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Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 163 records · Page 9Linked to original sources
PubMed1993

Urinary excretion of aminohydroxypropylidene bisphosphonate in cancer patients after single intravenous infusions.

The effect of the rate of infusion of disodium aminohydroxypropylidene bisphosphonate (APD; CGP 23339A), an inhibitor of bone resorption, on urinary excretion of this agent was studied in a randomized open-label study in 20 cancer patients. Ten patients received 60 mg of APD over 4 h, and the remaining 10 patients received the same dose over 24 h. Urine collected during specified intervals for 72 h after the start of the infusion was analyzed by high-performance liquid chromatography for unchanged APD. Mild and transient adverse experiences were observed in 12 (60%) patients; the most common were headache, fever, and phlebitis at the infusion site. No clinically significant laboratory abnormalities were observed, and none of the experiences were serious enough to require discontinuation of treatment. Cumulative urinary excretion of APD was a linear function of time, increasing rapidly after both the 4- and 24-h infusions were started. The mean (+/- standard deviation) cumulative urinary excretion of APD was 51.1 +/- 13.0% of the dose in the 20 patients, 55.0 +/- 15.0% in the 10 patients given the 4-h infusion, and 47.2 +/- 9.9% in the 10 patients receiving the 24-h infusion. Thus, the rate of infusion of the 60-mg dose did not influence retention of APD at 72 h after the start of therapy. Similarly, the presence or absence of bone metastases did not influence cumulative urinary excretion or the retention of APD.

Adult↗
PubMed1993

A retrospective study of endodontically treated mandibular first molars in a Chinese population.

The purpose of this investigation was to study the prevalence of three roots and four root canals in the mandibular first molars of a Chinese population. A total of 832 cases of mandibular first molars that had received root canal treatment clinically were examined by reviewing the clinical records and radiographs. The results showed that: (a) Mandibular first molars with four root canals occur at a frequency of 31.5%. (b) More than two-thirds (68.3%) of the above cases had the fourth canal arising from the third root, an extradistal root. (c) The bilateral occurrence of this extradistal root in mandibular first molars was 67%. In conclusion, the occurrence of four root canals in mandibular first molars among Chinese people was not unusual.

Asian People↗
PubMed1993

Human transbuccal absorption of diclofenac sodium from a prototype hydrogel delivery device.

The buccal delivery of the nonsteroidal antiinflammatory drug, diclofenac sodium (Voltaren), from a prototype hydrogel was studied in man in a randomized crossover design of buccal delivery and i.v. infusion. After a 30-min delay, plasma levels of diclofenac increased to near steady-state levels of 100 ng/ml by 3 hr. With each subject serving as his own control, the i.v. infusion data facilitated the calculation of a mean steady-state flux of diclofenac sodium of 2.1 +/- 0.6 mg/cm2-hr across human buccal mucosa and a time lag of 1.0 +/- 0.5 hr. The large flux of this ionized species indicates that the traditional lipoidal model of buccal permeation based on the partition coefficient is inadequate.

Absorption↗
PubMed1993

Pharmacokinetics of flumazenil and midazolam.

We have studied simultaneously the pharmacokinetics of flumazenil and midazolam in 12 healthy Chinese children, aged 5-9 yr, undergoing circumcision. Two hours before operation each patient received midazolam 0.5 mg kg-1 orally for premedication and 0.5 mg kg-1 i.v. during induction. Six minutes after cessation of anaesthesia, a bolus of flumazenil 10 micrograms kg-1 was given i.v., followed by an infusion of flumazenil at 5 micrograms kg-1 min-1 which was maintained until the child could identify himself. Midazolam data were consistent with a three-compartment model with a mean (SD) elimination half-life of 107 (30) min, total body clearance of 15.4 (3.2) ml min-1 kg-1 and apparent volume of distribution at steady state of 1.9 (0.6) litre kg-1. Flumazenil data were best interpreted by a monoexponential function, with a mean terminal elimination half-life of 35.3 (13.8) min, a total plasma clearance of 20.6 (6.9) ml min-1 kg-1 and apparent volume of distribution at steady state of 1.0 (0.2) litre kg-1. No unchanged midazolam was detected in the 24-h urine sample, but 5.8-13.8% of the flumazenil dose was recovered unchanged. At the time of self identification, 4.5 (1.4) min after flumazenil administration, the mean plasma concentrations of midazolam and flumazenil were 163.1 (43.7) and 29.9 (16.1) ng ml-1, respectively.

Child↗
PubMed1993

Detection of aneuploidy in human interphase spermatozoa by fluorescence in situ hybridization (FISH).

Fluorescence in situ hybridization (FISH) with repetitive-sequence DNA probes was performed on human interphase sperm to determine the utility of this technique for aneuploidy detection. DNA sequences specific for chromosomes 15 and 16 and the Y were biotinylated and hybridized with human sperm that had been treated with cetyltrimethylammonium bromide and dithiothreitol to render them accessible to the probes. Fluoresceinated avidin and antiavidin were utilized to visualize bound probe. More than 10,000 sperm were analyzed for each chromosome probe. The hybridization efficiency was 98-99% for all three probes. The frequencies for disomy (i.e., for nuclei containing two fluorescent signals) for chromosomes 15 and 16 and the Y were 0.14%, 0.17%, and 0.11%, respectively. These frequencies are all somewhat higher than those obtained by the human sperm karyotyping technique. Nevertheless, these preliminary results suggest that FISH is a simple and rapid technique that may provide an accurate screen for aneuploidy detection in human sperm.

Aneuploidy↗
PubMed1992

Pharmacokinetics of ara-C and ara-U in plasma and CSF after high-dose administration of cytosine arabinoside.

Cytosine arabinoside (ara-C) and uracil arabinoside (ara-U) levels were measured in the plasma, cerebrospinal fluid (CSF), and urine of 10 patients exhibiting primary central nervous system lymphoma who received 31 infusions of high-dose ara-C (3 g/m2) as part of their treatment regimen. Peak plasma and CSF ara-C levels were 10.8 and 1.5 micrograms/ml, respectively. Ara-C was cleared more rapidly from plasma than from CSF. Ara-U appeared rapidly in both plasma and CSF, reaching a peak that was 10 times higher than the corresponding ara-C concentration (104 and 11.2 micrograms/ml, respectively). Only 4%-6% of the dose was excreted unchanged in the urine, but 63%-73% of it appeared as ara-U within the first 24 h. The presence of leptomeningeal lymphoma did not affect the CSF level of ara-C or ara-U.

Arabinofuranosyluracil↗
PubMed1992

Fetal catecholamine, cardiovascular, and neurobehavioral responses to cocaine.

OBJECTIVE: Although maternal cocaine administration results in fetal cardiovascular and behavioral alterations, these responses have been attributed to hypoxia resulting from reduced uteroplacental blood flow. We studied the fetal catecholamine, cardiovascular, and neurobehavioral responses to direct fetal cocaine administration. STUDY DESIGN: Cardiovascular, electrocortical, and electroocular responses and plasma catecholamines were monitored in chronically catheterized fetal sheep (n = 7), 127 +/- 2 days' gestation, during a control period and after intravenous fetal injections of cocaine 0.5 and 1.0 mg/kg. RESULTS: Intravenous cocaine caused prompt increases in fetal plasma norepinephrine (372 +/- 73 to 531 +/- 112 and 842 +/- 233 pg/ml), epinephrine (27 +/- 7 to 46 +/- 13 and 49 +/- 11 pg/ml), and systolic blood pressure (46 +/- 2 to 53 +/- 2 and 55 +/- 2 mm Hg). Low-voltage electrocortical activity decreased from 61.7% +/- 3.0% to 38.4% +/- 3.9% in the first hour after the cocaine 0.5 mg/kg dose but recovered to baseline values during the second hour. After the cocaine 1.0 mg/kg dose, low-voltage electrocortical activity decreased to 40.7% +/- 2.0% and did not recover thereafter. Fetal blood gas values did not change. CONCLUSION: Direct fetal cocaine administration increases fetal plasma catecholamine levels and fetal blood pressure and suppresses low-voltage electrocortical activity. Chronic cocaine exposure may hamper central nervous system maturation and alter postnatal development.

Animals↗
PubMed1992

Dehydration increases the renal response to atrial natriuretic peptide in fetal sheep.

OBJECTIVE: In sheep, maternal water deprivation results in urinary natriuresis in spite of suppression of plasma atrial natriuretic factor levels. Near-term fetal sheep also have a urinary natriuresis without change in plasma atrial natriuretic factor during maternal dehydration. This study was designed to explore the role of plasma atrial natriuretic factor levels in fetal dehydration-natriuresis. STUDY DESIGN: Eight chronically instrumented preterm (113 +/- 1 days) ovine fetuses received two atrial natriuretic factor infusions (3 and 15 ng/kg/min) in a euhydrated state and after 48 +/- 1 hours of maternal water deprivation. RESULTS: Dehydration significantly increased maternal plasma osmolality (302 +/- 2 to 313 +/- 2 mOsm/kg water), sodium (148.1 +/- 0.8 to 154.3 +/- 0.4 mEq/L), chloride (112.4 +/- 0.6 to 116.8 +/- 0.9 mEq/L), and arginine vasopressin (4.2 +/- 1.2 to 23.0 +/- 4.0 pg/ml) and significantly decreased plasma atrial natriuretic factor (36 +/- 6 to 19 +/- 4 pg/ml) concentrations. Fetal plasma osmolality (296 +/- 1 to 308 +/- 2 mOsm/kg), atrial natriuretic factor (128 +/- 16 to 241 +/- 36 pg/ml), and arginine vasopressin (3.5 +/- 0.8 to 12.3 +/- 4.8 pg/ml) concentrations and urine osmolality (170 +/- 10 to 253 +/- 10 mOsm/kg), osmolar clearance (0.80 +/- 0.02 to 0.14 +/- 0.02 ml/kg/min), and fractional sodium excretion (3.3% +/- 1.7% to 8.5% +/- 2.1%) increased significantly with dehydration, whereas the plasma atrial natriuretic factor clearance decreased from 127 +/- 27 to 63 +/- 10 ml/kg/min. Dehydration had no effect on fetal hematocrit, vascular pressures, glomerular filtration rate, urine flow, or free water clearance. In euhydrated fetuses plasma atrial natriuretic factor increased from 128 +/- 16 to 287 +/- 46 pg/ml with sequential atrial natriuretic factor infusion, and no significant increases were observed in urine flow, fractional sodium excretion, and glomerular filtration rate. In contrast, atrial natriuretic factor infusion to dehydrated fetuses significantly increased urine flow (0.17 +/- 0.03 to 0.32 +/- 0.07 ml/kg/min), osmolar clearance (0.14 +/- 0.02 to 0.28 +/- 0.06 ml/kg/min), and fractional sodium excretion (8.5% +/- 2.1% to 14.8% +/- 4.0%). CONCLUSION: These results demonstrate that in the fetus at 113 days' gestation plasma atrial natriuretic factor levels increase with dehydration, probably a result of decreased plasma atrial natriuretic factor clearance, and the fetal renal responsiveness to atrial natriuretic factor infusion increases during maternal dehydration.

Animals↗
PubMed1992

The use of a packed column for the determination of bupivacaine in human plasma by gas chromatography: an application in a pharmacokinetic study of bupivacaine.

The method involves a single extraction of the drug and the internal standard, etidocaine, from alkalinized plasma with n-hexane. The gas chromatograph is equipped with a glass column (2.0 m x 2 mm) packed with 3% W/W SP2250 on Chromosorb W, (80/100 mesh) and a nitrogen sensitive detector. The method can accurately measure plasma bupivacaine concentrations down to 0.01 micrograms ml-1 using a sample size of 0.5 ml. The day-to-day variation of bupivacaine at 2.0 micrograms ml-1 is 6.90% (n = 10). The calibration graph is linear over the range 0.1-4.0 micrograms ml-1. The method is accurate, fast and sensitive and has been applied in a pharmacokinetic study of bupivacaine.

Absorption↗
PubMed1992

Prechewing of food by adults and streptococcal pharyngitis in infants.

Three infants with group A streptococcal pharyngitis were found to have eaten food prechewed by their parents. One parent had a history of recent pharyngitis and another had frequent episodes of tonsillitis. Prechewing of babies' food, which may be more common in the United States than is generally recognized, may be a mode of transmission of group A streptococcal pharyngitis to infants.

Adult↗
PubMed1992

Mandibular premolar with three root canals--two case reports.

The presence of three root canals in the mandibular premolar may sometimes be recognized when there is persistent postoperative discomfort following root canal therapy. This paper presents two cases of root canal treatment of mandibular premolars with three root canals including one mandibular first premolar and one mandibular second premolar. The possibility that there is more than one root canal in lower premolar teeth must be considered in the radiographic and clinical examination during root canal treatment.

Adult↗
PubMed1992

Dispositional study of opioids in mice pretreated with sympathomimetic agents.

Brain and plasma levels of morphine and codeine were determined by an assay method involving solid-phase extraction and ion-pair reversed phase HPLC. Detection was by a variable wavelength UV-detector (for codeine) and an amperometric electro-chemical detector (for morphine) coupled in series. Ephedrine or phenylpropanolamine pretreatment did not interfere with the plasma disposition of morphine, evidenced by overlapping plasma concentration-time profiles. Brain opioid levels were equally unaffected by sympathomimetic pretreatment. The relative ratios of brain to plasma concentrations at the time corresponding to the respective peak anti-nociceptive activity for morphine and codeine revealed no significant differences. It is concluded that single doses of ephedrine and phenylpropanolamine do not affect the disposition of morphine and codeine in mice.

Animals↗
PubMed1992

Simultaneous determination of bufadienolides in the traditional Chinese medicine preparation, liu-shen-wan, by liquid chromatography.

The bufadienolide compounds (bufalin, cinobufagin and resibufogenin), major constituents of Chansu in Liu-Shen-Wan (LSW), were determined by reverse phase high performance liquid chromatography. The procedure involves a preliminary extraction of the bufadienolides from LSW with chloroform using ultrasonication and subsequent evaporation to dryness of the chloroform extract. The residue of the chloroform extract was dissolved in methanol and separated on a Merck LiChrosorb RP-18 column. Methanol: water (74:26) was used as mobile phase. The compounds were satisfactorily separated with good chromatographic peaks. Good coefficients of correlation (r > 0.999) were obtained from the calibration of peak areas with concentrations for the 3 bufadienolides. Results of analysis showed that there were differences between the contents of bufadienolides in 11 LSW samples of different origin available to the public in Hong Kong where at present there is no legal control over the sale of traditional Chinese medicines. The variability of quantities of bufadienolides in Chansu may be a hazard to the public.

Bufanolides↗
PubMed1992

Effects of inverse ratio ventilation on cardiorespiratory parameters in severe respiratory failure.

Inverse ratio ventilation, with prolonged inspiratory times, appears to improve gas exchange and arterial oxygenation in patients with severe respiratory failure; however, in previous studies, pressure-controlled inverse ratio ventilation (PC-IRV), which uses a rapidly decelerating inspiratory flow pattern, was compared to conventional volume-controlled ventilation, which uses a constant inspiratory flow rate. Pressure-controlled ventilation (PCV), with a decelerating inspiratory flow pattern and conventional inspiratory-to-expiratory (I/E) ratios, also has been shown to produce improvement in PaO2 when compared to volume-controlled ventilation. It therefore is unknown if the potentially beneficial effects of PC-IRV are due to the reversal of I/E ratios or to the use of the rapidly decelerating inspiratory flow pattern. In order to investigate this issue, cardiorespiratory values were measured in ten patients with severe respiratory failure ventilated first with PCV, then PC-IRV, and finally with a second period of PCV. Tidal volume, respiratory rate, end-expiratory pressure, and fraction of oxygen in inspired gas (FIO2) were maintained at the same value for both ventilatory modalities. The PC-IRV was associated with significant increases in PaO2, arterial pH, and mean airway pressure. Significant decreases in pulmonary shunt fraction, PaCO2, and cardiac index were found with PC-IRV. No significant changes in tissue oxygen delivery or consumption occurred with either PCV or PC-IRV. These results demonstrate that inversion of conventional I/E ratios produces no significant improvement in the overall cardiorespiratory profile of critically ill patients. This study also suggests that the clinical utility of PC-IRV is limited except in the setting of the adult respiratory distress syndrome with hypoxemia or hypercapnia refractory to other therapeutic options.

Adult↗
PubMed1992

Further metabolic studies of codeine and morphine in mice pretreated with sympathomimetics.

The effects of ephedrine and phenylpropanolamine (PPA) on the 24 h urinary excretion of morphine, codeine and their metabolites, and on the plasma and brain disposition of morphine and codeine at steady state in mice were studied. Morphine-3-glucuronide was the major urinary metabolite in morphine treated animals, while for codeine treated animals norcodeine and morphine-3-glucuronide were the major metabolites. In all cases percentage of drug excreted unchanged was 10-15% of the administered dose. Ephedrine or PPA pretreatment had no apparent effect on these parameters. The metabolic ratios for the different pathways were comparable in all treatment groups. Steady-state plasma and brain concentration-time profiles of codeine and morphine also showed marked similarity in all treatment groups. Apparently, ephedrine or PPA pretreatment has no effect on the disposition of morphine and codeine in mice. The results are discussed from the perspective of our earlier findings of dependence on cough mixtures containing opioids and sympathomimetics.

Animals↗
PubMed1992

Pharmacokinetics of epirubicin emulsion and solution in rabbits after intrahepato-arterial and intravenous injection.

The study reports pharmacokinetic findings on the disposition of a formulated emulsion of epirubicin in rabbits as compared to plain epirubicin solution after intrahepato-arterial and intravenous administration. The dose of epirubicin used was 1 mg/kg body weight. Blood samples were collected at several time points up to 6 h after administration. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUC infinity 0) is smallest after intrahepato injection of epirubicin emulsion. This, together with the highest apparent volume of distribution (Vss) suggest a possible targetting effect. Although the mean residence times are similar, intrahepato injection of emulsion apparently has the largest clearance. Difference in bioavailability in the general circulation between the 2 routes of administration also suggests a certain degree of liver first-pass metabolism of the drug. In view of these findings, further investigation and assessment are worthwhile for future application in human subjects.

Animals↗