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Biomedical subjects

R D Miller

Publications and source records attributed to R D Miller.

At least 343 records · Page 19Linked to original sources
PubMed1979

Temporal arteritis and polymyalgia rheumatica: two aspects of one disease.

Temporal (cranial, giant cell) arteritis and polymyalgia rheumatica are probably different expressions of the same inflammatory disease. The disease occurs mainly in the elderly and is characterized in the early stage by vague, nonspecific symptoms. Tenderness of the temporal arteries is diagnostic but rarely is present early. Unfortunagely, loss of vision usually occurs before the diagnosis is made. A high index of suspicion and frequent testing of the ESR in elderly patients with vague complaints may lead to earlier diagnosis and appropriate therapy and thus may prevent blindness and even death.

Blindness↗
PubMed1979

4-Aminopyridine potentiates neostigmine and pyridostigmine in man.

To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism, while 0.5 mg/kg produced a mean 24 +/- 6 per cent (peak) antagonism. The dose that produced 50 per cent antagonism (ED50) of neostigmine alone was 22 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 micrograms/kg. The ED50 of pyridostigmine alone was 110 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 micrograms/kg. 4-Aminopyridine prolonged the onset times of both neostigmine and pyridostigmine, but prolonged the duration of action of neostigmine only. At a given level of antagonism of pancuronium, adding 4-aminopyridine 0.35 mg/kg, to neostigmine and to pyridostigmine decreased the amounts of atropine needed to prevent a change in heart rate by 68 and 70 per cent, respectively. The authors conclude that 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Also, less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.

Adult↗
PubMed1979

Plasma concentrations of pancuronium and neuromuscular blockade after injection into the isolated arm, bolus injection, and continuous infusion.

To establish whether the plasma concentration of pancuronium reflects magnitude of neuromuscular blockade, the authors determined times of recovery from neuromuscular blockade and associated plasma concentrations following equipotent doses of pancuronium using three methods of pancuronium administration: the isolated-arm technique in conscious volunteers (n = 4), and the bolus intravenous injection (n = 7) and continuous-infusion methods (n = 3) in anesthetized patients. Although maximum depressions of twitch tension were similar (85 +/- 11,91 +/- 6, and 92 +/- 4 per cent, respectively) with the three techniques, times to recovery from neuromuscular blockade differed significantly, being 10 +/- 2 min with the isolated-arm technique, 23 +/- 7 min with the bolus-injection technique, and 46 +/- 5 min with the continuous-infusion method. The plasma concentration of pancuronium necessary for neuromuscular blockade was least with the isolated-arm technique and greatest with continuous infusion. At 25 and 75 per cent recovery, mean plasma concentrations were 0.07 +/- 0.01 and 0.04 +/- 0.01 microgram/ml in the isolated arm; 0.13 +/- 0.04 and 0.09 +/- 0.02 microgram/ml after bolus injection, and 0.20 +/- 0.04 and 0.11 microgram/ml during continuous infusion, respectively. It is concluded that the relationship between plasma concentration of pancuronium and magnitude of neuromuscular blockade depends on the method of pancuronium administration.

Humans↗
PubMed1979

Effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium in the cat.

To investigate the effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium, 120 microgram/kg i.v., cats were anesthetized with either pentobarbital (N = 4), ketamine (N = 4), enflurane (N = 5), or halothane (N = 5). A longer onset time and duration of neuromuscular blockade occurred during enflurane and halothane anesthesia. The apparent elimination half-life was longer and the total voluem of distribution at steady state larger during halothane anesthesia. The plasma concentration of pancuronium required for neuromuscular blockades was less during enflurane than during the other three anesthetics. We conclude that inhalation anesthetics may prolong a neuromuscular blockade by altering both the pharmacokinetics and pharmacodynamics of pancuronium.

Adjuvants, Anesthesia↗
PubMed1979

Growth of Legionnaires disease bacterium (Legionella pneumophila) in chemically defined medium.

A chemically defined medium containing 21 amino acids and inorganic salts was developed which supported the growth of four isolates of Legionnaires disease bacterium (Legionella pneumophila). Growth in liquid defined medium at 37 degrees C with shaking approximated the generation time and growth kinetics observed for growth in complex media. After a 3-h lag, the culture grew exponentially with a generation time of 6 h and reached a maximum optical density of 230 Klett units (170 Klett units corrected for pigment). A soluble brown pigment was first observed as the culture entered late exponential to early stationary phase of growth. Morphologically, L. pneumophila grew in the liquid defined medium with extensive filamentation and numerous intracellular lipid granuoles. L-Serine, L-methionine, and L-cysteine were required for optimum growth. The latter amino acid could be replaced by L-cystine or reduced glutathione but not by D-cysteine, thiomalate, thioglycollate, or 2-mercaptoethanol. Ferric iron was needed for maximum growth, but supplemental iron was not an essential growth requirement. Carbohydrates (i.e., glucose) or organic acids did not stimulate growth. In fact, pyruvate, acetate, and citrate all gave varying degrees of inhibition (69, 37, and 0% of control growth, respectively).

Amino Acids↗
PubMed1979

Immunoglobulin concentrations in serum and nasal secretions in chronic obstructive pulmonary disease. A matched-pair study.

Immunoglobulin concentrations were determined in the sera and nasal washes of 111 patients with chronic obstructive pulmonary disease who were 45 to 60 years of age and in 111 control subjects matched with the patients for age, sex, occupation, and smoking history who demonstrated normal 1-sec forced expiratory volume. Serum IgA, IgM, IgG, nad IgE were not significantly different in the 2 groups. Serum IgD was significantly higher in subjects with chronic obstructive pulmonary disease. Nasal wash IgD and IgM, expressed as percentages of total protein, were higher in index cases, but nasal wash IgA and IgG were comparable in both groups. The finding of relatively high concentrations of IgA, expressed as fractions of total protein, in respiratory secretions compared to serum is consistent with earlier findings that IgA is actively secreted from the respiratory epithelium and is not deficient locally in subjects with chronic obstructive pulmonary disease. In contrast, IgM and IgG expressed as proportions of total protein were consistently higher in sera than secretions. The IgE in nasal secretions was detected so seldom in this study that too few matched pairs were available for statistical analysis. The higher concentration of IgD in the serum and nasal secretions of patients with chronic obstructive pulmonary disease compared with their matched pairs and the associated higher frequency of low IgD in control subjects suggests that low IgD may be protective against the development of chronic obstructive pulmonary disease. Further studies on the biologic role of IgD may provide better understanding of these findings.

Humans↗
PubMed1978

Acid-base balance and neostigmine antagonism of pancuronium neuromuscular blockade.

In 40 cases anesthetized with chloralose and urethane, pancuronium was infused i.v. at a constant rate to produce and maintain 90% depression twitch tension of the anterior tibialis muscle following supramaximal stimulation of the peroneal nerve. Neither respiratory alkalosis nor metabolic acidosis influenced the infusion rate required to produce 90% depression of twitch tension or antagonism of this depression yb neotigmine. Respiratory acidosis (pH 7.15; PaCO2 10 kPa) did not alter the required infusion rate but did prevent complete antagonism by neostigmine. Metabolic alkalosis (pH 7.65; PaCO2 4.8 kPa) reduced both the required infusion rate and prevented complete restoration of twitch tension by neostigmine. The duration of neostigmine antagonism was shortened by metabolic alkalosis. We conclude that respiratory acidosis and metabolic alkalosis prevent antagonism of pancuronium by neostigmine.

Acid-Base Equilibrium↗
PubMed1978

Diuretic-induced hypokalaemia, pancuronium neuromuscular blockade and its antagonism by neostigmine.

The effect of hypokalaemia on a neuromuscular blockade induced by pancuronium and its antagonism by neostigmine was studied in the cat anterior tibialis-peroneal nerve preparation using the constant infusion of pancuronium technique. Hypokalaemia was induced by chronic administration of chlorothiazide. The infusion rate of pancuronium required to maintain a 90% depression of twitch tension was reduced from 0.72 +/- 0.06 microgram kg-1 min-1 in the cats with a normal serum concentration of potassium (K+ = 4.4 +/- 0.2 mmol litre-1; n = 7) to 0.41 +/- 0.07 microgram kg-1 min-1 in the hypokalaemic cats (K+ = 2.3 +/- 0.1 mmol litre-1; n = 8). The dose of neostigmine necessary for 50% antagonism of the pancuronium-induced depression of twitch tension (ED50) was 10.0 microgram kg-1 in the cats with a normal potassium concentration and 18.5 microgram kg-1 in hypokalaemic cats. We conclude that hypokalaemia decreases the dose of pancuronium required for neuromuscular blockade and increased the dose of neotigmine required for antagonism of the block.

Animals↗
PubMed1978

Pharmacokinetics and pharmacodynamics of d-tubocurarine during hypothermia in the cat.

To determine the effects of hypothermia on the pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc), serum, biliary, and urinary concentrations were determined and twitch tension monitored following intravenous administration of dTc, 0.7 mg/kg, at 39 (n = 5), 34 (n = 5), and 28 C (n = 6) in cats anesthetized with chloralose and urethane. Time from injection of dTc to maximum neuromuscular blockade was prolonged by hypothermia (28 C). Similarly, moderate (28 C) but not mild (34 C) hypothermia delayed recovery from paralysis. The serum half-life was prolonged 76% and the serum clearance rate decreased 60% by hypothermia (28 C). The combined biliary and urinary elimination of dTc was decreased 47% at 28 C compared with 34 and 39 C. The serum concentration of dTc necessary for neuromuscular blockade was less at 39 C (ED50 0.87 microgram/ml) than at 34 or 28 C (ED50 1.13 microgram/ml). It is concluded that, in vivo, hypothermia antagonizes a dTc-induced neuromuscular blockade but decreases the elimination of dTc. At 28 C the net effect is a prolongation of neuromuscular blockade.

Animals↗
PubMed1978

Potentiation of neostigmine and pyridostigmine by 4-aminopyridine in the rat.

The interaction between 4-aminopyridine and neostigmine or pyridostigmine was studied in vivo in the rat sciatic nerve-anterior tibialis preparation using the constant infusion of pancuronium technique. The ED50 (dose of drug which produced a 50% antagonism) of neostigmine, pyridostigmine and 4-aminopyridine were 18, 49 and 440 microgram kg(-1) respectively. The addition of 100 microgram kg(-1) of 4-aminopyridine, which produced no antagonism by itself, decreased the neostigmine ED50 to 7.4 microgram kg(-1). The addition of 200 microgram kg(-1) of 4-aminopyridine, which produced a 30% antagonism by itself, decreased the ED50 of pyridostigmine to 11 microgram kg(-1). We conclude that both neostigmine and pyridostigmine interact with 4-aminopyrine synergistically.

Aminopyridines↗
PubMed1978

Binding of cholesterol by Neisseria gonorrhoeae.

The binding of [1,2-3H]cholesterol to Neisseria gonorrhoeae CS-7, Pseudomonas aeruginosa, and Salmonella typhimurium (smooth and rough strains) was investigated. The kinetics of cholesterol binding to N. gonorrhoeae CS-7 demonstrated that binding occurred slowly with maximum binding by 10 h. Under optimum conditions, a large percentage (65%) of the added cholesterol was associated with the cells. Chemical fractionation revealed that ca. 98% of the labeled cholesterol was associated with the cell membrane(s). The bound cholesterol was not esterified and was associated primarily with the cytoplasmic membrane. Intact gonococci bound 4 to 30 times more cholesterol than the deep rough mutant S. typhimurium TA1535, the wild-type S. typhimurium DB-21, and P. aeruginosa. In contrast, isolated cell membranes from all organisms rapidly bound cholesterol to the same extent. Therefore, the outer membrane can function as a permeability barrier to cholesterol. Cholesterol binding to both whole cells and isolated cell membranes was influenced by the incubation temperature. The rate of cholesterol binding by whole cells of N. gonorrhoeae decreased markedly at lower temperatures, with almost complete cessation of binding at 0 degrees C. A similar temperature effect on the binding of cholesterol to isolated membranes was not observed. Thus, the effect of temperature on the binding of cholesterol to whole cells was an effect not on the actual binding process but rather on the ability of the cholesterol molecule to penetrate the lipid domain of the gonococcal outer membrane.

Cell Membrane↗
PubMed1978

Pulmonary function studies in healthy Pakistani adults.

Predicted normal spirometric values have been shown to have significant geographical and ethnic variation. These variations are of epidemiological significance in determining the prevalence of disease and of clinical importance in measuring the effects on pulmonary function of various diseases. A total of 599 men were chosen from employees of a package manufacturer, a general hospital in Lahore, and a village in northern Pakistan; 94 students and staff of a women's college in Lahore were also studied. The forced vital capacity (FVC) was recorded from three satisfactory efforts, and the FVC, one second forced expiratory volume (FEV1), and maximal midexpiratory flow (MMF, or FEF25-75%) were calculated from the best FVC effort. The FVC and FEV1 in men were found to be similar to those of a group of emigrant Pakistanis and a north-western Indian population (Delhi) but higher than populations in south and eastern India. Pakistani women had values similar to those of women in northern India. None of the women smoked and, among Pakistani men, the smokers (285) averaged 6.7 pack years. While the FVC and FEV1 values did not differ between smokers and non-smokers, there was a significant difference in MMF (FEF25-75%) in the two groups. This latter finding corroborates studies on North American populations in which smokers generally have had a higher lifelong cigarette consumption. This confirms the MMF (FEF25-75%) to be a more sensitive test of subtle, asymptomatic changes in pulmonary function than the more widely used FVC and FEV1.

Adult↗