Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 199 records · Page 11Linked to original sources

PubMed1991

Overview: new methods in imaging osteoarthritis.

The new imaging modalities, namely computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography (US) provide potentially powerful tools for in vivo assessment of osteoarthritis (OA), monitoring the progress of the disease and understanding its natural course. However, to use these tools effectively, we need more prospective research focused on correlating imaging data with biochemical and gross and microscopic pathologic findings. MRI is clearly the most powerful tool for demonstrating the various articular components which may be affected in OA. CT is excellent for delineating osseous abnormalities and with US we are able to evaluate the thickness and surface characteristics of those portions of articular cartilage that are accessible. The advantages and limitations of these 3 modalities are discussed as they pertain to OA of the hip and knee.

Arthrography↗

PubMed1991

The pharmacokinetics of isoniazid and hydrazine metabolite in plasma and cerebrospinal fluid of rabbits.

The pharmacokinetics of isoniazid (INH) and hydrazine metabolite (HYD) in plasma and cerebrospinal fluid (CSF) of ten rabbits was studied after separate intravenous (i.v.) and oral (p.o.) administration in a crossover study. The concentrations of INH and HYD in the biological fluids were determined by high performance liquid chromatography (HPLC). There was no difference in the area under plasma concentration-time curves, indicating that oral absorption was complete. The mean apparent volume of distribution after i.v. (3.02 +/- 0.55 L) was smaller (p less than 0.01) than that after p.o. (4.29 +/- 1.25 L) dosing. The elimination t1/2 of INH in CSF was longer (p less than 0.005) than that in plasma after either route of administration. There was no significant barrier to the penetration of INH into the CSF from the general circulation. The HYD plasma concentrations were similar after either route. HYD was eliminated at a slower rate (Ke = 0.17 h-1) than INH (Ke = 0.59 h-1). There was prolonged exposure of the body to HYD (greater than 6 h - above 0.1 micrograms/ml).

Administration, Oral↗

PubMed1990

Dynamic stress response of the implant/cement interface: an axisymmetric analysis of a knee tibial component.

To determine the adverse effects on the implant/cement interface stresses caused by a dynamic load on the implant, an axisymmetric dynamic finite element analysis was performed for an idealized knee tibial component assuming perfect bonding at the interface. The component, consisting of a metal plate with a central stem, was subjected to a compressive load that varied with time as a terminated ramp function. At first, the reliability of the interface stress predictions was assessed by computing the effects of a number of method-related parameters, viz., the finite element mesh density, the assumed bone properties. Analysis was then performed considering the stem length, cement mantle thickness, and the type of implant metal as design variables. The analysis predicts high-frequency (600 Hz) stress oscillations of significant amplitude at those locations of the interface that are also subjected to high static stresses: near the stem-plate junction and the stem tip for normal stress, and at the stem tip for shear stress. However, the predicted stress amplitude has been found to be particularly sensitive to the assumed rise time of the input load function. With a rise time of 2.0 ms, an input condition considered to be severe enough to represent the most vigorous dynamic activity, the maximum stress augmentation, because of stress oscillations, is predicted to be less than 25%. In general, the design variables have been found to affect the static stresses much more than the dynamic ones. It has been concluded that for the cases studied, dynamic effects are relatively small and a static analysis is sufficient to characterize the interface stress condition.

Aged↗

PubMed1990

Flavone acetic acid and plasma protein binding.

Both the capacity of healthy human, cancer patient, and mouse plasma proteins to bind flavone acetic acid (FAA) and the qualitative differences in the plasma protein-binding site were studied. The binding capacity of plasma proteins for FAA was saturated within the therapeutic range in both species. The binding of FAA to plasma protein was significantly greater in both healthy human and cancer patient plasma than in mouse plasma. Plasma from patients with cancer bound on the average less FAA than did healthy patient plasma. The concentration of albumin in the plasma varied between healthy humans, cancer patients, and mice, being 5.3 +/- 0.7, 4.7 +/- 0.8, and 3.9 +/- 0.3 g/100 ml, respectively. The protein binding of FAA was found to be dependent on the plasma albumin concentration, but albumin concentration alone was not adequate for the accurate prediction of the percentage of FAA protein bound. Scatchard plots indicated that healthy human plasma had a greater number of high-affinity binding sites than did mouse plasma. FAA binds at the indolebenzodiazepine binding area on albumin and can be displaced from this site by salicylic acid and clofibric acid, but only at supratherapeutic concentrations. Our results indicate that alterations in plasma albumin could contribute to a variable effect with FAA. Therefore, the influence of serum albumin concentration and the nonlinearity of FAA protein binding should be considered in assessment of the appropriateness of a dose schedule for FAA.

Animals↗

PubMed1990

Propofol infusion anaesthesia for caesarean section.

Two propofol infusion regimens and a standard general anaesthetic were compared in thirty Chinese women undergoing elective Caesarean section. After induction of anaesthesia with propofol 2 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 and nitrous oxide 50 per cent in oxygen while ten were given propofol 9 mg.kg-1.hr-1 with 100 per cent oxygen. The other ten patients received thiopentone 4 mg.kg-1 and nitrous oxide 50 per cent in oxygen with enflurane one per cent. Maternal recovery times and psychomotor performance were recorded. Neonates were assessed by Apgar scores, neurologic and adapative capacity scores (NACS) and umbilical cord blood gas analysis. Haemodynamic changes were similar immediately following induction but the low propofol infusion group had the best haemodynamic stability subsequently. Recovery times were fastest in the low-infusion group but there were no differences in later postbox testing. Neonatal Apgar scores and umbilical blood gas analysis were similar but NACS at two hours were poorer in the high infusion group. A propofol infusion coupled with nitrous oxide appears to be a satisfactory technique for Caesarean section.

Adult↗

PubMed1990

Pharmacokinetics of propofol in women undergoing elective caesarean section.

We have compared the pharmacokinetics of a bolus induction dose of propofol 2 mg kg-1 in 10 Chinese women undergoing elective Caesarean section with those in six non-pregnant Chinese women having laparoscopic sterilization. Blood propofol concentrations were measured using high pressure liquid chromatography with fluorimetric detection. Pharmacokinetic data were analysed by a model independent method based on statistical moment theory. Data from the laparoscopy group also underwent compartmental analysis, which produced similar kinetic results. Non-compartmental analysis estimated that the women undergoing Caesarean section had a similar elimination half-life (mean 81.27 (SD 18.87) min) and apparent volume of distribution at steady state (2.66 (0.63) litre kg-1) as non-obstetric patients (99.45 (29.40) min and 3.36 (1.87) litre kg-1). Clearance was more rapid in the Caesarean section group (39.32 (8.07) ml min-1 kg-1 vs 29.40 (8.72) ml min-1 kg-1) (P less than 0.05). The increased total body clearance may result from blood loss and delivery of the fetus and placenta at operation, although an increase in extrahepatic clearance is also possible.

Adult↗

PubMed1990

Effect of adrenaline on venous plasma concentrations of bupivacaine after interpleural administration.

Bupivacaine 2.5 mg kg-1 (0.5 ml kg-1 of 0.5% solution), with or without adrenaline 5 micrograms ml-1, was administered by interpleural injection to 12 patients after elective cholecystectomy. Noncompartmental analysis indicated that the addition of adrenaline had no effect on total body clearance, apparent volume of distribution at steady state or elimination half-life of bupivacaine. However, peak plasma concentrations were lower in the adrenaline group (mean (SD) [range]: 2.57 (0.61) [1.52-3.11] vs 3.22 (0.27) [2.84-3.53] micrograms ml-1, P less than 0.05) and the time to maximum concentration was delayed (median [range]: 25 [15-30] vs 15 [10-20] min, P less than 0.05). Analgesia was variable and no differences were detected between the two groups. The addition of adrenaline appears prudent to minimize possible bupivacaine toxicity.

Analgesia↗

PubMed1990

Pharmacokinetics of propofol in children.

The pharmacokinetics of propofol were studied in 12 healthy Chinese children, aged 4-12 yr, undergoing circumcision under inhalation anaesthesia. All patients received a single i.v. bolus dose of propofol 2.5 mg kg-1 and blood concentrations of propofol over the subsequent 24 h were measured using high pressure liquid chromatography with fluorimetric detection. Data were consistent with a three-compartment model with a mean (SEM) elimination half-life of 209 (29) min and total body clearance of 40.4 (3.6) ml min-1 kg-1. The mean (SEM) apparent volume of distribution at steady state was 5.0 (2.7) litre kg-1 and volume of the central compartment was 0.6 (0.1) litre kg-1. The mean (SEM) ratio of k12:k21 was 1.4 (0.2), suggesting that, after injection of a single bolus dose in children, propofol is distributed rapidly to the shallow compartment. The mean ratio of k31:k10 suggests that lipophilicity constrains return of the drug to the central compartment.

Anesthesia, Inhalation↗

PubMed1990

Distribution of moricizine in human blood: binding to plasma proteins and erythrocytes.

Using equilibrium dialysis and incubation experiments, we determined the binding of moricizine to human plasma, isolated plasma proteins, and erythrocytes. The mean (% +/- SD) plasma protein binding at various moricizine concentrations ranged from 81.2 +/- 2.1 to 89.9 +/- 2.1%. There was no apparent relationship between drug concentration and extent of binding in pooled plasma over the concentration range tested. However, protein concentration-dependent binding was observed with albumin and alpha 1-acid glycoprotein (alpha 1-AGP). The unbound fraction of moricizine fell from 61 to 19% and from 70 to 17% with increasing albumin (5 and 50 g/L, respectively) and alpha 1-AGP (0.2 and 1.2 g/L) concentrations. The binding of moricizine to beta-lipoprotein (5 g/L) was 70.6 +/- 3.1% and to gamma-globulin (12 g/L) was 13.6 +/- 3.3%. Moricizine partitioned into erythrocytes, showing an erythrocyte/plasma drug concentration ratio of 1.325 +/- 0.070 and erythrocyte/buffer ratio of 8.561 +/- 0.620. An estimation could be made that 57% of total drug in whole blood was associated with erythrocytes, 39% bound to plasma proteins, and 4% was free. The results of this study demonstrated that erythrocytes, albumin, and alpha 1-AGP were the major binding components in blood.

Blood Proteins↗

PubMed1990

The two candidate testis-determining Y genes (Zfy-1 and Zfy-2) are differentially expressed in fetal and adult mouse tissues.

The candidate testis-determining Y genes of the mouse Zfy-1 and Zfy-2, encode proteins containing an acidic amino terminus and a carboxyl terminus composed of 13 zinc fingers. The zinc finger domain is conserved among human and mouse zinc finger X and Y genes. We report a 6-amino-acid deletion in the Zfy-2 zinc finger domain of laboratory mice possessing musculus Y chromosomes. The effect of this deletion on the function of Zfy-2 is not known. The reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot techniques were used to study expression of Zfy in adults and fetuses. In adults, the data suggest that Zfy-1 and Zfy-2 transcription is linked to spermatogenesis, that transcription increases with the initiation of meiosis, and that high levels of these mRNAs are found in postmeiotic round spermatid cells. The data also suggest that differential expression of these two genes is present with expression of Zfy-2 being slightly greater than Zfy-1. In fetuses, Zfy transcripts were detected in several tissues, including the testes. In contrast to the situation in adults, the data suggest that expression of Zfy-1 is greater than that of Zfy-2. The data suggesting that Zfy-1 expression is present in fetal testes support the hypothesis that this gene plays a role in testis differentiation. However, because the Zfy genes are apparently also expressed during spermatogenesis and in fetal organs other than testes, they may serve additional functions besides their postulated role in testis determination.

Animals↗

PubMed1990

Role of transesophageal echocardiography in percutaneous balloon mitral valvuloplasty.

Echocardiography is useful in the selection of patients for percutaneous balloon mitral valvuloplasty, which is an effective treatment in suitable patients with rheumatic mitral stenosis. Transesophageal echocardiography appears superior to precordial echocardiography in this role because transesophageal echocardiography is not only reliable in the assessment of mitral valvular morphology but also more sensitive in the detection of left atrial thrombi and mitral regurgitation. Transesophageal echocardiography can be used in guiding the proper positioning of the catheters during the dilatation procedure. Complications of balloon mitral valvuloplasty such as torn mitral leaflets or atrial septal defects can also be diagnosed reliably by transesophageal echocardiography. Thus, transesophageal echocardiography should be an integral part of balloon mitral valvuloplasty.

Catheterization↗

PubMed1990

In vivo evaluation of a dual-action antibacterial, Ro 23-9424, compared to cefotaxime and fleroxacin.

The dual-action antibacterial R 23-9424 (desacetylcefotaxime linked to the quinolone fleroxacin) is a new antibacterial agent with excellent in vitro activity. It was evaluated for in vivo efficacy in comparison with the cephalosporin cefotaxime and the quinolone component, fleroxacin. Ro 23-9424 demonstrated significant activity against all strains tested in systemic infections, including those strains resistant in vivo to cefotaxime (Staphylococcus aureus 753, Serratia marcescens SM and Pseudomonas aeruginosa 8780) and fleroxacin (Streptococcus pneumoniae 6301 and Streptococcus pyogenes. In prophylactic studies, Ro 23-9424 compared favorably with fleroxacin against Escherichia coli and with cefotaxime against S. pyogenes, but Ro 23-9424 was considerably more active than cefotaxime against E. coli and more active than fleroxacin against S. pyogenes. In a murine pneumonia model, Ro 23-9424 was equivalent in activity to cefotaxime against S. pneumoniae and more active than cefotaxime against Klebsiella pneumoniae. Fleroxacin was inactive against S. pneumoniae and about 20-fold more active than Ro 23-9424 against K. pneumoniae. In a murine meningitis infection caused by S. pneumoniae, Ro 23-9424 was 3 times as active as cefotaxime, while fleroxacin was inactive. When meningitis was induced by K. pneumoniae, Ro 23-9424 was as active as the quinolone, while cefotaxime was inactive. In a neutropenic (immunocompromised) model, Ro 23-9424 was more active than cefotaxime against P. aeruginosa and 5-fold less active than fleroxacin. In the control normal (immunocompetent) mouse infection, Ro 23-9424 was 3-fold more active than cefotaxime, but 10-fold less active than fleroxacin.

Animals↗

PubMed1990

Maternal and fetal levels of propofol at caesarean section.

Twenty women were given a bolus induction of propofol 2.0 mg.kg-1 for elective caesarean section. Induction to delivery times ranged from five to fourteen minutes. At delivery the maternal venous (MV) concentrations of propofol ranged from 0.53 to 1.48 micrograms.ml-1 umbilical vein (UV) 0.39 to 1.4 micrograms.ml-1 and umbilical artery (UA) 0.34 to 0.68 micrograms.ml-1 MV propofol concentrations were always higher than corresponding UV concentrations. The mean (95% confidence interval) UV/MV ratio was 0.65 (0.56-0.74) and the mean UA/UV ratio was 1.07 (0.99-1.15). Neither ratio was shown to be correlated with induction to delivery time. Distribution of propofol is rapid across the placenta and in the fetus. Apgar scores were higher with shorter incision to delivery times but were not correlated to umbilical levels of propofol.

Adult↗

PubMed1990

Pharmacokinetics and pharmacodynamics of subcutaneous and intraperitoneal administration of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis.

The single-dose pharmacokinetics of 50 U/kg body weight of recombinant human erythropoietin (rHuEPO) given by either the subcutaneous (s.c.) or the intraperitoneal (i.p.) route were studied in 20 anemic patients maintained on continuous ambulatory peritoneal dialysis. Their baseline hemoglobin levels were less than 9 g/dl. The absorption of rHuEPO via the i.p. route was limited. The serum erythropoietin (EPO) level was only slightly elevated from a baseline value of 27 +/- 3 mU/l to a plateau of 36 +/- 4 mU/l at 12-24 hours. In comparison, after s.c. injection, a peak EPO level of 81 +/- 13 mU/l was obtained after 24 hours. The areas under the concentration-time curve from 0-24 hour were 803 +/- 67 and 1492 +/- 165 mU/l.h for the i.p. and s.c. group respectively (p less than 0.003). The same two groups of patients were then given rHuEPO by either the s.c. or the i.p. route over a period of 16 weeks. In the s.c. group, the hemoglobin increased significantly from 6.9 +/- 0.3 g/dl to 9.8 +/- 0.6 g/dl (p less than 0.004). The mean rHuEPO dosage was 84 +/- 9 U/kg body wt/week. In the i.p. group, despite relatively higher rHuEPO dosage (133 +/- 7 u/kg body wt/week), the hemoglobin level did not increase significantly (7.0 +/- 0.4 g/dl to 8.0 +/- 0.4 g/dl, p = 0.09). Subcutaneous administration of rHuEPO is effective and convenient for patients maintained on continuous ambulatory peritoneal dialysis.

Adult↗

PubMed1990

The measurement of propofol in human blood samples by liquid chromatography.

A simple, sensitive, reliable and rapid column liquid chromatographic method was developed for the measurement of propofol, a new anesthetic agent, in human maternal and placental blood. The assay involved a single extraction of the drug and internal standard, thymol, from blood buffered with 0.1 M sodium dihydrogen phosphate buffer into cyclohexane. The organic extract, basified with tetramethylammonium hydroxide, in evaporation tube was evaporated to dryness at 30 degrees C under nitrogen. The residue was redissolved in 80 microliters acetonitrile and an aliquot (25-50 microliters) of the concentrate was injected into a C18 reversed-phase column (4 microns, Nova-Pak) linked to a C18 pre-column. The mobile phase consisted of 60% (v/v) acetonitrile in distilled water containing 1% v/v glacial acetic acid and was eluted at 2.5 ml min-1. The components of the column effluent was monitored by a fluorometric detector with excitation and emission wavelengths set at 276 nm and 310 nm, respectively. The method has been used to measure propofol concentrations in blood from maternal veins and placental arteries and veins during cesarean section.

Adult↗

PubMed1989

Expression of rat hepatic glucokinase in Escherichia coli.

Rat liver glucokinase was expressed in Escherichia coli by using an expression system based on bacteriophage T7 RNA polymerase. The expressed protein starts with the predicted initiator methionine residue and ends at the appropriate carboxyl terminal residue. It was partially purified by ammonium sulfate precipitation and gel filtration and had kinetic and physical properties similar to the purified rat liver enzyme. The efficient expression of this low abundance hepatic protein in bacteria provides a system for in vitro analysis of mutations of the enzyme.

Base Sequence↗

PubMed1989

Cloning, analysis, and bacterial expression of human farnesyl pyrophosphate synthetase and its regulation in Hep G2 cells.

A partial length cDNA encoding farnesyl pyrophosphate synthetase (hpt807) has been isolated from a human fetal liver cDNA library in lambda gt11. DNA sequence analysis reveals hpt807 is 1115 bp in length and contains an open reading frame coding for 346 amino acids before reaching a stop codon, a polyadenylation addition sequence, and the first 14 residues of a poly(A+) tail. Considerable nucleotide and deduced amino acid sequence homology is observed between hpt807 and previously isolated rat liver cDNAs for farnesyl pyrophosphate synthetase. Comparison with rat cDNAs suggests that hpt807 is about 20 bp short of encoding the initiator methionine of farnesyl pyrophosphate synthetase. The human cDNA was cloned into a prokaryotic expression vector and Escherichia coli strain DH5 alpha F'IQ was transformed. Clones were isolated that express an active fusion protein which can be readily observed on protein gels and specifically stained on immunoblots with an antibody raised against purified chicken farnesyl pyrophosphate phosphate synthetase. These data confirm the identity of hpt807 as encoding farnesyl pyrophosphate synthetase. Slot blot analyses of RNA isolated from Hep G2 cells show that the expression of farnesyl pyrophosphate synthetase mRNA is regulated. Lovastatin increases mRNA levels for farnesyl pyrophosphate synthetase 2.5-fold while mevalonic acid, low-density lipoprotein, and 25-hydroxycholesterol decrease mRNA levels to 40-50% of control values.

Amino Acid Sequence↗

PubMed1989

Steroid metabolism as a mechanism of escape from progesterone-mediated growth inhibition in Trichophyton mentagrophytes.

It has been shown by us and others that progesterone inhibits the growth of Trichophyton mentagrophytes and that the organism escapes from this inhibition over time. We report here studies which show that escape from growth inhibition is related to the enzymatic transformation of progesterone to polar metabolites. Isolation and identification of the progesterone metabolites confirm the production of 15 alpha-hydroxyprogesterone. In addition, three other metabolites were isolated. Two of these were determined to be 1-dehydroprogesterone and 11 alpha-hydroxyprogesterone. The third metabolite was a 1-dehydro-hydroxyprogesterone, but the location of the hydroxyl group could not be determined unequivocally. Studies using authentic 15 alpha-hydroxyprogesterone, 1-dehydroprogesterone, and 11 alpha-hydroxyprogesterone reveal that these derivatives are significantly less inhibitory to the growth of T. mentagrophytes than progesterone. Pretreatment of organisms with progesterone augments the rate of metabolism and enhances escape. We have described previously a progesterone-binding protein (PBP) in cytoplasmic extracts of T. mentagrophytes and hypothesized that progesterone mediates growth inhibition by binding to the PBP of this organism. The relative binding affinity that progesterone and its metabolites display for PBP correlates with the relative growth inhibitory potency of these compounds. These results suggest that metabolism of progesterone to more polar and less inhibitory compounds, which exhibit lower affinity for PBP, is the mechanism of escape from progesterone-mediated inhibition of growth in this organism.

Binding, Competitive↗