Effect of pre-eclampsia on plasma cholinesterase activity

Plasma cholinesterase (PCHE) activity was determined using a colorimetric method in 11 healthy non-pregnant women, 11 healthy pregnant women at term, and 11 pre-eclamptic pregnant women at term. The mean plasma cholinesterase activities for healthy non-pregnant women, healthy pregnant women and pre-eclamptic pregnant women were 438 +/- 81,257 +/- 25 and 173 +/- 18 units . ml-1, respectively. Our data suggest that there is a significant reduction in plasma cholinesterase activity in preeclamptic pregnant women when compared to healthy non-pregnant (p less than 0.001) and healthy pregnant women (p less than 0.001).     

Nicardipine reduces the cardio-respiratory toxicity of intravenously administered bupivacaine in rats

The purpose of our study was to examine the effect of intravenous (IV) nicardipine pretreatment (30 micrograms.kg-1), given three minutes before an IV bolus of bupivacaine to determine its effect on the incidence of fatal bupivacaine cardio-respiratory toxicity in adult male Sprague Dawley rats anaesthetized with intraperitoneal pentobarbital. Fifty rats were divided into four groups. Groups I and II (n = 10 each) received 3.5 mg.kg-1 0.5 per cent bupivacaine and Groups III and IV (n = 15 each) received 5.0 mg.kg-1, 0.5 per cent bupivacaine. Groups I and III received pretreatment with normal saline before bupivacaine, whereas Groups II and IV were given pretreatment with nicardipine, 30 mg.kg-1. There was no difference in the incidence of survival between the nicardipine pretreatment group and the saline placebo pretreatment group given 3.5 mg.kg-1, 0.5 per cent bupivacaine (no fatalities in either group). However, there was significant protection by nicardipine pretreatment in the group given 5 mg.kg-1, 0.5 per cent bupivacaine (13 of 15 survived, compared with only 4 of 15 in the saline pretreatment group, P less than 0.001). In conclusion, our data demonstrate that in rats given 0.5 per cent bupivacaine, 5 mg.kg-1, nicardipine pretreatment protected against fatal cardio-respiratory toxicity.     

Pseudocholinesterase activity in human cerebrospinal fluid

Pseudocholinesterase (PCHE) activity and dibucaine numbers (DN) in the cerebrospinal fluid (CSF) and plasma of 10 ASA physical status 1 and 2 patients were measured using a kinetic method. CSF had a mean PCHE activity of 0.018 +/- 0.013 unit/ml with a DN of 59 +/- 4. Whereas, PCHE activity and DN in the plasma were 0.960 +/- 0.12 units/ml and 84 +/- 3, respectively. We also measured PCHE activity and DN in the CSF and plasma of 4 patients in whom there was a recent history of intraventricular bleeding. These patients had a CSF PCHE activity of 0.340 +/- 0.07 units/ml (DN = 78 +/- 3) and a plasma PCHE activity of 0.950 +/- 0.10 units/ml (DN = 82 +/- 2). Our data show that there is a low activity of PCHE in CSF, 1/20-1/100th that of plasma. Our data also show that PCHE activity increased to 1/4 to 1/2 that of plasma in CSF of patients with bleeding into CSF.     

The effect of procainamide on plasma cholinesterase activity

The in vitro effect of procainamide on plasma cholinesterase (PCHE) activity in the plasma of ten normal ASA physical status I patients was studied using a kinetic method. The mean plasma cholinesterase activity without procainamide (control) was 0.90 +/- 0.09 units.ml-1. The dibucaine numbers of all the samples were in the normal range of 78 to 86, indicating normal genotypes. The mean plasma cholinesterase activity, in the presence of procainamide in concentrations of 5.0, 10.0, 20.0 and 40.0 micrograms.ml-1, was reduced to 0.73 +/- 0.04, 0.61 +/- 0.03, 0.45 +/- 0.02, and 0.36 +/- 0.01 units.ml-1, respectively. At therapeutic concentrations of 4 to 12 micrograms.ml-1, procainamide inhibited cholinesterase activity 15 to 30 per cent. The authors also showed that the concentration of procainamide required to inhibit 50 per cent of plasma cholinesterase activity was 20 micrograms.ml-1 (I50). The authors conclude that procainamide when tested in vitro had a statistically significant depressant effect on plasma cholinesterase activity at all the concentrations studied.     

The effects of inhibition of plasma cholinesterase and hepatic microsomal enzyme activity on cocaine, benzoylecgonine, ecgonine methyl ester, and norcocaine blood levels in pigs.

We measured the blood levels of cocaine and its three major metabolites, benzoylecgonine, ecgonine methyl ester, and norcocaine, in three groups of male pigs weighing about 26 kg (25.75 +/- 0.25 kg) to determine the effects of inhibition of plasma cholinesterase and hepatic microsomal enzyme activity on cocaine metabolism. In addition, systemic elimination half-life, volume of distribution, and clearance of cocaine were calculated for the three groups. Group 1 pigs (n = 4) were pretreated with normal saline solution, group 2 pigs (n = 4) were pretreated with tetraisopropyl pyrophosphoramide, a specific plasma cholinesterase inhibitor, and group 3 pigs (n = 4) were pretreated with cimetidine, a hepatic microsomal enzyme inhibitor, all administered intramuscularly. Pigs were anesthetized with intravenous sodium thiopental; a carotid arterial cannula and an external jugular catheter were then inserted for the administration of cocaine and for blood sampling. Forty-five minutes later, when pigs were again completely awake, cocaine 3 mg/kg was given intravenously. Arterial blood samples were collected for the analysis of cocaine and cocaine metabolite levels just before and at 5, 10, 15, 30, 45, 60, 120, 180, and 1440 minutes after the administration of cocaine. Cocaine and cocaine metabolite blood levels were analyzed with high-pressure liquid chromatography methods and plasma cholinesterase activity was measured with a colorimetric method. The blood levels of cocaine and cocaine metabolites were significantly different among the three groups (p less than 0.05, analysis of variance). Statistically significant differences in half-life, volume of distribution and clearance were also seen among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

The contribution of integrated PET/CT to the evolving definition of treatment volumes in radiation treatment planning in lung cancer

PURPOSE: Positron emission tomography (PET) with the glucose analog [18F]fluro-2-deoxy-D-glucose (FDG) has been accepted as a valuable tool for the staging of lung cancer, but the use of PET/CT in radiation treatment planning is still not yet clearly defined. By the use of (PET/computed tomography (CT) images in treatment planning, we were able to define a new gross treatment volume using anatomic biologic contour (ABC), delineated directly on PET/CT images. We prospectively addressed three issues in this study: (1) How to contour treatment volumes on PET/CT images, (2) Assessment of the degree of correlation between CT-based gross tumor volume/planning target volume (GTV/PTV) (GTV-CT and PTV-CT) and the corresponding PET/CT-based ABC treatment volumes (GTV-ABC and PTV-ABC), (3) Magnitude of interobserver (radiation oncologist planner) variability in the delineation of ABC treatment volumes (using our contouring method). METHODS AND MATERIALS: Nineteen patients with Stages II-IIIB non-small-cell lung cancer were planned for radiation treatments using a fully integrated PET/CT device. Median patient age was 74 years (range: 52-82 years), and median Karnofsky performance status was 70. Thermoplastic or vacuum-molded immobilization devices required for conformal radiation therapy were custom fabricated for the patient before the injection of [18]f-FDG. Integrated, coregistered PET/CT images were obtained and transferred to the radiation planning workstation (Xeleris). While the PET data remained obscured, a CT-based gross tumor volume (GTV-CT) was delineated by two independent observers. The PTV was obtained by adding a 1.5-cm margin around the GTV. The same volumes were recontoured using PET/CT data and termed GTV-ABC and PTV-ABC, correspondingly. RESULTS: We observed a distinct "halo" around areas of maximal standardized uptake value (SUV). The halo was identified by its distinct color at the periphery of all areas of maximal SUV uptake, independent of PET/CT gain ratio; the halo had an SUV of 2 +/- 0.4 and thickness of 2 mm +/- 0.5 mm. Whereas the center of our contoured treatment volume expressed the maximum SUV level, a steady decline of SUV was noted peripherally until SUV levels of 2 +/- 0.4 were reached at the peripheral edge of our contoured volume, coinciding with the observed halo region. This halo was always included in the contoured GTV-ABC. Because of the contribution of PET/CT to treatment planning, a clinically significant (> or =25%) treatment volume modification was observed between the GTV-CT and GTV-ABC in 10/19 (52%) cases, 5 of which resulted in an increase in GTV-ABC volume vs. GTV-CT. The modification of GTV between CT-based and PET/CT-based treatment planning resulted in an alteration of PTV exceeding 20% in 8 out of 19 patients (42%). Interobserver GTV variability decreased from a mean volume difference of 28.3 cm3 (in CT-based planning) to 9.12 cm3 (in PET/CT-based planning) with a respective decrease in standard deviation (SD) from 20.99 to 6.47. Interobserver PTV variability also decreased from 69.8 cm3 (SD +/- 82.76) in CT-based planning to 23.9 cm3 (SD +/- 15.31) with the use of PET/CT in planning. The concordance in treatment planning between observers was increased by the use of PET/CT; 16 (84%) had < or =10% difference from mean of GTVs using PET/CT compared to 7 cases (37%) using CT alone (p = 0.0035). Conclusion: Position emission tomography/CT-based radiation treatment planning is a useful tool resulting in modification of GTV in 52% and improvement of interobserver variability up to 84%. The use of PET/CT-based ABC can potentially replace the use of GTV. The anatomic biologic halo can be used for delineation of volumes.     

Effect of sevoflurane on P50 and on measurement of oxygen tension

Fresh samples of heparinized human blood from 10 healthy nonsmoking volunteers were used to study the effect of the inhaled anesthetic sevoflurane on the oxygen half-saturation pressure of hemoglobin (P₅₀) and on polarographic measurements of oxygen tension at low values. Control samples had a baseline P₅₀ of 26.9±0.2 mm Hg. When the blood samples were exposed to 1.75% (1 minimum alveolar concentration, MAC), 2.75%, and 3.5% (2 MAC) of sevoflurane, the P₅₀ values were 27.0±0.5 mm Hg, 27.1±0.4 mm Hg, and 26.9±0.5 mm Hg, respectively. Our present data show that 1 to 2 MAC sevoflurane has no significant effect on P₅₀ (P>0.05). Our data also show that sevoflurane did not interfere with polarographic measurements of oxygen tension (P>0.05). Other inhaled agents—halothane, enflurane, and isoflurane—do interfere with these measurements, and we cannot explain the difference.Presented at the annual meeting of the American Society of Anesthesiologists, Atlanta, GA, October 1987.     

The effects of neurokinin A, neurokinin B, and eledoisin on substance P analysis

Commercial sources for neuropeptide radioimmunoassays have made this sensitive tool available to clinical investigators for monitoring the potential involvement of neuropeptides in pain modulation. We measured substance P-like immunoreactivity in the plasma, saliva, and pericardial fluid of subjects with and without pain (chronic and acute) to determine if substance P levels are altered. Some recent studies have suggested that substance P in various body fluids may be a correlate of chronic pain. To test this correlation it is important to ensure that the assay is measuring what it was designed to measure. Therefore, the influence of three tachykinins on the analysis of substance P concentrations was assessed with a commercially available radioimmunoassay kit. A small (approximately 2 to 6%), apparently nonspecific elevation in measured substance P was found when alpha-neurokinin, beta-neurokinin, or eledoisin was incubated with substance P and its antibody. Our results also indicate an apparent specific affinity of the substance P antibody for alpha-neurokinin (above 1,000 pg/ml) and beta-neurokinin (above 5,000 pg/ml). Substance P levels in the body fluids we tested ranged from 0.47 to 62.88 pg/mg protein (47.4 to 230.8 pg/ml). Levels of the tested tachykinins have not been determined in body fluids. If alpha-neurokinin or beta-neurokinin is found to be present in high concentrations in these fluids, this commercially available substance P kit may overestimate substance P levels. The concentrations of tachykinins necessary to interfere specifically with the assay are 10- to 100-fold higher than substance P in body fluids. If the other tachykinins are present at concentrations similar to the substance P levels, we would not expect them to interfere substantially with the accuracy of our measurements of substance P using this assay.This study was funded in part by the Study Center for Anesthesiology Toxicology, Vanderbilt University Medical Center, Nashville, TN.We thank Incstar Corporation, Stillwater, MN, for providing the substance P radioimmunoassay kits.     

Cimetidine does not affect plasma cholinesterase activity

Blood samples were drawn from 10 ASA physical status 1 and 2 patients before (baseline) and after the administration of cimetidine to determine the in vivo effect of cimetidine on plasma cholinesterase (PCHE) activity. The in vitro effects of cimetidine at different plasma concentrations were also studied using the same blood samples. PCHE activity in the baseline samples was 432 +/- 4.6 (mean +/- SEM) U/ml, the dibucaine number 82. Administration of oral cimetidine (300 mg) the night before and 2 hours before surgery, failed to have any effect on PCHE activity (no in vivo effect). Plasma cholinesterase activity in the presence of cimetidine in vitro at plasma concentrations of 1.5, 15, 150, and 1500 micrograms/ml was 428, 420, 397, and 177 U/ml, respectively. Thus, in vitro data showed that cimetidine at plasma concentrations (1.5 to 15 micrograms/ml) achieved with clinical doses also has no effect on PCHE activity.     

Substance P level is increased in the cholesterol induced anaphylactoid reaction in the pig

The role of substance P (SP) in cholesterol-induced anaphylactoid reaction was investigated in 13 Landrace pigs. Pigs were anesthetized with sodium thiopental and ventilation was controlled with 70% nitrous oxide in oxygen. A Swan-Ganz catheter and a carotid arterial line were placed to monitor the hemodynamic data. Group 1 pigs (control group,n=5) each received 20 ml of intravenous (IV) colloid infusion solution (Haemaccel) and group 2 pigs (cholesterol group,n=8) each received an IV injection of pure cholesterol emulsion (12 mg/kg) in 20 ml of Haemaccel. Blood samples for SP and histamine (H) levels were taken just before and for 10 min following the placebo, Haemaccel, and cholesterol injections. Urine samples were also collected just before and at 60 min following the injections for methyl histamine (MH) levels. Group 2 pigs (cholesterol) developed an anaphylactoid reaction as indicated by marked and significant hemodynamic changes. None of the group 1 (placebo) pigs developed an anaphylactoid reaction. Significant increases in blood SP and H levels (P<0.05), and urine MH levels (P<0.05) were seen in cholesterol-treated pigs (group 2), whereas no significant changes were seen in control pigs (group 1). Our results suggest that SP is involved in the cholesterol-induced anaphylactoid reaction in pigs.