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D L Fung

Publications and source records attributed to D L Fung.

At least 19 recordsLinked to original sources
PubMed1995

Predicting cardiac autonomic neuropathy in type I (insulin-dependent) diabetes mellitus.

A total of 24 subjects with type I insulin-dependent diabetes mellitus were studied. Cardiac parasympathetic function was measured by supine heart rate variability (HRV) in the respiratory frequency 0.10-0.50 Hz and the sympathetic index was measured as the ratio of HRV between 0.055 and 0.098 Hz to that between 0.004 and 0.5 Hz. Factors assessing diabetic control and complications, and factors unrelated to diabetes but possibly influencing HRV, were recorded. Association with depressed HRV was assessed with correlation, and prediction of depressed HRV was determined with multiple regression. Factors associated with depressed HRV but not independently predictive were renal dysfunction and elevated thyroid stimulating hormone. Elevated glycosylated haemoglobin was not significantly correlated with depressed HRV. Four factors (presence of diabetic retinopathy, male gender, duration of diabetes and increasing age) were significant in the regression and sufficed to predict 81% of the sample variance. The relative weights (beta) were -0.65, 0.40, -0.40 and 0.26, respectively. Supine sympathetic index was not sufficient to demonstrate sympathetic dysfunction. It is proposed that the regression model may be used to identify patients likely to have cardiac parasympathetic autonomic dysfunction.

Adult↗
PubMed1995

The changing pharmacodynamics of metocurine identify the onset and offset of canine gastrocnemius disuse atrophy.

BACKGROUND: Immobilization of skeletal muscle results in disuse atrophy and resistance to nondepolarizing muscle relaxants. We studied the pharmacodynamics of metocurine (MTC) to identify the development and recovery of disuse-related resistance to MTC. METHODS: Nineteen dogs underwent cast immobilization of a hind limb for as long as 3 weeks. Before, during, and after casting, dogs were intermittently anesthetized with thiamylal-N2O-fentanyl. The blood concentration of MTC and the corresponding degree of paralysis after a brief infusion were recorded and were used to characterize the pharmacokinetics and pharmacodynamics of MTC. RESULTS: Pharmacodynamic study of the response to MTC demonstrated resistance by the 4th day of casting. The effect-site concentration associated with 50% paralysis of twitch increased after 3 weeks from approximately 250 to 750 ng/ml. After cast removal, resistance persisted for 2 more weeks. Six weeks after cast removal, the effect-site concentration associated with 50% paralysis of twitch was normal in every dog. CONCLUSIONS: Within the context of this study of immobilization disuse atrophy, pharmacokinetic and pharmacodynamic characterization of antagonist responses can be used to infer muscle disuse-related changes in acetylcholine receptors.

Acetylcholine↗
PubMed1995

Allometry of pharmacokinetics and pharmacodynamics of the muscle relaxant metocurine in mammals.

We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmacokinetics, which were affected by physiological time (Mb0.25). Pharmacodynamics were size independent, except for the value for effect compartment concentration associated with 50% twitch paralysis (IC50). Data from individual species had a bimodal distribution that was significant: pigs and sheep were more sensitive than other large species, and their IC50 appeared size independent. IC50 was size dependent in more active species (horse, dog, cat, rat). Although the mechanism is unknown, we speculate that this trend might relate to receptor density within the end plate. Thus pharmacokinetics changed in proportion to physiological time, and pharmacodynamics were in part size independent.

Anesthesia, General↗
PubMed1992

Determination of sensitivity to metocurine in exercised horses.

On the basis of results in dogs, conditioning exercise may increase sensitivity to nondepolarizing muscle relaxants. Five Thoroughbreds were exercised/conditioned 3 times weekly on a treadmill for 8 months. Increasing maximal rate of O2 consumption verified that the horses were responding to exercise conditioning. Six nonexercised Thoroughbreds served as the control group. Studies were done with horses under general anesthesia by use of halothane during partial paralysis by a brief constant-rate infusion with the muscle relaxant, metocurine iodide. Quantification of degree of paralysis of the hoof twitch (eg, digital extensor) occurred with simultaneous quantification of blood values of metocurine. Pharmacokinetic and pharmacodynamic analyses of the data were done by a nonlinear regression program, using the Hill equation. There were no differences in findings between exercised and nonexercised horses. The mean blood concentration for the 50% paralyzing dose of metocurine was 0.44 +/- 0.11 (SD) microgram/ml in exercised horses, and 0.58 +/- 0.22 microgram/ml in nonexercised horses. Despite evidence for a response to conditioning, a significant change in the sensitivity of the neuromuscular junction to metocurine was not found.

Animals↗
PubMed1991

The onset of disuse-related potassium efflux to succinylcholine.

Disuse atrophy of skeletal muscle produces resistance to nondepolarizing relaxants and increased potassium efflux after the administration of succinylcholine. These changes appear to be due to development of perijunctional and/or extrajunctional receptors (up-regulation). In this study, the authors searched for the earliest detectable appearance of increased potassium efflux in beagles in whom disuse atrophy was simulated. Seven beagles underwent unilateral cast immobilization of a hind limb. Between 4 and 42 days, they periodically received succinylcholine 0.25 mg/kg while anesthetized with thiamylal and nitrous oxide. Sequential bilateral femoral venous samples showed that the casted limb did not manifest potassium release greater than the upper limit of normal (1 mEq/l) until cast immobilization periods of 14 days or longer. When this occurred, the increase in the potassium concentration in the femoral venous blood of the casted limb exceeded that from the noncasted limb by at least 0.7 mEq/l (P less than 0.01). The range for the onset of this response after casting was 14-42 days, the mean 27.2 days, and the standard deviation 9.8 days. These findings imply that up-regulation of skeletal muscle receptors, associated with exaggerated potassium efflux after administration of succinylcholine, is dependent on progressive development of extrajunctional receptors over surface membrane areas beyond the endplate.

Animals↗
PubMed1984

The use of propranolol in rapid sequence anaesthetic induction: optimal time interval for pretreatment.

Forty patients ASA physical status I-III were selected and divided into four groups. Group I, Control, received saline pretreatment five minutes prior to rapid sequence induction and intubation, while Groups II, III and IV received propranolol 0.01 mg X kg-1 IV two, five or eight minutes prior to induction and intubation. Measurements of heart rate (HR), arterial blood pressure (ABP) were recorded as baseline values and at one, two, five, eight and 20 minutes, and simultaneous venous samples were withdrawn for propranolol levels. Calculated rate pressure product (RPP) showed best haemodynamic control in Group III. Serum propranolol levels were under 5 ng X ml-1 in Group III and undetectable in Group IV. Our data show that the optimal time interval between IV propranolol administration and intubation was five minutes.

Adult↗
PubMed1983

Blood pressure response to phenylephrine infusion in halothane-anesthetized dogs given acetylpromazine maleate.

To quantitate acetylpromazine-induced alpha-adrenergic receptor blockade, phenylephrine was infused into dogs. The amount of phenylephrine necessary to increase the mean arterial blood pressure (MAP) 50% above base line, with or without the prior administration of acetylpromazine, served to quantify the degree of acetylpromazine-induced alpha-adrenergic receptor blockade. Seven dogs were anesthetized with thiopental, maintained on halothane in oxygen, and mechanically ventilated. All infusions were made through a catheter in the cephalic vein. Continuous recordings were made of MAP and a lead II ECG. After induction of anesthesia, instrumentation, and stabilization of heart rate, MAP, and ventilation, 6 group I dogs were infused with phenylephrine until a 50% increase in MAP was recorded (phenylephrine control). On subsequent research days, each dog was anesthetized, instrumented as described, and given (IV) 1 of 3 dosages of acetylpromazine in the following order--0.05, 0.125, and 0.25 mg/kg. The dose of phenylephrine necessary to increase MAP 50% in the presence of acetylpromazine was recorded. Five group II dogs were studied as in group I, but each dog was given (IM) atropine (0.04 mg/kg) before anesthetization. Two dosages of acetylpromazine were studied in the following order--0.05 and 0.25 mg/kg. Group I dogs, when compared with their phenylephrine controls, were given significantly more phenylephrine to raise MAP 50% at each dose of acetylpromazine studied. The same trend was observed in group II dogs, but at smaller doses of phenylephrine, probably as a result of the positive chronotropic effect of atropine on the heart.

Acepromazine↗
PubMed1982

Shock due to protamine hypersensitivity.

A 56-year-old man developed shock and skin flush minutes after the slow administration of 25 mg of protamine sulfate. Prior protamine exposure from treatment of his diabetes with isophane insulin (NPH insulin) was believed to have sensitized this patient to protamine. A review of three other cases of reaction to low doses of protamine revealed that in each, the patient had previously been exposed to protamine. If heparin is used in a patient with a history of treatment of diabetes with isophane insulin, the heparin should be allowed to spontaneously reverse, without pharmacological assistance if possible. If protamine must be used, the patient should be pretreated with glucocorticoid and vasopressors should be immediately available.

Diabetes Mellitus↗
PubMed1980

A comparison of alphaprodine and meperidine pharmacokinetics.

We have developed a gas-liquid chromatographic analysis for measuring plasma alphaprodine. The analysis is sufficiently sensitive for studying therapeutic-dose pharmacokinetics in man. Single intravenous bolus injections of either alphaprodine or meperidine were given to volunteer subjects. Plasma concentration data were fitted to a biexpoential equation and pharmacokinetic parameters were calculated. Consistent with alphaprodine's shorter clinical duration compared to meperidine, we found that plasma levels of alphaprodine decline at a more rapid rate. Plasma clearances for the two narcotics are nearly identical (1.04 l./kg/min for alphaprodine and 1.01 l./kg/min for meperidine). The apparent volume of distribution for alphaprodine is smaller than for meperidine (1.90 l./kg for alphaprodine and 3.37 l./kg for meperidine).

Adult↗
PubMedDate not supplied

Fentanyl pharmacokinetics in awake volunteers.

A single intravenous dose of fentanyl (either 2 or 4 micrograms/kg body weight) was given to 13 healthy, young volunteer subjects. Serum fentanyl concentration decreased in a triexponential pattern. The terminal half-times were 750 and 853 minutes, respectively. A three-compartment, open, mammillary model is proposed for fentanyl kinetics.

Adult↗
PubMedDate not supplied

Optimal frequency ranges for extracting information on autonomic activity from the heart rate spectrogram.

Heart rate variability spectrum analysis provides useful quantitative indices of neural control of the SA node. This method is attractive both for its simplicity and the lack of invasive instrumentation, particularly for human investigation. The differing spectral characteristics of parasympathetic and sympathetic control of heart rate allows separate measurement. However, there are widely varying opinions as to the appropriate frequency bands to represent these two inputs. We compared the heart rate variability spectra of 16 humans in supine and upright positions. Adequate measures of parasympathetic or sympathetic activity change should correlate respectively inversely or directly with heart rate change. Frequently used spectral measures of sympathetic activation did not correlate with heart rate changes. With optimization of frequency bands, we found that restricting the sympathetic band to frequencies below 0.1 Hz and above 0.05 Hz (0.055 to either 0.086-0.098 Hz), and dividing by total spectral amplitude 0.004-0.5 Hz (to account for parasympathetic fluctuations within the sympathetic band) produced the best results. The parasympathetic band was best from 0.1 Hz to a frequency greater than that of the respiratory sinus arrhythmia. The optimization method detailed here is easily applied to circumstances other than active orthostasis, and should provide a means of empirically determining useful frequency limits.

Adolescent↗
PubMedDate not supplied

Evaluating anatomical factors affecting endotracheal intubation.

Critically ill patients often require endotracheal intubation in the emergency department. Sometimes immediate attempts at endotracheal intubation are indicated. In other situations, a momentary delay to assess the anatomic factors that might make intubation difficult is advantageous. This examination should include assessment of nose and oral cavity patency, mobility and posterior depth of the mandible, and mobility and length of the neck.

Humans↗