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Biomedical subjects

R D Miller

Publications and source records attributed to R D Miller.

At least 289 records · Page 16Linked to original sources
PubMed1982

Antagonism of org NC 45 (vecuronium) and pancuronium neuromuscular blockade by neostigmine.

The antagonism, by neostigmine, of neuromuscular blockade produced by either Org NC 45 or pancuronium was studied in 29 anaesthetized patients during a continuous infusion of the myoneural blocker. The ED50 of neostigmine (dose which produced a 50% antagonism) when antagonizing Org NC 45 and pancuronium was 0.011 mg kg-1 and 0.010 mg kg-1 respectively. The dose-response relationships for the antagonism of Org NC 45 and pancuronium neuromuscular blockades were not significantly different. The duration of the effect of neostigmine was not different when antagonizing an Org NC 45- or pancuronium-induced blockade. We concluded that Org NC 45 and pancuronium are effectively and equally (independent of pharmacokinetics) antagonized by neostigmine in man.

Adult↗
PubMed1982

Decreasing enflurane concentrations and d-tubocurarine neuromuscular blockade.

To study the effect of decreasing the concentration of enflurane on a combined enflurane-d-tubocurarine (dTC) neuromuscular blockade, six ASA class I or II patients were studied using a continuous infusion of dTC and a sequence of decreasing end-tidal concentrations of enflurane. A constant infusion of dTC and a 2.2 per cent end-tidal concentration of enflurane decreased twitch tension to 8 per cent of control. Maintaining this same infusion rate of dTC, but decreasing the end-tidal concentration of enflurane to 1.35 and 0.5 per cent, increased the twitch tension to 57 and 91 per cent of control, respectively. The authors conclude that the enflurane contribution to muscle relaxation dissipates in a dose-dependent manner as the end-tidal concentration of enflurane is reduced. This factor may provide additional safety for patients because the anesthetic produces a component of relaxation that is readily reversible with time without the use of acetylcholinesterase inhibitors.

Adult↗
PubMed1982

Pharmacokinetics and pharmacodynamics of d-tubocurarine in infants, children, and adults.

The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 months, n = 7), infants (2-12 months, n = 7), children (1-12 years, n = 9), and adults (12-30 years, n = 8) during 70% nitrous oxide, 0.58 MAC halothane anesthesia. dTc was administered by infusion, while blood for determination of plasma dTc concentrations was obtained, and the EMG of the adductor pollicis recorded. The plasma dTc concentration at which 50% depression of EMG twitch height occurs (Cpss(50)) was 0.18 +/- 0.09 micrograms/ml in neonates, and 0.27 +/- 0.06 micrograms/ml in infants, both significantly lower than the values of 0.42 +/- 0.14 and 0.53 +/- 0.14 micrograms/ml for children and adults, respectively. The steady-state distribution volume (Vdss) was 0.74 +/- 0.33 l/kg in neonates, significantly greater than the values of 0.52 +/- 0.22, 0.41 +/- 0.12, and 0.30 +/- 0.10 l/kg in infants, children, and adults, respectively. The elimination half-life (t beta 1/2) was 174 +/- 60 min in neonates, significantly longer than the values of 90 +/- 23 and 89 +/- 18 min in children and adults, respectively. Plasma clearance did not differ with age. We also determined D50, the product of Vdss and Cpss(50). D50, the quantity of drug present at steady-state to produce 50% paralysis, did not differ between groups. The authors conclude that during comparable nitrous oxide-halothane anesthesia, neonates and infants have an increased sensitivity to dTc, as determined by CPss(50). However, because of the larger Vdss in younger patients, dose size should not differ with age. In addition, because of the longer t beta 1/2 in neonates, second and subsequent doses should be required at less frequent intervals.

Adolescent↗
PubMed1982

Potency determination for vecuronium (ORG NC45): comparison of cumulative and single-dose techniques.

To compare two methods of estimating the potency of neuromuscular relaxants of medium duration, the authors determined the potency of vecuronium (ORG NC45) using cumulative dose-response (CDR) techniques, and compared these data with published values from our group obtained using the single bolus technique. During 60% N2O-halothane anesthesia, patients received 10 micrograms/kg vecuronium; additional incremental doses of vecuronium, 5 micrograms/kg, were given when no change occurred in the height of three successive twitches. Using these dose-response data, the authors determined least-squares regression lines and ED20, ED50, and ED80. These results were compared to values obtained by the single bolus technique under comparable conditions. The CDR and single bolus technique yielded ED50 values of 19.9 and 15.0 micrograms/kg, respectively. All potency estimates by CDR were larger than those obtained by the single bolus dose technique. It was concluded that, for vecuronium, a medium duration neuromuscular relaxant, CDR yields potency estimates which are larger than those obtained by the traditional single bolus dose technique. Because the single bolus dose technique is the accepted method for construction of dose-response curves, the authors recommended that CDR not be used for potency determination of muscle relaxants of medium and short duration such as vecuronium.

Adult↗
PubMed1982

Effects of furosemide on the neuromuscular junction.

These studies investigated the direct effects of furosemide on neuromuscular transmission using the in vitro rat phrenic nerve diaphragm and the in vivo at soleus nerve muscle preparations. Furosemide (10(-6)-10(-4)m) reduced the concentration of d-tubocurarine required to achieve 50% twitch tension depression in the indirectly stimulated rat diaphragm. Intraarterial injection of furosemide had a biphasic effect on the cat neuromuscular junction. At low doses (0.1-10.0 micrograms/kg) the drug had a depressant effect, reduced the force of muscle contraction, prevented nerve and muscle responses to NaF and dibutryl cyclic AMP, and intensified the neuromuscular blockade produced by d-tubocurarine and succinylcholine. In contrast, in higher doses (1-4 mg/kg) furosemide produced stimulus-bound repetitive neural activity, initiated neural activity, increased the force of muscle contraction, enhanced nerve and muscle responses to NaF and dibutyrl cyclic AMP, and antagonized d-tubocurarine and succinylcholine blockades. Furosemide had no effect on denervated preparations. High doses of furosemide inhibit non-competitively both the high- and low-affinity forms of the enzyme cyclic AMP phosphodiesterase in both soluble and particulate fractions of cat sciatic nerve. Thus, furosemide has direct effects on neuromuscular transmission, but the direction of these effects is dose-dependent.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Characterization of the immune response in subcutaneous chambers of guinea pigs immunized with a ribosomal preparation from Neisseria gonorrhoeae.

Immunization of guinea pigs with ribosomal preparations has been previously shown to be protective against chamber infection with Neisseria gonorrhoeae, and this protection could be correlated with the presence of serum bactericidal antibody. Analysis of the chamber fluids from ribosome-immunized and nonimmunized guinea pigs has demonstrated that the chamber fluid may accurately reflect serum antibody levels and proteins. At least one major population of antiribosomal antibodies is present in both immune serum and chamber fluid as revealed by lines of identity between these components. Antibody- and complement-mediated bactericidal assays revealed that matched chamber fluids and sera from immune animals had comparable bactericidal titers. These results suggest that the antibody-complement-mediated bactericidal activity plays a major role in the protection against N. gonorrhoeae infection. Protection could not be explained on the basis of the cellular components of the inflammatory response since both immune and nonimmune chambers had comparable increases in polymorphonuclear neutrophils, monocytes, and lymphocytes after challenge.

Animals↗
PubMed1982

Interaction between plant agglutinins and Legionella species.

Serogroups of Legionella pneumophila exhibited differential reactivities with plant agglutinin. Agglutination patterns were modified by growing the organisms in different media. The passage of four strains through guinea pigs did not result in altered reactivities with lectins or with plant agglutinins.

Alkalies↗
PubMed1982

Genetic control of excision of Saccharomyces cerevisiae interstrand DNA cross-links induced by psoralen plus near-UV light.

Excision of interstrand DNA cross-links induced by 4,5',8-trimethyl psoralen plus 360-nm light was examined in wild type (RAD+) and various radiation-sensitive (rad) mutants of Saccharomyces cerevisiae known to be defective in the excision of UV light-induced pyrimidine dimers. Alkaline sucrose sedimentation of DNA after incubation of psoralen-plus-light-treated cells indicated little or no nicking of cross-linked DNA in rad1-2, rad2-5, rad3-2, rad4-4, rad10-2, and mms19-1 mutants. In the rad14-2 mutant, substantial nicking was observed but to a much lesser extent than in the RAD+ strains, whereas the rad16-1 mutant was as proficient in nicking as the RAD+ strain. Removal of cross-links was also examined in RAD+, rad3-2, and rad14-2 strains by determining the sensitivity of alkali-denatured and -neutralized DNA to hydrolysis by S1 nuclease. No cross-link removal was observed in the rad3-2 mutants, and the rad14-2 mutant was much less efficient than the RAD+ strain in removing cross-links.

DNA Repair↗
PubMed1982

Growth of Legionella pneumophila in defined media: requirement for magnesium and potassium.

The inorganic ions magnesium and potassium were required for optimal growth of Legionella pneumophila in a chemically defined medium composed of amino acids and inorganic salts. Optimum growth was obtained at concentrations of approximately 20 micrograms/mL (80 microM) MgSO4 X 7H2O and 150 micrograms/mL (2 mM) KCl. Comparable results were obtained with all six serogroups of L. pneumophila as well as with both laboratory-adapted and animal-passed strains.

Culture Media↗
PubMed1982

Serum IgD in subjects with and without chronic obstructive pulmonary disease: a previous finding restudied.

A previous study of matched pairs of subjects with and without COPD showed higher geometric mean values of serum IgD among the affected subjects. In an attempt to replicate this finding in another sample a cooperative study was undertaken to measure IgD in subjects from an epidemiologic study of airway obstructive disease from a different geographic region. The relationship between serum IgD (Ine scale) and % FEV1, was identical in the 2 samples. The lack of statistical significance when analyzing the Arizona sample in a matched pair fashion is attributed to an underrepresentation of subjects with very low % FEV1, and smaller sample size.

Adult↗
PubMed1982

Renal and biliary elimination of vecuronium (ORG NC 45) and pancuronium in rats.

The urinary excretion of ORG NC 45 (Vecuronium) and of pancuronium was studied in unanesthetized rats and the biliary excretion was studied in anesthetized rats. Urine and bile were analyzed for unchanged drug by a new and specific mass spectrometric assay. Pancuronium was eliminated primarily in the urine (85% +/- 6% of the dose in 12 hours), but little ORG NC 45 appeared in the urine (3.5% +/- 1.1% in 12 hours). Biliary excretion accounted for 46% +/- 4% of the ORG NC 45 dose in 7 hours, but only 7.5% +/- 5.3% of an injected dose of pancuronium appeared in the bile. Thus, it appears that ORG NC 45 (a monoquaternary ammonium compound) has a higher biliary clearance than pancuronium (a bisquaternary ammonium compound). The different biodisposition of these two compounds may be due to the greater lipophilicity and concomitant enhanced permeability into the hepatocyte of ORG NC 45. We conclude that in the rat elimination of pancuronium is primarily via the kidney whereas elimination of ORG NC 45 is dependent on nonrenal mechanisms.

Animals↗
PubMed1982

Prognosis, management and outcome of obstructive renal disease in pregnancy.

The diagnosis and management of obstructive lesions of the urinary tract in pregnancy are hindered by lack of criteria for performing intravenous pyelography (IVP). The majority of obstructive lesions are caused by the gravid uterus; however, an important treatable cause is urinary tract calculi. In order to establish valid criteria for performing IVP in pregnancy, the intravenous pyelograms from 11 pregnant patients with urinary tract symptoms over a six-year period were evaluated. The clinical indications for urography, management of patients with urinary tract obstruction and the pregnancy outcome were studied and compared to those cases reported in the literature.

Adult↗
PubMed1982

Edrophonium: duration of action and atropine requirement in humans during halothane anesthesia.

Edrophonium's onset and duration of antagonism (n = 26) and atropine requirement (n = 24) were determined under conditions of d-tubocurarine (dTc) neuromuscular blockade and halothane, nitrous oxide anesthesia. Results are compared with previous work in our laboratory on neostigmine and pyridostigmine under similar conditions. dTc was administered by continuous infusion to maintain a 90% depression of muscle twitch tension. Edrophonium (0.03-1.0 mg/kg) was injected as an iv bolus in combination with atropine (0.5 mg). dTc infusion was continued until a stable 90% depression of muscle twitch tension was reestablished. Time-to-peak effect (onset of action), duration, and magnitude of antagonism were recorded. The atropine requirement was determined during spontaneous recovery from dTc (0.3 mg/kg) and stable halothane, nitrous oxide anesthesia. Edrophonium (0.5 mg/kg) was mixed with 7, 15, or 30 micrograms/kg of atropine and compared to neostigmine (0.043 mg/kg) and atropine (15 micrograms/kg). Blood pressure, heart rate, and rhythm were recorded for 60 min following edrophonium administration. The time-to-peak antagonism for edrophonium (0.8-2.0 min) was far more rapid than neostigmine (7-11 min) or pyridostigmine (12-16 min). The ED50 for edrophonium was 0.125 mg/kg, however, the dose-response curve was not parallel to those for neostigmine or pyridostigmine. In equiantagonistic doses, the duration of antagonism by edrophonium (66 min) did not differ from neostigmine (76 min), but was shorter than pyridostigmine. Edrophonium required one-half the amount of atropine as did neostigmine to prevent bradycardia. The authors concluded that edrophonium has a more rapid onset than neostigmine and an equivalent duration of antagonism, and requires less atropine to prevent bradycardia.

Anesthesia, General↗