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Biomedical subjects

R D Miller

Publications and source records attributed to R D Miller.

At least 379 records · Page 21Linked to original sources

Early and late relative potencies of pancuronium and d-tubocurarine in man.

In ten patients anesthetized with halothane and nitrous oxide, d-tubocurarine or pancuronium was infused continuously for 80 minutes to produce a constant 90 per cent depression of twitch tension. For the first 30-minutes period, 8.2 +/- 0.32 and 1.09 +/- 0.06 (mean +/- SE) mg/m2 of d-tubocurarine or pancuronium, respectively, were required, and for the last 30-minutes period (50 to 80 minutes of infusion) 2.1 +/- 10.10 and 0.41 +/- 0.02 mg/m2 were required, giving potency ratios of 8.2/1.1, i.e., 7.4, and 2.1/0.41, i.e., 5.1. The difference in potency ratios in the first and last 30-minutes periods implies that potency values determined by single-injection techniques inadequately describe the relative requirements for sustained paralysis. The mean ratios between that amount of relaxant representing tissue uptake and that amount representing metabolism and renal excretion during the first 30 minutes were 3.06 +/- 0.28 for d-tubocurarine and 1.63 +/- 0.19 for pancuronium. The significantly higher ratio for d-tubocurarine implies that its tissue uptake relative to metabolism and renal excretion is greater than that for pancuronium. The higher ratio for d-tubocurarine may be partly explained by its greater binding to plasma and tissue proteins.

Adult↗

Antagonism of neuromuscular blockade.

Although acetylcholinesterase inhibitors are accepted antagonists of nondepolarizing neuromuscular blockade, many basic questions are still unanswered. What is the relationship between receptor occupancy and adequate ventilation? What are the effects of changes in acid-base balance and temperature? What are the mechanisms of the various antibiotic-induced neuromuscular blockades, and what antagonizes them? This review is an attempt to summarize the known factors infuencing relaxant blocks and to identify the unknown factors. The need for further studies is obvious.

Acid-Base Equilibrium↗

Clindamycin enhances a nondepolarizing neuromuscular blockade.

Neuromuscular blockades induced by clindamycin alone and with d-tubocurarine or pancuronium were examined in the in-vitro guinea pig lumbrical muscle-nerve preparation. Clindamycin, 80-240 mug/ml, initially increased twitch tension. With higher concentrations (180-240 mug/ml) twitch tension subsequently decreased. With 15 to 20 per cent depression of twitch tension by clindamycin, neostigmine (5-20 ng/ml) or calcium (81 mug/ml) slightly but not completely antagonized the blockade. Clindamycin, 40 mug/ml, a dose that did not depress twitch tension, potentiated d-tubocurarine- or pancuronium-induced neuromuscular bloackade. Plasma concentrations of clindamycin of 10-40 mug/ml were recommended for treating serious infections. The authors conclude that the administration of clindamycin may augment nondepolarizing blockade in man, and antagonism by neostigmine and calcium may be incomplete.

Adjuvants, Anesthesia↗

The occurrence of cell-associated enterotoxin B in Staphylococcus aureus.

Cell-associated enterotoxin B was detected in lysates of cells of Staphylococcus aureus S-6 and 4916 disrupted by sonication or lysostaphin treatment. As much as 67% of this total cell-associated toxin was surface-bound, located outside the cytoplasmic membrane, and was released during protoplasting of this organism by lysostaphin treatment in hypertonic medium. The remainder of the cell-associated toxin was termed cytoplasmic and was released during osmotic lysis of the protoplasts. Levels of cell-associated toxin as a function of the age of the cells showed a rapid increase in both surface-bound, cytoplasmic, and total cell-associated toxin levels during the period of active toxin synthesis (late exponential phase of growth). These cell-associated toxin levels then reached a peak as the culture entered stationary phase, at a time corresponding to a decrease in the rate of toxin synthesis, and decreased slowly thereafter.

Cell Membrane↗

Phagocytosis and cutaneous delayed hypersensitivity in patients with chronic obstructive pulmonary disease.

The objective of this study was to determine if the phagocytic and intracellular killing capacity of peripheral granulocytes or an expression of cellular-mediated immunity, delayed cutaneous reactivity, as measurements of native and acquired immunity, might be risk factors associated with chronic obstructive pulmonary disease (COPD). Over 100 patients with a value for their forced expiratory volume in one second (FEV1) less than or equal to 70 percent of normal were carefully matched with healthy participants having an FEV1 greater than or equal to 86 percent of normal, and together they served as the study group. Phagocytosis and intracellular killing were normal in patients with COPD; however, these patients demonstrated a significant impairment in the ability of their peripheral leukocytes to reduce nitroblue tetrazolium. The delayed-hypertensitivity response rate and the degree of reactivity were similar in the two groups, except for the patients with COPD having a significantly greater degree of reactivity to Monilia albicans extract ("canadin.") This finding is thought to be a consequence of reduced mucociliary clearance rather than a risk factor. The significance of decreased resting and stimulated cells' reduction of nitroblue tetrazolium in patients with COPD is not clear.

Aged↗

High performance liquid chromatography of natural products. I. Separation of cephalosporin C derivatives and cephalosporin antibiotics;isolation of cephalosporin C from fermentation broth.

Microbonded propylamine silica with a solvent system containing acetic acid, methanol, acetonitrile and water (2:4:7.5:86.5) is suitable for an efficient separation of mixtures containing several closely related cephem derivatives. The same system with preparative columns was used for the isolation of cephalosporin C directly from the filtered broth of C. acremonium fermentation.

Acremonium↗

Host factors in chronic obstructive pulmonary disease in an upper Midwest rural community. Design, case selection, and clinical characteristics in a matched-pair study.

A series of 111 index subjects with chronic obstructive pulmonary disease (COPD) who had forced expiratory volume in 1 second (FEV1) of 70% or less of that predicted were matched on the basis of age, sex, occupation, and smoking history with control subjects who had an FEV1 of 85% or more of that predicted. Index and control subjects with seasonal or reversible airway disease were excluded. Men outnumbered women by a ratio of 4.5 to 1. Thirty-five percent of the women and 2% of the men were nonsmokers (0 pack-years). There were three PiZ phenotypes in the index group (two nonsmokers) and none in the controls. PiMZ phenotypes in the index group outnumbered those in the controls by 8 to 5. Host factors that might be important in these closely matched pairs were sought by history, physical examination, and a large battery of laboratory tests. A standard respiratory questionnaire revealed the anticipated significantly higher frequency of cough, phlegm, noisy respiration, and all grades of dyspnea in index subjects. Previous lower respiratory tract infections also were more frequent in index subjects than in controls. There were no detectable differences between groups in the frequency of upper airway infections, nasal polyps, sinus surgery, or reported allergy to any substance. If the British Medical Research Council's definition of chronic bronchitis were applied to our study, about two-thirds of our index subjects and almost one-third of our controls would be considered to have chronic bronchitis. Pack-years of smoking were not significantly associated with the amount and duration of cough and expectoration in male or female index subjects or controls. Significant differences between index and control groups on physical examination included the audible forced expiratory flow time over the trachea, the estimated maximal midexpiratory flow, breath sounds, rales, and total excursion of the hemidiaphragms. An endocrine questionnaire and measurement of blood sex hormones did not give any clues as to the propensity of males to develop COPD. Women with airway obstruction similar to that of men had histories of significantly fewer pack-years than did the men, and there was a much larger proportion of women who never smoked. Further studies, specifically on genetic and immunologic characteristics, are under way to identify potential host factors.

Bronchitis↗

Neuromuscular effects of enflurane, alone and combined with d-Tubocurarine, pancuronium, and succinylcholine, in man.

The neuromuscular effects of d-tubocurarine (dTc), pacuronium, and succinylcholien (SCh) were studied in 37 unpremedicated adult surgical patients anesthetized with 1.25 MAC enflurance in oxygen. The relaxant doses that produced 50 per cent depression of twitch height (ED50) were 1.57, 0.29, and 4.9 mg/m2 for dTc, pancuronium, and SCh, respectively. These doses are approximately 3.1, 1.7, and 1.0 times less than the amount of dTc, pancuronium, and SCh required to produce 50 per cent depression of twitch height during halothane anesthesia but are the same as ED50 values during isoflurane anesthesia. In eight additional unpremedicated patients anesthesia was maintained at 0.71 MAC enflurane in oxygen (five patients) or 1.67 MAC enflurane in oxygen (three patients). Twitch depression following dTc, 1.5 mg/m2, was related directly to alveolar enflurane concentration. Ability to sustain tetanus decreased progressively with increasing tetanic frequencies and decreased with increasing alveolar enflurane concentrations. The authors concluded that smaller doses of dTc and pancuronium are needed for adequate relaxation during enflurane anesthesia than during equi-MAC halothane anesthesia, and that higher alveolar enflurane concentrations reduce the dose of dTc necessary to produce a given amount of paralysis. Also, neuromuscular effects of enflurane in combination with dTc or pancuronium are not significantly different from those seen suring equi-MAC isoflurane anesthesia.

Anesthesia, Inhalation↗

The effect of acid-base balance on neostigmine antagonism of d-tubocurarine-induced neuromuscular blockade.

d-Tubocurarine (dTc) was infused intravenously into 35 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch height of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean infusion rates that produced 90 per cent depression were not significantly altered by respiratory acid-base changes. Metabolic alkalosis decreased (32.5 per cent) and metabolic acidosis increased (27.7 per cent) the required infusion rate of dTc. When pH and Paco2 were maintained at 7.37 and 38 torr, respectively, the addition of a bolus of neostigmine, 10.5 mug/kg, intravenously, to the continuing infusion of dTc produced 50 per cent antagonism of the dTc-depressed twitch. Respiratory alkalosis and metabolic acidosis did not alter the dose of neostigmine needed to produce 50 per cent antagonism. However, during respiratory acidosis (pH 7.13, Paco2 66 torr) and metabolic alkalosis (pH 7.59, Paco2 36 torr) 20.0 and 18.0 mug/kg neostigmine, respectively, were needed to produce 50 per cent antagonism. Still larger doses of neostigmine (75 mug/kg) could not completely antagonize the block unless pH and Paco2 were returned to 7.30-7.50 and 35-45 torr, respectively. It is concluded that respiratory acidosis and metabolic alkalosis limit and oppose antagonism of dTc by neostigmine.

Acid-Base Equilibrium↗

Treatment of intercostal neuralgia with 10 per cent ammonium sulfate.

Intercostal nerves were injected with 10 per cent annomium sulfate in 41 patients (52 total sets of injections) for management of intercostal neuralgia from radical mastectomy (six blocks), thoracotomy (20 blocks), or unknown etiology (26 blocks). Five patients failed to return for follow-up evaluation and could not be located. Sixty per cent (28/47) of the treatments produced complete or nearly complete (excellent) relief of pain. Excellent pain relief persisted for more than 20 days after 22 treatments and for more than 90 days after seven treatments. Postblock neuritis never occurred. We conclude that intercostal nerve block with 10 per cent ammonium sulfate effectively relieves intercostal neuralgia and is not associated with postblock neuritis. We therefore believe that ammonium sulfate nerve blocks should be administered for treatment of intercostal neuralgia before phenol or alcohol nerve blocks or a surgical procedure.

Ammonium Sulfate↗

The effect of temperature on a d-tubocurarine neuromuscular blockade and its antagonism by neostigmine.

In 19 cats anesthetized with chloralose and urethrane, d-tubocurarine (d-TC) was continuously infused to produce constant 90% depression of twitch tension prior to injection of 5, 10 or 20 mug/kg of neostigmine. The required mean infusion rates of d-TC were 3.6 +/- 0.6, 5.1 +/- 0.3, 8.5 +/- 0.3 and 8.9 +/- 0.5 mug/kg/min at body and muscle temperatures of 28, 31, 37 and 41 degrees C, respectively. The doses of neostigmine needed for 50% antagonism of the d-TC-induced depression of twitch height were 8.7, 9.2, 10.5 and 12.0 mug/kg at 28, 31, 37 and 41 degrees, respectively. The time to peak effect and duration of action of 5 and 10 mug/kg of neostigmine were longer at 28 and 31 degrees C than at 37 and 41 degrees C. Although these times also were longer at 27 and 31 degrees C with the 20 mug/kg dose of neostigmine, they were not statistically different. We conclude that hypothermia augments a d-TC neuromuscular blockade. Hypothermia prolongs time-to-peak effect and duration of neostigmine but does not affect peak magnitude of antagonism of d-TC by neostigmine.

Animals↗