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Biomedical subjects

D R Cook

Publications and source records attributed to D R Cook.

At least 73 records · Page 4Linked to original sources
PubMed1990

Efficacy of a killed gpX deleted pseudorabies virus vaccine.

Ten inactivated vaccines containing one of four adjuvants and varying concentrations of pseudorabies virus (PRV) antigens were compared in order to select a vaccine suitable for commercial production. A genetically engineered strain of PRV lacking the gene coding for glycoprotein X (gpX) was used in these vaccines. Vaccinated pigs were challenged intranasally with virulent PRV to determine the efficacy of vaccines. Vaccination of pigs with one dose of experimental vaccines adjuvanted with 50% Montanide ISA 50 or 20% Syntrogen induced a protective immunity at least equal to that induced by two commercially available killed PRV vaccines also evaluated. An experimental vaccine containing 20% Syntrogen was selected and further evaluated according to United States Department of Agriculture licensing requirements. None of the pigs vaccinated with this vaccine produced gpX antibodies detectable by the HerdChek: Anti-PRV-gpX assay. Therefore, this assay could differentiate PRV vaccine induced antibodies from antibodies induced by natural exposure when used in conjunction with this killed gpX deleted PRV vaccine.

Animals↗
PubMed1989

Mechanisms of hypertension during and after orthotopic liver transplantation in children.

The aim of this study was to assess the hormonal alterations that may mediate the systemic hypertension that develops in patients during the perioperative period of orthotopic liver transplantation. We studied nine pediatric patients without previous hypertension or renal disease during six time points, starting before transplantation and ending at 48 hours after surgery. Hypertension developed in all patients in association with central venous pressures less than 10 mm Hg. Free water clearance was negative in all nine patients. Vasopressin levels increased intraoperatively but fell as hypertension developed. Atrial natriuretic factor levels increased as systemic blood pressure rose. A high level of plasma renin activity was observed in four patients with renal insufficiency. In six patients, postoperative 24-hour urinary norepinephrine excretion was within the normal age-adjusted range. These findings suggest that the combination of cyclosporine, corticosteroids, and, in some patients, an elevated plasma renin activity prevents the kidney from responding to the acute volume and salt overload with an appropriate diuresis and natriuresis, thus leading to systemic hypertension. The treatment of hypertension after liver transplantation may include salt restriction, diuretics, and, in those patients with a low creatinine excretion index, angiotensin coverting enzyme inhibitors.

Adolescent↗
PubMed1989

Comparison of mivacurium and suxamethonium administered by bolus and infusion.

Mivacurium chloride is a new, short-acting nondepolarizing neuromuscular blocking agent presently undergoing clinical evaluation. The neuromuscular effects of mivacurium and suxamethonium given by bolus and infusion were compared in adult patients during nitrous oxide-oxygen-opioid anaesthesia. Neuromuscular block was monitored by recording the compound electromyogram of the adductor pollicis muscle resulting from supramaximal train-of-four stimuli applied to the ulnar nerve. Time to onset of complete block and recovery to T5 were significantly shorter for suxamethonium than for mivacurium (1.0 (0.1) v. 2.5 (0.3) min and 6.4 (0.7) v. 17.5 (1.8) min; mean (SEM]. Conditions for tracheal intubation were similar in the two groups although intubation was performed 0.75-1.3 min later following mivacurium. The infusion rate required to maintain neuromuscular block was 88.6 (10.4) micrograms kg-1 min-1 for suxamethonium and 7.8 (1.2) micrograms kg-1 min-1 for mivacurium. There was a significant negative correlation between recovery to T5 and infusion rate for mivacurium and for suxamethonium. It was equally easy to titrate the infusion rate to the desired degree of block in each group. The recovery index (T25-T75) after the infusion stopped was similar in patients who received mivacurium and those who received suxamethonium.

Adolescent↗
PubMed1989

An evaluation of three serological tests for antibody to Brucella suis in pigs.

The Rose Bengal Plate Agglutination test (RBT), the complement fixation text (CFT) and the tube agglutination test (TAT) were applied to serums from 345 feral and 80 domestic pigs sampled at slaughter. At least 2 of the 3 serological tests were applied to each serum. Tissues from all pigs were cultured for Brucella suis and the degree of culture effort was categorised from 1 to 4 in decreasing order. Fifty-eight feral and 35 domestic pigs were culture-positive. A greater proportion of culture-positive pigs was obtained for category 1 and 2 culture effort. Tissues yielding B. suis most often were mandibular, gastrohepatic and external iliac lymph nodes, spleen and various abdominal organs. Infection in domestic pigs was associated with exposure to feral pigs. The sensitivity (Se) in culture-positive pigs of the RBT (79.1%) was significantly greater than that of either the CFT (49.1%) or TAT (51.1%). The specificities (Sp) in culture-negative pigs were 81.2% for the RBT, 90.8% for the CFT and 81.0% for the TAT. A more realistic estimate of Sp for the RBT was considered to be 97.6%, based on serological results from 31,326 domestic pigs routinely tested for regulatory purposes. The RBT was clearly superior to the other 2 tests in this study. However, a more sensitive screening test would be preferable for use in a test and slaughter eradication program. The RBT would be a suitable confirmatory test.

Agglutination Tests↗
PubMed1989

Pharmacokinetics of alfentanil in newborn premature infants and older children.

Because developmental pharmacokinetics appear to be closely associated with anatomic and physiologic changes that occur with growth, we were interested in determining the disposition and elimination of alfentanil in premature infants and older children. The pharmacokinetic profile of alfentanil was determined in 6 premature infants requiring sedation for medical management or analgesia for stressful intensive-care procedures. These pharmacokinetic profiles were compared with pharmacokinetic profiles determined in 9 older infants and children undergoing operative procedures that required invasive monitoring. In both groups the plasma decay curves best fit a 2-compartment model. Compared with older children, premature infants demonstrated a significantly larger apparent volume of distribution (1.0 +/- 0.39 vs. 0.48 +/- 0.19 l/kg), a smaller clearance (2.2 +/- 2.4 vs. 5.6 +/- 2.4 ml/kg/min) and a markedly prolonged elimination half-life (525 +/- 305 vs. 60 +/- 11 min).

Age Factors↗
PubMed1989

Clinical pharmacology of mivacurium chloride (BW B1090U) in children during nitrous oxide-halothane and nitrous oxide-narcotic anesthesia.

We determined the dose-response relationships of mivacurium (BW B1090U) in children (2-10 years) during nitrous oxide-halothane anesthesia (0.8% end-tidal) and during nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relationships, for each anesthetic background four subgroups of nine patients received single bolus doses of 20-120 micrograms/kg mivacurium. The ED50 and ED95 (estimated from linear regression plots of log-dose vs. probit of effect) were 52 micrograms/kg and 89 micrograms/kg during halothane anesthesia and 62 micrograms/kg and 103 micrograms/kg during narcotic anesthesia. Nine additional patients in each anesthetic group received 250 micrograms/kg mivacurium. Three of the 18 patients given 250 micrograms/kg mivacurium developed cutaneous flushing; in one of these mean arterial pressure decreased 32% for less than 1 minute; no significant changes in heart rate occurred. With the increase in mivacurium dose from 120 micrograms/kg to 250 micrograms/kg the times to onset of 90% and maximum neuromuscular block decreased by 0.5 to 1 minute, and the times to recovery of neuromuscular transmission to 5% (T5) or 25% (T25) increased by 2-4 minutes. The recovery index (T25-75) in patients anesthetized with halothane was 4.3 +/- 1.5 minute (mean +/- SD); the time to complete recovery (T4:1 greater than or equal to 0.75) was 19.8 +/- 7.4 minutes.

Age Factors↗
PubMed1989

A method to increase recovery of fentanyl from urine.

Fentanyl, a highly lipophilic drug (pk(a) 7.7), is a common drug of abuse. The current standard techniques to detect fentanyl in urine have low recovery rates and poor sensitivity. We report a modified solvent extraction technique that can recover between 63 and 86% of the drug with a detection limit of 0.2 ng/10 ml of urine. In addition, we report the duration of urinary fentanyl excretion in 11 adolescent patients administered either low (less than 10 mg/kg) or high (20-40 mg/kg) doses of fentanyl as part of anesthesia. The mean duration of urinary fentanyl excretion was similar in the two groups, with duration ranging from 1 to 5 days, and urine fentanyl concentration ranging from 0.1 ng to 10.3 ng/10 ml of urine.

Adolescent↗
PubMed1989

Effects of cholestatic hepatic disease and chronic renal failure on alfentanil pharmacokinetics in children.

The role of the liver and the kidney in alfentanil metabolism has not been defined. The effects of cholestatic hepatic disease and chronic renal failure on the pharmacokinetics of alfentanil were evaluated in 9 children undergoing liver transplantation and 10 children undergoing kidney transplantation. These findings were compared with data from 10 children with normal hepatic and renal function undergoing other surgical procedures. There was no statistical difference among the 3 groups with respect to apparent volume of distribution, half-life, or clearance. In a subgroup of 3 patients undergoing liver transplantation alfentanil kinetics were determined both before and after the allograft was incorporated into the recipient's circulation. Though both volume of distribution and elimination half-life increased in the posttransplantation period, only the decrease in clearance was statistically significant. Thus, it appears that alfentanil may be a useful anesthetic agent in pediatric patients with cholestatic hepatic disease or chronic renal failure. The dose of alfentanil in these patients need not be altered except in the period immediately after liver transplantation.

Adolescent↗
PubMed1989

In vitro metabolism of mivacurium chloride (BW B1090U) and succinylcholine.

The in vitro rates of metabolism of mivacurium chloride and succinylcholine in pooled human plasma were compared. In addition, the rate of metabolism of mivacurium in buffered solutions of butyrylcholinesterase (E.C. 3.1.1.8) and acetylcholinesterase (E.C. 3.1.1.7) was determined. Succinylcholine concentrations were measured spectrophotometrically, and mivacurium concentrations were determined with a high-pressure liquid chromatographic assay. The hydrolysis of mivacurium in plasma followed first-order kinetics, and the rate of hydrolysis decreased as plasma was serially diluted. The Michaelis-Menten constant (Km) for mivacurium metabolism in plasma was 245 mumol/L, and the maximum velocity (Vmax) was 50 U/L; the Km for succinylcholine was 37 mumol/L, and Vmax was 74 U/L. At comparable multiples of the Km the hydrolysis rate of mivacurium was 70% of that of succinylcholine. Mivacurium was metabolized significantly in solutions containing butyrylcholinesterase, but only minimally in solutions containing acetylcholinesterase.

Butyrylcholinesterase↗
PubMed1989

Intravenous ranitidine antagonizes intense atracurium-induced neuromuscular blockade in rats.

The neuromuscular action of ranitidine, an H2-receptor antagonist, was investigated by determining its effect on atracurium-induced neuromuscular blockade in urethane-anesthetized and mechanically ventilated male Sprague-Dawley rats. An intravenous bolus and an infusion of atracurium were administered to produce a stable 93 +/- 5% (n = 11) neuromuscular blockade as judged by tibialis anterior muscle twitch response. Ranitidine administered as a 1, 5, or 10 mg/kg normal body weight IV bolus during continuous atracurium infusion produced marked antagonism of neuromuscular paralysis. The percentage of antagonism (25 +/- 9%; n = 4; 53 +/- 19%, n = 4; and 79 +/- 9%, n = 3, respectively) was linearly related to the dose of ranitidine (r = 0.86, P less than 0.05). These results suggest that IV ranitidine has a significant anticholinesterase action against atracurium-induced neuromuscular blockade.

Animals↗
PubMed1988

Pharmacokinetics of sufentanil in adolescent patients with chronic renal failure.

The role of the kidney in sufentanil elimination or metabolism has not been defined. The effects of chronic renal failure (CRF) on the pharmacokinetic profile of sufentanil were evaluated in six adolescent patients undergoing renal transplantation, and these findings were compared with data from age-matched control patients with normal renal function who were undergoing other surgical procedures. Patients with CRF weighed significantly less than did the control patients (28.7 +/- 5.7 vs 44.7 +/- 12.9 kg [mean +/- SD]). Although there was no statistical difference in the rate of clearance or apparent volume of distribution and half-life between the two groups, clearance and half-life were more variable among patients with CRF. In these patients, therefore, sufentanil dose must be carefully administered based on responses elicited in individual patients.

Adolescent↗
PubMed1988

Clinical pharmacology of doxacurium chloride (BW A938U) in children.

The neuromuscular effects of doxacurium were studied in 26 children during halothane-nitrous oxide-oxygen anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate the cumulative dose-response relation, nine patients received incremental doses of doxacurium (2.5-10 micrograms/kg); nine patients received 27.5 micrograms/kg (the estimated ED95); eight patients received 50 micrograms/kg (1.8 X ED95). The ED25, ED50, ED75, and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 11.5, 14.8, 19.0, and 27.3 micrograms/kg, respectively. Clinical duration (T25) was 27.8 +/- 10.3 (mean +/- SD) minutes at 1 X ED95 and 50.6 +/- 15.6 minutes at 1.8 X ED95. Time to recovery of the train-of-four ratio to 0.75 was 63.1 +/- 32.9 minutes at 1 X ED95 and 108.5 +/- 25.7 minutes at 1.8 X ED95. There were no significant changes in heart rate or mean arterial pressure after bolus administration of any dose of doxacurium.

Age Factors↗
PubMed1988

Mivacurium chloride (BW B1090U)-induced neuromuscular blockade during nitrous oxide-isoflurane and nitrous oxide-narcotic anesthesia in adult surgical patients.

The neuromuscular and cardiovascular effects of mivacurium were studied in 90 adult patients during nitrous oxide-oxygen-isoflurane (n = 45, ISO group) and nitrous oxide-oxygen-narcotic (n = 45, BAL group) anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relations, three subgroups of nine patients in the ISO group received mivacurium doses of 0.025, 0.03, and 0.04 mg/kg, respectively. Similarly, three subgroups of nine patients in the BAL group received mivacurium doses of 0.03, 0.04, and 0.05 mg/kg, respectively. The ED50 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose vs probit of maximum percentage depression of neuromuscular function. The estimated ED50 values for the ISO and BAL groups were 0.029 and 0.041 mg/kg, respectively. The estimated ED95 values for the ISO and BAL groups were 0.045 and 0.058 mg/kg, respectively. Recovery indexes were measured in 26 patients who received ED95 or greater doses of mivacurium in either the ISO or BAL groups. The recovery index was shorter in the BAL group (5.5 +/- 1.6 minutes [n = 10]), than in the ISO group (7.4 +/- 3.0 minutes [n = 16]). The addition of isoflurane (0.5-0.75% end-tidal concentration) to nitrous oxide-narcotic anesthesia augments the degree of neuromuscular blockade from a given dose of mivacurium and also prolongs the recovery index.

Adult↗
PubMed1988

Cimetidine does not inhibit plasma cholinesterase activity.

Cimetidine increases the duration of action of succinylcholine several-fold by an unknown mechanism. The hydrolysis rate of succinylcholine by human plasma was measured with a modified spectrophotometric assay. At a concentration of 1-50 micrograms/ml cimetidine did not inhibit the hydrolysis of succinylcholine. It is concluded that cimetidine may have an effect at the neuromuscular junction but does not inhibit plasma cholinesterase.

Cholinesterase Inhibitors↗