and change from baseline; P < 0.05 was significant. Significant differences in force mat data and subjective data were found for the hind limb data (total force and total contact pressure at 6, 10, and 30 h; analgesia and VAS for pain at 4 h; lameness at 10, 24, and 30 h) and for AUC(0)-->(24h) and AUC(0)-->(30 h) (total force, total contact pressure, and mean lameness score) and for differences from BL AUC(0)-->(10h) (total contact area) and AUC(0)-->(24h) (total contact area and mean lameness score) and AUC(0)-->(30 h) (total force, total contact area, and mean lameness). No cats required rescue analgesia. Injection of 1 mL of monosodium urate into the stifle of a cat causes moderate transitory pain and was suitable for assessing analgesic efficacy of an NSAID with a pressure mat and subjective criteria.

Emprego do propofol, isofluorano e morfina para a anestesia geral de longa duraçäo em bezerros / Use of propofol, isoflurane and morphine for prolonged general anesthesia in calves

Foram estudadas características da bioquímica do sangue, da pressäo arterial e da freqüência de pulso de 12 bezerros mantidos sob anestesia por 13 horas, utilizando-se propofol para a induçäo e isofluorano para manutençäo, associados à administraçäo de morfina intra-tecal. Os valores de freqüência de pulso, pressäo arterial e glicemia apresentaram pequenas variaçöes e se mantiveram próximos dos valores de referência para bezerros anestesiados. Ao longo do período de anestesia houve aumento significativo, mas discreto, do hematócrito, hemoglobina, pCO2, CO2 total, bicarbonato e potássio. O pH do sangue, pO2, Na+ e Ca++ apresentaram reduçöes significativas. Este protocolo anestésico foi seguro para a manutençäo de bezerros anestesiados por período prolongado.

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.

A multisite case report on the clinical use of sevoflurane in dogs.

The purpose of this report was to evaluate the clinical safety and efficacy of sevoflurane as an inhalant anesthetic in dogs. Subjective and objective data from 196 clinical cases utilizing sevoflurane as the maintenance anesthetic was collected at three sites. After preanesthetic evaluation, the attending anesthesiologist assigned the dogs to one of the following six anesthetic protocols: protocol 1, oxymorphone premedication and thiopental induction; protocol 2, oxymorphone/acetylpromazine premedication and thiopental induction; protocol 3, xylazine/butorphanol premedication and thiopental induction; protocol 4, opioid premedication and propofol induction; protocol 5, optional premedication and mask induction with sevoflurane in oxygen; and protocol 6, optional premedication and optional induction. The average quality of induction, maintenance, and recovery was good to excellent in all protocols. The three most common side effects during maintenance and recovery were hypotension, tachypnea, and apnea. Sevoflurane produces anesthesia in dogs comparable to the other inhalation anesthetics currently used (i.e., halothane and isoflurane) for diagnostic or therapeutic procedures.

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.

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.

Inter- and intramolecular reductive coupling reactions: an approach to the phorbol skeleton.

[reaction: see text] An expeditious convergent route to the ABC-tricyclic core of the phorbol esters is described. The chemistry capitalizes upon both inter- and intramolecular reductive coupling processes promoted electrochemically and via the use of samarium diiodide.

Atom transfer reactions of TMM diyls directed toward the synthesis of rudmollin.

Intramolecular hydrogen atom transfer to a trimethylenemethane (TMM) diradical has been explored as a route to the antileukemial agent, rudmollin (1).

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.

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).

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.

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.

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.

Detomidine-butorphanol-propofol for carotid artery translocation and castration or ovariectomy in goats.

OBJECTIVE: To determine the safety and efficacy of propofol, after detomidine-butorphanol premedication, for induction and anesthetic maintenance for carotid artery translocation and castration or ovariectomy in goats. STUDY DESIGN: Case series. ANIMALS: Nine 4-month-old Spanish goats (17.1 +/- 2.6 kg) were used to evaluate propofol anesthesia for carotid artery translocation and castration or ovariectomy. METHODS: Goats were premedicated with detomidine (10 micrograms/kg intramuscularly [i.m.]) and butorphanol (0.1 mg/kg i.m.) and induced with an initial bolus of propofol (3 to 4 mg/kg intravenously [i.v.]). If necessary for intubation, additional propofol was given in 5-mg (i.v.) increments. Propofol infusion (0.3 mg/kg/min i.v.) was used to maintain anesthesia, and oxygen was insufflated (5 L/min). The infusion rate was adjusted to maintain an acceptable anesthetic plane as determined by movement, muscle relaxation, ocular signs, response to surgery, and cardiopulmonary responses. Systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures, heart rate (HR), ECG, respiratory rate (RR), SpO2, and rectal temperature (T) were recorded every 5 minutes postinduction; arterial blood gas samples were collected every 15 minutes. Normally distributed data are represented as mean +/- SD; other data are medians (range). RESULTS: Propofol (4.3 +/- 0.9 mg/kg/min i.v.) produced smooth, rapid (15.2 +/- 6 sec) sternal recumbency. Propofol infusion (0.52 +/- 0.11 mg/kg/min i.v.) maintained anesthesia. Mean anesthesia time was 83 +/- 15 minutes. Muscle relaxation was good; eye signs indicated surgical anesthesia; two goats moved before surgery began; one goat moved twice during laparotomy. Means are reported over the course of the data collection period. Means during the anesthesia for pHa (arterial PH), PaCO2, PaO2, HCO3-, and BE (base excess) ranged from 7.233 +/- 0.067 to 7.319 +/- 0.026, 54.1 +/- 4.6 to 65.3 +/- 12.0 mm Hg, 133.1 +/- 45.4 to 183.8 +/- 75.1 mm Hg, 26.9 +/- 2.6 to 28.2 +/- 2.1 mEq/L, and -0.8 +/- 2.9 to 1.4 +/- 2.2 mEq/L. Means over time for MAP were 53 +/- 12 to 85 +/- 21 mm Hg. Mean HR varied over time from 81 +/- 6 to 91 +/- 11 beats/minute; mean RR, from 9 +/- 8 to 15 +/- 5 breaths/minute; SpO2 from 97 +/- 3% to 98 +/- 3%; mean T, from 36.0 +/- 0.6 degrees C to 39.1 +/- 0.7 degrees C. Over time, SpO2 and SaO2 did not change significantly; HR, RR, T, and PaCO2 decreased significantly; SAP, DAP, MAP, pHa, PaO2, and BE increased significantly. HCO3- concentrations increased significantly, peaking at 45 minutes. Recoveries were smooth and rapid; the time from the end of propofol infusion to extubation was 7.3 +/- 3 minutes, to sternal was 9.2 +/- 5 minutes, and to standing was 17.7 +/- 4 minutes. Median number of attempts to stand was two (range of one to four). Postoperative pain was mild to moderate. CONCLUSIONS: Detomidine-butorphanol-propofol provided good anesthesia for carotid artery translocation and neutering in goats. CLINICAL RELEVANCE: Detomidine-butorphanol-propofol anesthesia with oxygen insufflation may be safely used for surgical intervention in healthy goats.