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Biomedical subjects

D R Cook

Publications and source records attributed to D R Cook.

At least 37 records · Page 2Linked to original sources
PubMed1993

Fibroblast growth factor, epidermal growth factor, insulin-like growth factors, and platelet-derived growth factor-BB stimulate proliferation of clonally derived porcine myogenic satellite cells.

Clonally derived cultures of porcine skeletal muscle satellite cells were developed. The mitogenic effects of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factors (IGF-I and -II), and platelet-derived growth factors (PDGF-AA and -BB) were examined. Individually, bFGF, IGFs, and PDGF-BB stimulated proliferation of porcine satellite cells grown in basal serum-free medium or Minimum Essential Medium containing 2% fetal bovine serum (MEM-2% FBS). EGF stimulated proliferation in MEM-2% FBS, but neither EGF nor PDGF-AA were mitogenic when added to serum-free medium. The interactions among bFGF, EGF, IGF-I, and PDGF-BB were examined in serum-free medium, using growth factor concentrations shown in dose-response experiments to induce maximal proliferative responses (10 ng/ml bFGF, EGF and PDGF-BB, and 50 ng/ml IGF-I). The combination of bFGF and IGF-I dramatically increased proliferation, and IGF-I also synergized with EGF to increase proliferation. EGF, IGF-I, and bFGF interacted with PDGF-BB to stimulate proliferation. With the exception of EGF and bFGF, combinations of two growth factors typically resulted in greater than additive responses. Simultaneous exposure of satellite cells to bFGF, PDGF-BB, EGF, and IGF-I produced a fivefold increase in DNA compared to cells grown in basal serum-free medium. Elimination of EGF did not reduce the mitogenic response, yet removal of IGF-I, bFGF, or PDGF-BB reduced proliferation by approximately 40, 20, and 10%, respectively. These mitogens are likely physiological regulators of porcine satellite cell activity.

Animals↗
PubMed1993

Long-term inhibition of clinical and laboratory human immunodeficiency virus strains in human T-cell lines containing an HIV-regulated diphtheria toxin A chain gene.

The human immunodeficiency virus (HIV) causes persistent infection of T cells. Chemotherapy for infection in humans may slow HIV-related disease progression, but it does not eradicate virus. Thus, other treatment modalities are warranted. We have previously demonstrated that the human T cell line H9, ordinarily permissive for HIV infection, may be protected against infection with the LAI strain of HIV by intracellular immunization with the gene encoding diphtheria toxin A chain (DT-A) under the control of HIV Tat and Rev. Cloned cells were protected for up to 6 days in vitro. We now report protection against the LAI laboratory isolate for up to 59 days, and against clinical HIV strains of differing phenotypic properties and cell tropisms for up to 59 days. In some cases, protection was complete in that no residual HIV was detected by HIV p24 antigen production, co-culture with parental H9 cells, or the polymerase chain reaction (PCR). CD4+ surface expression of DT-A transduced cloned H9 cells was similar to parental H9 in most cases. These results suggest that toxin gene therapy for HIV infection may ultimately be feasible.

CD4 Antigens↗
PubMed1993

Clinical pharmacology of mivacurium in pediatric patients less than off years old during nitrous oxide-halothane anesthesia.

We determined the dose-response relationship of mivacurium in infants 2-6 and 7-11 mo of age during nitrous oxide-halothane anesthesia. The neuromuscular and cardiovascular effects of a bolus dose of mivacurium larger than the ED95 in infants and young children from 2-23 mo of age were observed. The infusion rate of mivacurium required to maintain approximately 95% neuromuscular block was determined. There was no significant difference between the estimated dose-response relationship in infants 2-6 mo and that in infants 7-11 mo. The ED50 and ED95 were 44 micrograms/kg and 85 micrograms/kg for infants 2-11 mo (n = 70), r = 0.53. A bolus dose of 150 micrograms/kg mivacurium in infants (2-6 mo) produced 100% depression of the initial twitch height (T1) in 8 out of 9 infants and 85% depression in 1 infant. The time to onset of maximum block was 1.6 +/- 0.3 (0.7-2.7) (mean, SEM [range]) min, and time to recovery to 25% of T1 (T25) was 7.5 +/- 0.7 (5.5-11) min after 150 micrograms/kg in these patients. A bolus dose of 200 micrograms/kg mivacurium in infants and young children (7-23 mo) produced 100% depression of T1 in 14 of 17 patients, 97% depression in 2, and 90% depression in 1. The time to onset of maximum block was 1.5 +/- 0.1 (0.8-3) min and T25 was 10.3 +/- 1.5 (4.8-30.5) min after 200 micrograms/kg in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

Validity of a disposable end-tidal CO2 detector in verifying endotracheal tube placement in infants and children.

STUDY OBJECTIVE: To examine the validity of a disposable, colorimetric end-tidal CO2 detector in verifying endotracheal tube (ETT) placement in infants and children. DESIGN: The detector was studied prospectively in 151 intubations. SETTING: Operating room, ICU, and emergency department of a children's hospital. PARTICIPANTS: One hundred thirty-seven children undergoing endotracheal intubation for anesthesia (52), respiratory support (76), or CPR (23). INTERVENTIONS: After endotracheal intubation, tube position was verified, the detector was attached, and readings were obtained. MEASUREMENTS AND RESULTS: The detector correctly identified tube position (trachea, 124; esophagus, four) in all 120 patients who were not in cardiac arrest (P less than .01). In the cardiac arrest setting, all six esophageal intubations were correctly identified, but two of the 17 tracheal intubations were incorrectly interpreted as esophageal intubations (P less than .01). CONCLUSION: The detector accurately identifies ETT position in children with spontaneous circulation who weigh more than 2 kg. During CPR, a positive test correctly indicates that the ETT is in the airway, but a negative result (suggesting esophageal placement) requires an alternate means of confirming ETT position.

Adolescent↗
PubMed1992

Pharmacokinetics of mivacurium in normal patients and in those with hepatic or renal failure.

We have determined the pharmacokinetics and duration of action of a bolus dose of mivacurium (0.15 mg kg-1) during isoflurane and nitrous oxide anaesthesia in nine patients with normal renal and liver function, nine patients undergoing cadaveric kidney transplantation and nine patients undergoing cadaveric liver transplantation. Total plasma concentrations of mivacurium were measured for 2.5 h after administration using a high-pressure liquid chromatographic assay. Plasma concentration vs time data for what were presumed to be the two active mivacurium isomers were analysed by a non-compartmental method based on statistical moments. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The mean time to recovery of 25% neuromuscular transmission, T25, was greater in the patients with liver failure (57.2 min) than in control patients (18.7 min). The volume of distribution at steady rate (Vdss) was comparable in the three groups. Patients with impaired liver function had significantly longer mean residence time and smaller plasma clearance than did patients with renal failure or control patients. There were significant negative correlations between plasma cholinesterase activity and both T25 (r = 0.79) and mean residence time (r = 0.62).

Adult↗
PubMed1992

Effects of bolus administration of ORG-9426 in children during nitrous oxide-halothane anesthesia.

ORG-9426 is a new steroidal nondepolarizing neuromuscular blocking drug. We determined the dose-response relationship of ORG-9426 in 62 children (aged 1-5 yr) during nitrous oxide-halothane anesthesia by means of log-probit transformation and least-squares linear regression of the initial dose and response. Twelve additional patients received a bolus of 600 micrograms/kg (2 X the dose estimated to produce 95% depression of neuromuscular function [ED95]) of ORG-9426. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. To determine the dose-response relationship, patients randomly received initial bolus doses of 120 (n = 15), 160 (n = 16), 200 (n = 16), or 240 (n = 15) micrograms/kg ORG-9426. The resulting dose estimated to produce 50% depression of neuromuscular function (ED50) and ED95 were 179 and 303 micrograms/kg, respectively. Time from administration of 600 micrograms/kg to onset of 90% and 100% neuromuscular block was 0.8 +/- 0.1 (0.5-1.3) and 1.3 +/- 0.2 (0.7-2.8) min. The time to recovery of neuromuscular transmission to 25% (T25) was 26.7 +/- 1.9 (17.2-39.0) min. The recovery index (T25-75) was 11.0 +/- 1.6 (6.0-22.8) min, and the time to complete recovery of the magnitude of the fourth response to a train-of-four stimuli divided by the magnitude of the first response (T4/T1) greater than or equal to 0.75 was 41.9 +/- 3.2 (26.5-57.7) min.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstanols↗
PubMed1991

Safety and efficacy of alfentanil and halothane in paediatric surgical patients.

Alfentanil, a congener of the opioid fentanyl, possesses properties that make it an attractive choice for use during short operative procedures. Since the pharmacodynamic aspects of alfentanil have not been well documented in children, this study was undertaken to evaluate the safety, efficacy, and dose requirements of alfentanil when used with nitrous oxide or halothane in paediatric patients. Eighty unpremedicated patients, ASA physical status I or II and aged 2-12 yr were studied. Patients were randomly assigned to one of four groups. After induction of anaesthesia with nitrous oxide, oxygen, and halothane, the groups were treated as follows. In Group 1 (n = 19), after halothane was discontinued, alfentanil 50 micrograms.kg-1 was infused over 30 sec. In Group 2 (n = 20), the end-tidal halothan was maintained at 0.5% and alfentanil 25 micrograms.kg-1 was infused. In Group 3 (n = 20), the end-tidal halothane concentration was maintained at 1% and alfentanil 12.5 micrograms.kg-1 was infused. In Group 4 (n = 21), the end-tidal halothane concentration was maintained at 1.5% and no alfentanil was administered. Patients in Groups 1, 2, and 3 received bolus doses of alfentanil 12.5 micrograms.kg-1 as needed to maintain haemodynamic stability. After alfentanil administration, there were transient decreases in systolic blood pressure in Groups 1 and 2, and in heart rate in Group 2. With surgical stimulation, haemodynamic stability was well maintained except in patients in Group 1, who had an increase in systolic blood pressure. Children Group 1 were alert sooner and their tracheas were extubated earlier than those in Groups 2, 3, and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗
PubMed1991

Hemodynamic performance and histamine levels after desmopressin acetate administration following cardiopulmonary bypass in adult patients.

Sixteen patients undergoing cardiac surgical procedures were prospectively randomized into two groups to study the hemodynamic and histamine-releasing effects of desmopressin acetate (DDAVP) administration after cardiopulmonary bypass. Ten minutes after administration of protamine for reversal of heparin, DDAVP, 0.3 microgram/kg, was infused intravenously over 5 seconds in group 1, and the same dose of DDAVP was administered over 5 minutes as an infusion in group 2. There were no statistical differences between baseline values in groups 1 and 2. DDAVP decreased mean arterial pressure by 30% and 25% in groups 1 and 2 (69 +/- 5 mm Hg to 52 +/- 8 mm Hg, P less than 0.005, and 79 +/- 20 mm Hg to 55 +/- 8 mm Hg, P less than 0.005), respectively. The hypotension in both groups was related to decreases in systemic vascular resistance (1,616 +/- 262 dyne.s.cm-5 to 1,073 +/- 199 dyne.s.cm-5, P less than 0.005, and 1,850 +/- 541 dyne.s.cm-5 to 1,144 +/- 214 dyne.s.cm-5, P less than 0.005). Phenylephrine infusion successfully treated the DDAVP-induced hypotension in all patients. Arterial histamine levels at 3 and 5 minutes after infusion of DDAVP did not differ significantly from baseline values. It is concluded that DDAVP at 0.3 microgram/kg is a potent vasodilator when administered intravenously and that histamine is not involved in producing its hypotensive effects.

Anesthesia, Intravenous↗
PubMed1991

Double-blind comparison of oral transmucosal fentanyl citrate with oral meperidine, diazepam, and atropine as preanesthetic medication in children with congenital heart disease.

The effectiveness of oral transmucosal fentanyl citrate (OTFC) as preanesthetic medication was compared with oral meperidine, diazepam, and atropine (MDA) in 40 pediatric patients scheduled to undergo repair of congenital heart defects. In a double-blinded manner, patients received a fentanyl lollipop (20-25 micrograms/kg) and a placebo oral solution (0.4 ml/kg) (n = 20) or a placebo lollipop and an oral solution (0.4 ml/kg) of meperidine (1.5 mg/kg), diazepam (0.2 mg/kg), and atropine (0.02 mg/kg) (n = 20). The patient's vital signs, systolic and diastolic blood pressures, heart rate, respiratory rate, and oxyhemoglobin saturation (SpO2), as well as activity and apprehension scores were evaluated and recorded at baseline and at 10-min intervals. The patient's emotional status at the time of parental separation and at induction of anesthesia were also assessed. Side effects and onset of action were observed. After OTFC, onset of sedation was significantly faster than with the oral solution of meperidine, diazepam, and atropine. In both groups there was no significant change in heart rate. Although systolic blood pressure, diastolic blood pressure, and respiratory rate showed statistically significant decreases, these changes were not clinically significant. The child's emotional status at the time of separation from the parents and during induction was similar in both groups. Side effects with OTFC were more frequent: nose itching occurred in 65%, body itching in 10%, and vomiting in 30%. Two patients (10%) in the OTFC-treated group became hypoxemic (SpO2 less than 90) and required supplemental oxygen. In the group receiving oral meperidine, diazepam, and atropine, 10% had mild facial pruritus and 5% complained of a dry mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Effects of famotidine on gastric pH and residual volume in pediatric surgery.

Aspiration pneumonitis is a severe complication of anesthesia. The objectives of this study were to determine if preoperative famotidine, a new histamine2-receptor antagonist, given by mouth either the evening before or the morning of elective surgery, reduced gastric residual volume and increased gastric pH in pediatric patients. Either famotidine or placebo (or both) were orally administered to 58 children (aged 2-17 years). The patients were randomly assigned to four groups: Famotidine-Famotidine, Placebo-Placebo, Placebo-Famotidine, and Famotidine-Placebo; subjects in the Famotidine-Famotidine group received two doses of famotidine (0.5 mg.kg-1 per dose), those in the Placebo-Placebo group, two doses of placebo, those in the Placebo-Famotidine and Famotidine-Placebo group, one dose of each by mouth. The Famotidine-Famotidine group received one dose of famotidine at 22:00 the evening before surgery and a second dose 60-90 min before the scheduled time of surgery. The Placebo-Placebo group received two doses of placebo at the same times as the Famotidine-Famotidine group. The Placebo-Famotidine group received a dose of placebo the night before surgery and a dose of famotidine the morning of surgery; the Famotidine-Placebo group received famotidine the night before surgery and placebo the morning of surgery. The administration of famotidine on the morning of surgery significantly increased gastric pH (4.8 vs. 1.3) in comparison with placebo, as did two doses of famotidine (6.6). Famotidine failed to reduce gastric residual volume significantly in any group. The administration of famotidine significantly reduced the number of pediatric patients considered at higher risk for aspiration pneumonitis, despite not decreasing gastric residual volume.

Administration, Oral↗
PubMed1991

Oral transmission of transmissible gastroenteritis virus by muscle and lymph node from slaughtered pigs.

A study was conducted in the USA to determine whether transmissible gastroenteritis (TGE) virus could be transmitted from carcases of slaughtered pigs. Transmissible gastroenteritis virus was transmitted to 6-day-old piglets by dosing with homogenates of muscle and lymph node collected from 500 clinically normal pigs at the time of slaughter. All piglets in 2 separately housed litters showed clinical signs of TGE with 5 piglets dying within 10 d of oral dosing with homogenates. Transmissible gastroenteritis virus was isolated from 2 of these piglets and all piglets developed TGE antibody. Transmissible gastroenteritis virus was not isolated in tissue culture from muscle and lymph node homogenates, but was isolated from 4 (0.8%) of 500 tonsil samples collected from the same pigs. A survey of 250 serum samples provided an estimate of the prevalence of slaughtered pigs with TGE antibody of 34.8% in the sample population. The results indicate that carcases of some pigs from TGE endemic areas contain viable TGE virus, and that there would be a substantial risk of introducing TGE virus into Australia by the importation of uncooked pig meat from these areas.

Administration, Oral↗
PubMed1991

Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure.

We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Vecuronium infusion requirements in children during halothane-narcotic-nitrous oxide, isoflurane-narcotic-nitrous oxide, and narcotic-nitrous oxide anesthesia.

We were interested in determining the infusion rate of vecuronium required to maintain approximately 95% neuromuscular blockade in children during halothane-narcotic-nitrous oxide (0.8% end-tidal concentration), isoflurane-narcotic-nitrous oxide (1.0% end-tidal concentration), or narcotic-nitrous oxide anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Effective vecuronium infusion requirements averaged 1.5 +/- 0.1 micrograms.kg-1.min-1 (mean +/- SEM) during isoflurane-narcotic-nitrous oxide anesthesia, 1.9 +/- 0.1 micrograms.kg-1.min-1 during halothane-narcotic-nitrous oxide anesthesia, and 2.4 +/- 0.3 micrograms.kg-1.min-1 during narcotic-nitrous oxide anesthesia. Infusion requirements significantly decreased after the first 30 min of infusion in the presence of both potent inhalation anesthetics, but did not change with time during narcotic-nitrous oxide anesthesia. There was no evidence of decreasing infusion requirements during prolonged vecuronium infusion (2.5 h). There was no difference in the rate of spontaneous or pharmacologically induced recovery between anesthetic groups. The mean recovery index (T25-75) after termination of the infusion was 13.7 min.

Anesthesia, General↗
PubMed1991

Alfentanil pharmacokinetics in piglets with increased intra-abdominal pressure.

Increased intra-abdominal pressure (IAP) occurs in pediatric patients with end-stage liver disease and ascites, as well as in children following surgery for diaphragmatic hernia, omphalocele, gastroschisis and orthotopic liver transplantation. Although the hemodynamic response to increased IAP is well described, little information is available regarding the effects of IAP on drug distribution and elimination. We studied the effects of increased IAP (20 mm Hg) on the pharmacokinetics of alfentanil in piglets and compared these findings with those in control animals. Increased IAP appears to have no significant effect on the volume of distribution (0.46 +/- 0.06 vs. 0.61 +/- 0.23 liter/kg), mean residence time (68.8 +/- 27.8 vs. 62.3 +/- 27.8 min) and elimination half-life (47.7 +/- 19.0 vs. 43.2 +/- 19.3 min).

Abdomen↗
PubMed1990

A brief technical communication: detection of fentanyl in urine.

A reliable and sensitive method to analyze fentanyl in urine was developed using radioimmunoassay (RIA). Fentanyl, a highly lipophilic drug (pKa 7.7), has become a common drug of abuse. We evaluated three analytical techniques to detect fentanyl in urine. This paper reports the best of the three - a modified solvent extraction combined with a fentanyl RIA.

Fentanyl↗