Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 145 records · Page 8Linked to original sources

PubMed1995

Progress in traditional Chinese medicine.

Recently, traditional chinese medicine (TCM) natural products have been used to produce impressive responses in atopic eczema and related dermatological disorders that have proved resistant to orthodox treatments. The increasing popularity of TCM natural products has also produced fear about their toxicity and uncertainty about their ingredients. In the western world, very little is known of the efficacy and safety of TCM, and the legal responsibilities of practitioners are undefined. In this article Kelvin Chan overviews the TCM practitioners' concepts of how TCM natural products work and attempts to suggest the pharmacological interpretation of their mechanisms of action. The future of TCM is discussed by critically assessing the authenticity, quality, toxicity and clinical efficacy of these natural products.

Drugs, Chinese Herbal↗

PubMed1995

Intra- and inter-subject variabilities of CGP 33101 after replicate single oral doses of two 200-mg tablets and 400-mg suspension.

PURPOSE: The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subject variance to the overall variability. METHODS: Sixteen healthy subjects were randomly assigned to four groups to receive tablets and suspension twice in four different treatment sequences. The plasma concentration-time profile of CGP 33101 was characterized in terms of Cmax, Tmax, and AUC. Bioavailability of tablets relative to suspension and intra- and inter-subject variability were assessed by statistical analysis. RESULTS AND CONCLUSIONS: The overall variabilities in absorption kinetics of CGP 33101 in healthy subjects were small with CV's of the population mean values for AUC and Cmax less than 26% for both tablets and suspension. Contribution of intra-subject variability to the overall variability was also small (approximately 20%). Both the overall and intra-subject variabilities of AUC and Cmax after suspension were larger than after the tablets. However, the differences in variability between tablets and suspension were not statistically significant (p > 0.05). The tablet formulation was bioequivalent to suspension in terms of rate and extent of absorption based on 90% conventional confidence intervals (for AUC and Cmax) and Wilcoxon rank-sum test (for Tmax).

Administration, Oral↗

PubMed1995

Rapamycin: distribution, pharmacokinetics, and therapeutic range investigations.

Rapamycin (RAPA) is a potent immunosuppressive drug that is presently undergoing clinical trials. The most of the drug is sequestered in erythrocytes resulting in whole blood concentrations being considerably higher than plasma concentrations. The drug is metabolized by the same P450 3A enzyme that is involved in the metabolism of cyclosporine and tacrolimus. Structural elucidation of RAPA metabolites is required. The drug has a relatively long half-life in both humans and animals with 24-h trough concentrations being within the analytic range of high-performance liquid chromatography (HPLC) when immunosuppressive doses are administered. For RAPA, a proportionality is exhibited between trough concentrations and dose. In animal transplant models, trough concentrations of the drug appear to be related to immunosuppressive efficacy and drug-related side effects. The studies described here should provide the basis for establishment of therapeutic monitoring protocols for the drug.

Animals↗

PubMed1995

The effects of Danshen (Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetics of warfarin enantiomers in rats.

The effects of Danshen (Salvia miltiorrhiza), a popular traditional Chinese medicinal herb on the pharmacokinetics and pharmacodynamics of R- and S-warfarin stereoisomers were studied in rats. After a single oral dose of racemic warfarin (2 mg kg-1), treatment with oral Danshen extract (5 g kg-1, twice daily) for 3 days significantly altered the overall pharmacokinetics of both R- and S-warfarin and increased the plasma concentrations of both enantiomers over a period of 24 h and the prothrombin time over 2 days. At steady-state levels of racemic warfarin (0.2 mg kg-1 day-1 for 5 days) the 3-day treatment of Danshen extract (5 g kg-1, twice daily) not only prolonged the prothrombin time but also increased the steady-state plasma concentrations of R- and S-warfarin. The results indicate that Danshen extracts can increase the absorption rate constant, area under plasma concentration-time curves, maximum concentrations and elimination half-lives, but decreases the clearances and apparent volume of distribution of both R- and S-warfarin. The pharmacokinetic and pharmacodynamic interactions of warfarin during co-treatment with Danshen extract observed in this study indicate an explanation for the clinically observed incidents of exaggerated warfarin adverse effects when traditional Chinese medicinal herbs or herbal products such as Danshen and Danggui (observed in a previous study) were co-administered.

Acenocoumarol↗

PubMed1995

Ovine fetal swallowing response to intracerebroventricular hypertonic saline.

In the near-term ovine fetus, systemic hyperosmolality stimulates dipsogenic responses. Putative systemic dipsogens (hypertonicity, angiotensin II) may initiate responses by stimulation of select cerebral circumventricular nuclei lacking a blood-brain barrier. To investigate whether central osmotic-dipsogenic mechanisms are functional in utero, fetal swallowing responses to intracerebroventricular (i.c.v.) hypertonic saline were examined. Five pregnant ewes with singleton fetuses (128 +/- 1 days gestation) were prepared with fetal lateral cerebral ventricle and vascular catheters, electrocortical (ECoG) electrodes, and electromyogram wires on the fetal thyrohyoid muscle, nuchal and thoracic esophagus, and diaphragm and studied for a minimum of 5 days postoperatively. After a 2-h basal period, fetuses received an i.c.v. infusion of artificial cerebrospinal fluid followed by successive 30-min infusions of hypertonic NaCl in artificial cerebrospinal fluid (500 and 700 mosmol/kgH2O). In response to the i.c.v. hypertonic NaCl infusions, fetal swallowing significantly increased (1.4 +/- 0.4 to 3.9 +/- 1.4 and 2.9 +/- 0.5 swallows/min low-voltage ECoG, respectively). Plasma arginine vasopressin levels increased, although the change was not statistically significant (9.1 to 24.2 pg/ml; P = 0.07), and there was no change in fetal plasma osmolality, sodium concentration, or ECoG activity. Together with previous studies, these results indicate that both central and systemic osmotic dipsogenic mechanisms are functional in utero.

Animals↗

PubMed1995

BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats.

The effect of BPC-15 (Booly Protection Compound-15) was evaluated in a rat model of colonic injury. A single intracolonic administration of trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol induces severe colonic damage, which is characterized by areas of necrosis surrounded by areas of acute inflammation. The damage is associated with high myeloperoxidase (MPO) activity, mainly as a reflection of neutrophilic infiltration into the damaged tissue. In this study, 1 hr before a single intracolonic administration of 50 mg/kg of TNBS in 50% ethanol, the animals were treated with one of the following doses of BPC-15: 0.0001, 0.001, 0.01, 0.1, 1 or 10 nmol/kg administered i.p. or with a dose of 10 nmol/kg administered intracolonically. The animals were sacrificed 3 days later and the extent of colonic necrosis and hyperemia was measured with an image analyzer. The i.p. administration of BPC-15 significantly reduced the extent of TNBS-induced colonic damage in a dose-dependent manner. This was associated with a statistically significant and dose-dependent reduction in colonic tissue MPO activity. At the dose tested (10 nmol/kg), intracolonic administration of BPC-15 did not significantly reduce either the extent of the colonic damage or the increase in MPO activity induced by TNBS. In conclusion, this study showed that i.p. administration of BPC-15 reduced TNBS-induced colonic damage in rats.

Amino Acid Sequence↗

PubMed1995

A new, simple and accurate method for determining ejection fraction by Doppler echocardiography.

OBJECTIVE: To evaluate the feasibility, accuracy and reproducibility of a new and simple method for determining ejection fraction by Doppler echocardiography. This method should theoretically be less influenced by the distortions of left ventricular geometry caused by prior myocardial infarction. DESIGN: Two groups of patients (total 114) were evaluated independently at the Quebec and Ottawa Heart Institutes (60 and 54 patients, respectively). All were referred for radionuclide angiography performed within 24 h of the echocardiogram. Regional asynergy was present in 59% of Quebec patients and 37% of Ottawa patients. The new method for calculating ejection fraction consisted of dividing Doppler derived stroke volume in the left ventricular outflow tract by left ventricular end-diastolic volume calculated by Teichholz's formula; for comparison, ejection fraction was also measured by single plane area length or multiple disc planimetry as well as by the Quinones method at the Quebec Heart Institute. RESULTS: Feasibility of the new method was 97% in Quebec and 100% in Ottawa. Compared with radionuclide angiography, the correlation coefficient for the new method was 0.92 (standard error of estimate [SEE] = 7.3) in Quebec compared with 0.88 (SEE = 8.5 and 8.1) for both the Quinones and single plane area length methods, and 0.84 (SEE = 12.0) in Ottawa compared with 0.77 (SEE = 10.9) for the single plane multiple disc method. Correlations in patients with regional asynergy were 0.90 in Quebec and 0.75 in Ottawa compared with 0.81 and 0.54 with planimetry. Correlation coefficients for interobserver variability in 12 patients were 0.97 with the new method compared with 0.83 with the Quinones method and 0.85 with single plane planimetry. CONCLUSION: This new and simple method is feasible, accurate and reproducible even in patients with regional asynergy. Provided there is no significant mitral regurgitation, it is a time-saving alternative for the routine evaluation of ejection fraction by Doppler echocardiography.

Angiocardiography↗

PubMed1995

Correlation between steady-state plasma concentration of antituberculous drugs and age, inclusion of rifampicin in the treatment regimen, adverse drug reactions and other clinical parameters.

A regional hospital in Hong Kong examined the correlation between plasma concentrations of rifampicin, pyrazinamide, isoniazid and its metabolite hydrazine and age, inclusion of rifampicin in the treatment regimen, adverse drug reactions and other clinical parameters. One hundred eighty subjects with tuberculosis were admitted consecutively to the medical wards of the Prince of Wales Hospital over a one and a half year period. Elderly patients > 65 years were randomized into one of two treatments with and without rifampicin in addition to isoniazid, pyrazinamide and ethambutol; younger patients received all four drugs. Plasma antituberculous drug concentrations were determined using high performance liquid chromatography. Elderly patients taking rifampicin had a higher mean steady-state concentration of isoniazid, together with a higher incidence of adverse effects compared with those not taking rifampicin. No age related differences were observed for the other drugs. For the whole group, higher mean concentrations of hydrazine, rifampicin and pyrazinamide were associated with a higher incidence of adverse effects and the presence of coexisting diseases. It is concluded that in sick elderly patients with coexisting diseases, use of rifampicin in the antituberculous regimen should be accompanied by close monitoring for side effects, and that there may be an indication for use of lower dosages of antituberculous drugs in such patients.

Adult↗

PubMed1994

Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region.

Hypersensitive site 2 located in the beta-globin locus control region confers high levels of expression to the genes of the beta-globin cluster. A tandem repeat of the consensus sequence for the transcription factors AP1 and NF-E2 (activating protein 1 and nuclear factor erythroid 2, respectively) is present within hypersensitive site 2 and is absolutely required for strong enhancer activity. This sequence binds, in vitro and in vivo, to ubiquitous proteins of the AP1 family and to the recently cloned erythroid-specific transcription factor NF-E2. Using the tandem repeat as a recognition site probe to screen a lambda gt11 cDNA expression library from K562 cells, we isolated several DNA binding proteins. Here, we report the characterization of one of the clones isolated. The gene, which we named Nrf2 (NF-E2-related factor 2), is encoded within a 2.2-kb transcript and predicts a 66-kDa protein with a basic leucine zipper DNA binding domain highly homologous to that of NF-E2. Although Nrf2 is expressed ubiquitously, a role of this protein in mediating enhancer activity of hypersensitive site 2 in erythroid cells cannot be excluded. In this respect, Nrf2 contains a powerful acidic activation domain that may participate in the transcriptional stimulation of beta-globin genes.

Amino Acid Sequence↗

PubMed1994

Effect of food on the relative bioavailability of a hypolipidemic agent (CGP 43371) in healthy subjects.

The relative bioavailability of a capsule formulation and the effects of food on the pharmacokinetics of a hypolipidemic agent (CGP 43371) in 12 healthy subjects were examined. Each subject randomly received a single dose of 800 mg of CGP 43371, either as a dispersion formulation under fasting conditions or as a capsule formulation under fasting and fed conditions in a three-way crossover design with a washout period of 2 weeks between each treatment. Serial blood samples were collected at frequent intervals up to 96 h after each treatment. The concentrations of CGP 43371 in plasma were determined by a normal-phase HPLC method. Similar mean pharmacokinetic data (peak plasma drug concentration, 0.16 versus 0.18 micrograms/mL; area under the plasma drug concentration-time curve from time zero to infinity, 4.56 versus 4.22 micrograms.h/mL; time to the peak plasma drug concentration, 10.3 versus 10.2 h; lag time, 3.7 versus 3.8 h; and terminal elimination half-life, 17.8 versus 15.0 h) for the dispersion and capsule formulations under fasting conditions indicated that both formulations were bioequivalent with respect to the rate and extent of absorption. In contrast, the mean peak plasma drug concentration (2.01 micrograms/mL) and area under the curve from time zero to infinity (57.35 micrograms.h/mL) for the capsule formulation with food were enhanced approximately 11- and 14-fold, respectively, when compared with that without food. The corresponding mean lag time (2.1 h) was decreased approximately 50%. These differences in pharmacokinetic parameters were statistically significant, on the basis of an analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗

PubMed1994

Phase I and pharmacologic study of liposomal daunorubicin (DaunoXome).

We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial dose-escalation steps from 10 to 60 mg/m2. At 80 mg/m2, two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m2. Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m2 in previously treated and 120 mg/m2 of DaunoXome in previously untreated patients with solid tumors.

Adult↗

PubMed1994

Somatosensory evoked response source localization using actual cortical surface as the spatial constraint.

We localized right median nerve somatosensory evoked responses in a normal human subject using an equivalent dipole method applied to magnetic field recordings. High resolution, 3-dimensional MRI data were used to confine source locations to the cortical surface. Results localized in Brodmann area 3b corresponding to location of hand somatosensory cortex derived from direct brain stimulation studies. The solution was unique and total computational time for an exhaustive, brute-force search was small and the results realistic due to applied anatomical constraints. This study demonstrates feasibility of accurate, non-invasive, realistic localization of dynamic human cortical function using spatial constraints provided by MRI images.

Adult↗

PubMed1994

Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects.

Pharmacokinetic interaction between benazepril (ACE inhibitor) and amlodipine (calcium channel blocker) was studied in 12 healthy subjects. Single doses of benazepril hydrochloride (10-mg tablet) and amlodipine besylate (tablet equivalent to 5 mg amlodipine) were administered alone or in combination according to a three-way, Latin-Square, randomized cross-over design. Serial blood samples were collected following each administration for the determination of benazepril and its active metabolite benazeprilat and amlodipine. The mean values of AUC (0-4 h), Cmax and Tmax for benazepril given as combination versus given alone were 161 vs 140 ng.h.ml-1, 168 vs 149 ng.ml-1, and 0.5 vs 0.6 h. The mean values of AUC (0-24 h), Cmax and Tmax for benazeprilat after benazepril given as combination versus given alone were 1470 vs 1410 ng.h.ml-1, 292 vs 257 ng.ml-1, and 1.7 vs 1.5 h. The mean values of AUC (0-144 h), Cmax and Tmax for amlodipine given as combination versus given alone were 118 vs 114 ng.h.ml-1, 2.5 vs 2.3 ng.ml-1, and 8.3 vs 9.0 h. The differences in these pharmacokinetic parameters between the combination and monotherapy treatments were not statistically significant based on ANOVA. The results of this study indicate that no pharmacokinetic interaction existed between the two drugs.

Adult↗

PubMed1994

Central angiotensin II stimulation of ovine fetal swallowing.

In the late-gestation ovine fetus, spontaneous swallowing occurs primarily during fetal low-voltage electrocortical (ECoG) activity in association with fetal breathing movements. Fetal swallowing activity may be stimulated in response to systemic or carotid plasma hyperosmolality, although not to increased plasma angiotensin II (ANG II) levels. In view of the potent dipsogenic effects of central, but not peripheral, ANG II in adult sheep, the present study investigated the effect of intracerebroventricular (ICV) ANG II on fetal swallowing activity. Six ovine fetuses (127 +/- 1 days) were chronically prepared with electromyogram and cortical electrodes and with vascular and lateral ventricle catheters. After a 2-h control period, fetuses received ICV injections of artificial cerebrospinal fluid and increasing concentrations of ANG II (0.1, 1.0, 10, 100, and 500 ng/kg). Fetal ECoG activity did not change, although fetal swallowing activity significantly increased in response to the 100- and 500- ng/kg ANG II doses (1.20 +/- 0.14 to 3.34 +/- 0.59 and 3.46 +/- 0.81 swallows/min of low-voltage ECoG, respectively). In response to the highest ANG II dose, fetal plasma arginine vasopressin levels significantly increased (5.7 +/- 1.2 to 17.2 +/- 4.6 pg/ml). ICV ANG II stimulation of fetal swallowing and arginine vasopressin secretion demonstrates that central ANG II dipsogenic mechanisms are intact by 0.9 of ovine gestation.

Amniotic Fluid↗

PubMed1994

Detection of aneuploidy in human sperm by fluorescence in situ hybridization (FISH): different frequencies in fresh and stored sperm nuclei.

Fluorescence in situ hybridization (FISH) with chromosome-specific repetitive DNA probes provides a new method for rapid detection of aneuploidy in human sperm. There is widespread interest in this technique for basic research, as well as for screening men exposed to potential aneugens. A number of laboratories have reported a wide range in the frequency of aneuploidy for chromosomes in human sperm, suggesting that FISH may not reflect the true frequency accurately. We have serendipitously discovered that the length of time that fixed frozen sperm nuclei are stored affects both the hybridization efficiency and disomy frequency of individual chromosomes. This may explain some of the variation in the aneuploidy frequencies observed among laboratories.

Aneuploidy↗

PubMed1994

The influence of age on aerosol deposition in children with cystic fibrosis.

Nebulized aerosols are commonly used to deliver drugs for the treatment of respiratory disease in children, but there are inadequate data on the dose of drug depositing in the lungs in this age group, and the effect of age on this dose. We therefore aimed to quantify total and regional deposition of nebulized aerosol in children of widely differing age. Twelve infants (median age 0.8 yrs, range 0.3-1.4 yrs) who were asleep, and eight older children (median age 10.8 yrs, range 6.3-18.0 yrs) with cystic fibrosis were studied. Radiolabelled normal saline aerosol was generated by a Turret nebulizer, with a driving flow of 9 l.min-1. All subjects inhaled aerosol via the nasal route, whilst the older children undertook a second study with inhalation via the oral route. Following aerosol inhalation, planar and single-photon emission computed tomography (SPECT) scans were obtained. For the nasal route, total lung deposition was lower in infants (median 1.3%, range 0.3-1.6%) than in older children (median 2.7%, range 1.6-4.4%). For the older children inhaling via the nasal or oral route, there was no influence of age on lung, upper respiratory tract, or the sum of upper respiratory tract and lung deposition. We conclude that the dose of a nasally inspired aerosol reaching the lungs of infants who are asleep is approximately half that for older children, when the nebulizer is operating at 9 l.min-1. Age does not affect deposition of nasally or orally inspired aerosols in older children.

Administration, Inhalation↗

PubMed1994

The respiratory depressant effect of morphine. A comparative study in three ethnic groups.

The respiratory response to carbon dioxide was measured in 130 ASA 1 adult male patients from three ethnic groups, European, Nepalese, and Chinese, both before and after premedication with intramuscular morphine sulphate (200 micrograms.kg-1 body weight). Satisfactory results were obtained from 125 patients. Overall, there was no ethnic difference in the effect of morphine on the respiratory response to carbon dioxide, but initially the Chinese group appeared to be more sensitive in their response to carbon dioxide than the Europeans and Nepalese. However, there was a significant correlation between respiratory response to carbon dioxide and pulse rate and on restricting analysis to those patients with a pulse rate equal to or less than 72 beat.min-1, the ethnic difference in carbon dioxide response disappeared. It was concluded that there were no ethnic differences in the respiratory response to carbon dioxide before or after morphine in male Europeans, Nepalese and Chinese but that the respiratory response to carbon dioxide may be influenced by long term physical training.

Adolescent↗

PubMed1993

Simultaneous determination of flumazenil, midazolam and metabolites in human biological fluids by liquid chromatography.

A simple procedure for the simultaneous determination of flumazenil, midazolam, 1-hydroxymethylmidazolam and 4-hydroxymidazolam in plasma or urine in surgical patients is described. The assay involves a preliminary extraction of the drugs, metabolites and internal standard (flurazepam) from biological fluid into an organic solvent mixture (dichloromethane-diethyl ether, 40:60 v/v). The extract was evaporated to dryness at 40 degrees C under a gentle stream of nitrogen. The residue was re-dissolved in distilled methanol (80 microliters) and a 30-microliters aliquot was injected via an automatic sampler into the liquid chromatograph and eluted with the mobile phase (32% acetonitrile in 0.004 M sodium hydrogenphosphate buffer containing 1 ml of triethylamine and adjusted to pH 7.2) at a flow-rate of 1.5 ml/min on a 30-microns C8 precolumn linked to a 4-microns Nova-pak C18 cartridge column (100 mm x 8 mm I.D.) at ambient temperature (25 degrees C). The eluate was detected at 220 nm.

Child↗