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Biomedical subjects

C E Smith

Publications and source records attributed to C E Smith.

At least 217 records · Page 12Linked to original sources
PubMed1988

The incidence of prebypass dysrhythmias in patients undergoing coronary artery surgery.

The incidence of dysrhythmias during the prebypass period of coronary artery surgery has not been accurately reported. Using Holter monitoring of the electrocardiogram, this study was undertaken to determine the incidence of dysrhythmias and ischemia and their relationship to specific events during the prebypass period. The role of preoperative calcium entry blockers (CEB), beta-adrenergic blockers (BB), or both on the incidence of dysrhythmias and ischemia was also studied. One hundred thirty-eight patients were premedicated with morphine, scopolamine, and diazepam. Anesthesia was induced with fentanyl or sufentanil followed by either pancuronium or vecuronium and maintained with sufentanil or enflurane. All 138 patients experienced a dysrhythmia during the prebypass period. Seventy-five percent of the patients had at least one episode of a supraventricular dysrhythmia (SVD), 39% had a sinus bradycardia, and 20% had a conduction abnormality. Ninety-two percent of the patients had premature ventricular contractions (PVC) and, surprisingly, 76% had non-sustained ventricular tachycardia. One patient developed ventricular fibrillation and one had ventricular tachycardia. The peak incidence of dysrhythmias occurred at insertion of the pulmonary artery (PA) catheter and at aortic dissection. The incidence of prebypass ischemia was 18%, but these patients did not have a higher incidence of ventricular dysrhythmias. Preoperative CEBs and BBs did not influence the incidence of ischemia or dysrhythmias with the exception of SVD; there was a significantly lower incidence at PA catheterization in patients taking CEBs preoperatively (P < .05). It can be concluded that dysrhythmias are very common during the prebypass period. The low rate of progression to life-threatening dysrhythmias may be related to the fact that the majority occurred during mechanical stimulation and that patients were chronically taking CEBs and/or BBs preoperatively.

Adrenergic beta-Antagonists↗
PubMed1988

Cumulative dose-response with infusion: a technique to determine neuromuscular blocking potency of atracurium and vecuronium.

The ability of cumulative dose-response techniques to obtain accurate data is most likely limited by redistribution and elimination of the drug during the study period. Therefore the usefulness of these techniques would be improved by replacing the amount of drug lost. This hypothesis was assessed for the intermediate-duration neuromuscular blockers vecuronium and atracurium, and calculations were made based on a pharmacokinetic model with an effect compartment. Sixty patients received either single doses (SD) (n = 36), cumulative doses (CD) (n = 12), or CD of vecuronium or atracurium with an infusion (CDI) to replace eliminated or redistributed drug (n = 12). The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade at the adductor pollicis and log dose. The potencies obtained with all three methods were within 20% of each other. For vecuronium the ED90 was (mean +/- SE) 0.034 +/- 0.002 (SD), 0.037 +/- 0.003 (CD), and 0.036 +/- 0.003 mg/kg (CDI). For atracurium the ED90 was 0.175 +/- 0.009 (SD), 0.206 +/- 0.019 (CD), and 0.179 +/- 0.015 mg/kg (CDI). Calculated values corresponded well with measured values. The calculations predicted that the agreement between single- and cumulative-dose techniques would be improved if (1) the dose increment was increased, (2) the elimination half-life was increased above 20 minutes, or (3) an infusion was added.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Potency of atracurium and vecuronium at the diaphragm and the adductor pollicis muscle.

Train-of-four stimulation was applied to the ulnar and phrenic nerves in 18 adult patients anaesthetized with nitrous oxide and halothane in oxygen. The response of the adductor pollicis and the diaphragm were measured. Incremental doses of atracurium and vecuronium were given, with an infusion to replace drug lost by elimination or distribution. The mean (SEM) doses of atracurium associated with 50% and 90% depression of response to the first stimulation in the train-of-four (ED50 and ED90) were 90 (9) and 133 (10) micrograms kg-1 at the adductor pollicis, and 130 (9) and 245 (17) micrograms kg-1 at the diaphragm, respectively. The mean (SEM) ED50 and ED90 of vecuronium were 25 (2) and 38 (4) micrograms kg-1 at the adductor pollicis and 34 (3) and 58 (5) micrograms kg-1 at the diaphragm, respectively. The mean (SEM) ED50 ratios were 1.56 (0.16) for atracurium and 1.47 (0.16) for vecuronium. ED90 ratios were 1.93 (0.29) and 1.55 (0.17) for atracurium and vecuronium, respectively. It is concluded that both atracurium and vecuronium exhibit a similar degree of sparing of the diaphragm.

Adult↗
PubMed1988

Bronchial leukocyte proteinase inhibitor levels in bronchial washings in asthma patients.

To evaluate whether epithelial damage of airways in asthma could be related to diminished levels of the low molecular weight bronchial leukocyte proteinase inhibitor (BLPI) in airways, we determined BLPI in bronchial washings of 13 asthma patients and 13 healthy subjects, using a sensitive enzyme-linked immunoassay. The patients had asthma due to western red cedar and had bronchial washings done 24 to 48 hours after a mild to moderate asthmatic reaction induced by inhalation challenge. We did not find significant differences in BLPI concentrations in lavage fluid of asthma patients and healthy control subjects. The ratios of BLPI to albumin levels in bronchial washings appeared to be lower among asthmatic patients, but this difference was mainly due to an increase in albumin levels in lavage fluid in asthma. In addition, there were no significant differences in BLPI levels in washings obtained from main and segmental bronchi in both control subjects and asthma patients.

Adult↗
PubMed1988

Dose-response curves for succinylcholine: single versus cumulative techniques.

This study was performed to determine the potency of succinylcholine using the single-dose technique, and to test the ability of the cumulative dose technique for generating dose-response data. Thirty-eight adult patients received single doses (n = 18), cumulative doses (n = 10), or cumulative doses of succinylcholine with an infusion to replace metabolized drug (n = 10). During opiate-thiopental-nitrous oxide anesthesia the force of contraction of the adductor pollicis in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade and log dose. Similar potencies were obtained with single dose and cumulative dose with infusion techniques with an ED90 of 0.27 +/- 0.03 and 0.26 +/- 0.02 mg/kg (mean +/- SEM) respectively. However, cumulative dose without infusion significantly underestimated potency with an ED90 of 0.42 +/- 0.06 mg/kg (P less than 0.05 compared with the other two techniques). It is concluded that cumulative dose techniques can be accurately employed to determine the potency of succinylcholine if an infusion is utilized to compensate for eliminated drug. The data suggest that clinically used doses of succinylcholine (1.0-1.5 mg/kg) are equivalent to 3-5 times the ED90 and may explain the excellent intubating conditions provided by this drug.

Adult↗
PubMed1988

Potency of succinylcholine at the diaphragm and at the adductor pollicis muscle.

To quantify the differential effect of succinylcholine at the diaphragm and the adductor pollicis muscle, 10 patients were studied during halothane-nitrous oxide anesthesia. Train-of-four stimulation was applied to the ulnar and phrenic nerves. The force of contraction and the electromyographic response of the adductor pollicis were measured and compared with the diaphragmatic electromyogram. Then dose-response curves for both muscles were constructed using incremental doses of succinylcholine with an infusion to replace metabolized or redistributing drug. Linear regressions were obtained between the logit transformation of neuromuscular blockade at the adductor pollicis and diaphragm and the logarithm of the dose. The diaphragm was relatively resistant to succinylcholine. At 90% adductor pollicis block, the diaphragm was only (mean +/- SEM) 37 +/- 3% blocked. The diaphragm required 1.8 +/- 0.2 times as much succinylcholine as the adductor pollicis for an identical 90% block. The ED50 and ED90 values for succinylcholine at the diaphragm were 0.23 +/- 0.04 and 0.40 +/- 0.09 mg/kg, respectively. Corresponding values for the adductor pollicis were 0.14 +/- 0.01 and 0.21 +/- 0.02 mg/kg. The data indicate that the degree of adductor pollicis blockade might overestimate the intensity of diaphragmatic paralysis.

Anesthesia, Inhalation↗
PubMed1987

The initial phase of GnRH-stimulated LH release from pituitary cells is independent of calcium entry through voltage-gated channels.

Kinetic studies on gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release were undertaken using rat and chicken pituitary cell cultures. In response to continuous GnRH stimulation, a biphasic pattern of LH release was demonstrated. The two phases showed different susceptibility to the voltage-gated Ca2+ channel blockers D600 and nifedipine. The first (transient) phase of LH release was unaffected by the Ca2+ channel blockers whereas the second (sustained) phase was inhibited by both drugs. These results indicate that the initial phase of LH release is independent of Ca2+ entry through voltage-gated Ca2+ channels and may depend on mobilisation of intracellular Ca2+ or entry of extracellular Ca2+ through another mechanism.

Animals↗
PubMed1987

Properties of a GTP sensitive microdomain in rough microsomes.

Stripped rough microsomes (SRM) fuse when incubated with physiological concentrations of GTP and MgCl2. In order to examine further to what extent such fusions are associated with other membrane functions of rough endoplasmic reticulum, we have evaluated the role of cytosolically exposed peptide constituents of SRM in fusion, and the possible relationship of GTP/MgCl2-induced fusion in protein transport across endoplasmic reticulum (ER) membranes, and in ER-Golgi interactions. Controlled proteolytic digestion of SRM led to the loss of fusion capability at 15 micrograms/ml trypsin--a concentration which maintained the latency of intraluminal mannose-6-phosphatase. Hence, a cytosolically exposed protein(s) regulated fusion. Based on ribonuclease-induced ribosome capping experiments, it was further concluded that the cytosolic oriented protein(s) was sequestered beneath the ribosome. As co-translational cell free translocation of placental lactogen across SRM was similar in control membranes compared to those rendered incapable of fusing, it was concluded that the fusion phenomenon may not be related to translocation. Under conditions promoting homologous fusion of SRM or Golgi membranes, mixtures of the two membranes showed no heterologous membrane fusion as assessed morphologically or by the transport of newly synthesized membrane glycoprotein. These experiments attest to the specificity of cytosolically exposed protein(s) in regulating nucleotide/divalent cation-induced membrane fusion.

Animals↗
PubMed1987

Ozone effects on inhibitors of human neutrophil proteinases.

The effects of ozone on human alpha 1-proteinase inhibitor (A-1-PI), alpha 1-antichymotrypsin (A-1-Achy), bronchial leukocyte proteinase inhibitor (BLPI), and Eglin C were studied using in vitro exposures in phosphate-buffered solutions. Following ozone exposure, inhibitory activities against human neutrophil elastase (HNE) and/or cathepsin G (Cat G) were measured. Exposure of A-1-PI to 50 mol O3/mol protein resulted in a complete loss of HNE inhibitory activity, whereas A-1-Achy lost only 50% of its Cat G inhibitory activity and remained half active even after exposure to 250 mol of O3. At 40 mol O3/mol protein, BLPI lost 79% of its activity against HNE and 87% of its Cat G inhibitory activity. Eglin C, a leech-derived inhibitor, lost 81% of its HNE inhibitory activity and 92% of its ability to inhibit Cat G when exposed to 40 mol O3/mol. Amino acid analyses of ozone-exposed inhibitors showed destruction of Trp, Met, Tyr, and His with as little as 10 mol O3/mol protein, and higher levels of O3 resulted in more extensive oxidation of susceptible residues. The variable ozone susceptibility of the different amino acid residues in the four proteins indicated that oxidation was a function of protein structure, as well as the inherent susceptibility of particular amino acids. Exposure of A-1-PI and BLPI in the presence of the antioxidants, Trolox C (water soluble vitamin E) and ascorbic acid (vitamin C), showed that antioxidant vitamins may protect proteins from oxidative inactivation by ozone. Methionine-specific modification of BLPI reduced its HNE and Cat G inhibitory activities. Two moles of N-chlorosuccinimide per mole of BLPI methionine caused an 80% reduction in activity against Cat G, but only a 40% reduction in HNE inhibitory activity.

Amino Acids↗
PubMed1987

Immunocytochemical and radioautographic evidence for secretion and intracellular degradation of enamel proteins by ameloblasts during the maturation stage of amelogenesis in rat incisors.

In the continuously erupting rat incisor the ameloblasts progress through distinct stages associated with the secretion and maturation of enamel. We have examined the possibility that the so-called "postsecretory" ameloblasts of the maturation stage of amelogenesis remain biosynthetically active and are engaged in the synthesis, secretion, and degradation of enamel gene products. The ultrastructural distribution of antigenic sites for enamel proteins was studied within enamel organ cells during the early maturation stage of amelogenesis in rat incisors by using the protein A-gold immunocytochemical technique and rabbit polyclonal antibodies developed against mouse amelogenins. All regions of amelogenesis from late secretion through the first complete modulation from ruffle-ended to smooth-ended ameloblasts were examined. Specific immunolabelling was found within the rough endoplasmic reticulum, Golgi saccules, secretory granules, and lysosomes of ameloblasts throughout these regions. The heaviest intracellular immunolabelling was found within secretory granules and lysosomes (multivesicular type). Quantitative analyses showed that the Golgi saccules and the multivesicular lysosomes of modulating ameloblasts were generally less immunoreactive compared to similar organelles in ameloblasts secreting the inner enamel layer. Radioautographic studies confirmed that ameloblasts of the maturation stage incorporated 3H-leucine and 3H-methionine and secreted labelled proteins into the enamel layer. Grain counts indicated that ameloblasts from the first ruffle-ended band incorporated about two-fold less 3H-methionine and secreted about tenfold less labelled proteins into the enamel compared to ameloblasts secreting the inner enamel layer. The results of this study confirm that ameloblasts do not terminate biosynthesis and secretion of enamel proteins once the final layer has been deposited on the surface of the developing enamel. They continue to form and release new proteins during the maturation stage which intermix with older proteins laid down initially during the secretory stage of amelogenesis. Secretory activity for enamel proteins has been detected in ameloblasts up to at least the second ruffle-ended phase of maturation, at which point the enamel matrix is partially soluble in EDTA.

Ameloblasts↗
PubMed1987

Accelerated onset and delayed recovery of d-tubocurarine blockade with pancuronium in infants and children.

The effect of age on the onset and duration of action of a d-tubocurarine (DTC) neuromuscular blockade with and without pancuronium priming in children was examined. Sixty ASA physical status I or II patients in three age ranges (0-1 yr, 1-3 yr and 3-10 yr) were anaesthetized with thiopentone, halothane and nitrous oxide. Each patient received either a single paralyzing dose of DTC 0.4 mg.kg-1, or DTC 0.36 mg.kg-1 preceded three minutes earlier by pancuronium 0.007 mg.kg-1. Evoked force of contraction of the adductor pollicis was measured using train-of-four stimulation applied every 12 sec. Time to 90 per cent first twitch depression after a single dose of DTC increased with increasing age (r = 0.65, p less than 0.01), and was 1.6 min (SEM +/- 0.3) in the 0-1 yr group, 1.9 +/- 0.3 min (1-3 yr), and 5.2 +/- 1.2 min (3-10 yr). Time to ten per cent spontaneous recovery after single dose DTC was shorter in older individuals (r = 0.40, p less than 0.05), being 36.4 +/- 5.1 min in infants 0-1 yr, 30.6 +/- 4.6 min (1-3 yr), and 24.0 +/- 2.7 min (3-10 yr). Priming with pancuronium accelerated the onset significantly in all age groups with 90 per cent T1 depression occurring at 0.7 +/- 0.1 min (0-1 yr), 0.9 +/- 0.1 min (1-3 yr), and 2.1 +/- 0.6 min (3-10 yr). However, priming delayed recovery, especially in infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗