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Biomedical subjects

R C Li

Publications and source records attributed to R C Li.

At least 55 records · Page 3Linked to original sources
PubMed1997

Efficient assay for the determination of atenolol in human plasma and urine by high-performance liquid chromatography with fluorescence detection.

An efficient method for the determination of atenolol in human plasma and urine was developed and validated. alpha-Hydroxymetoprolol, a compound with a similar polarity to atenolol, was used as the internal standard in the present high-performance liquid chromatographic analysis with fluorescence detection. The assay was validated for the concentration range of 2 to 5000 ng/ml in plasma and 1 to 20 microg/ml in urine. For both plasma and urine, the lower limit of detection was 1 ng/ml. The intra-day and inter-day variabilities for plasma samples at 40 and 900 ng/ml, and urine samples at 9.5 microg/ml were <3% (n=5).

Adrenergic beta-Antagonists↗
PubMed1997

Expression and prognostic value of proliferating cell nuclear antigen in transitional cell carcinoma of the urinary bladder.

Forty-eight patients with transitional cell carcinima (TCC) of the bladder were investigated. Routine paraffin-embedded sections were stained with proliferating cell nuclear antigen (PCNA) monoclonal antibody in order to determine the growth fraction of the bladder tumors and to correlate this with tumor grade, stage, development of recurrence and survival rate during follow-up. PCNA positive staining was detected in 95.8% (46/48) of the tumors. The mean labeling index (LI) of superficial tumors (Ta-1, n = 28) was 12.58 +/- 12.33%, and 34.55 +/- 21.89% in invasive tumors (T2-4, n = 18). A similar correlation was found in association with tumor grade. The patients were followed up for a mean of 4.9 years (range 1-14 years). The mean PCNA LI in nonrecurrent (n = 21) and simple recurrent (n = 7) superficial tumors was 11.29 +/- 11.79% and 16.44 +/- 14.05%, respectively, the difference not being statistically significant. To access survival, tumors with a PCNA LI above and below the median level (21%) were compared. Those patients (n = 19) with an index of > 21% (the mean of all the PCNA values) had a worse prognosis than those (n = 27) with an index of < 21%, a difference which is statistically significant. These results suggest that PCNA LI in bladder cancer may prove to be an objective and quantitative assay of biological aggressiveness and provide significant prognostic information, although it does not help the selection of patients at risk of simple recurrence in superficial tumors.

Adult↗
PubMed1997

The chirality selectivity in the uptake of platinum (II) complexes with 1,2-cyclohexanediamine isomers as carrier ligand by human erythrocytes.

The uptake kinetics of cisplatin analogs of 1,2-cyclohexanediamine(dach) isomers with various leaving groups, by human erythrocytes in plasma isotonic buffer, were studied. The experimental results showed that the uptake rate constants (k values) decrease with the change of leaving group in the sequence: chloride (Cl) > squaric acid (SA) > oxalate (OX) > demethylcantharic acid (DA), with the same dach isomer as carrier group. It is noteworthy that for the platinum (II) complexes with the same leaving group, the k values always reduce as: 1R, 2R-dach > 1R, 2S-dach > 1S, 2S-dach. This result reflects the chirality selectivity. No differences in reactivity to protein thiols and effects on membrane permeability were found for the R,R-, R,S-, S,S-isomeric complexes. It is proposed that the chirality selectivity in uptake is due to the recognition of the chirality of the platinum complexes by the erythrocyte membrane. The interactions between the chiral platinum complexes and the head groups of the membrane phospholipid molecules are probably involved.

Cell Membrane Permeability↗
PubMed1997

Correlation between bactericidal activity and postantibiotic effect for five antibiotics with different mechanisms of action.

Theoretically, if the postantibiotic effect (PAE) reflects the duration of cellular recovery, then the extent of cellular damage inflicted on bacteria by an antibiotic, as suggested by the degree of bactericidal activity, should reflect the length of PAE; this is especially true if binding of the antibiotic to bacterial receptors is irreversible. To test this hypothesis, correlation between PAEs and bactericidal rate constants measured simultaneously at various antibiotic concentrations was examined for five antibiotic-bacterium combinations. Each of the five antibiotics used, i.e. tobramycin, ciprofloxacin, dicloxacillin, trimethoprim and tetracycline, has a different mechanism of action: the first three bind irreversibly to bacterial receptors, while trimethoprim and tetracycline bind reversibly. Both PAE and bactericidal activity increased nonlinearly with concentrations in a saturable manner for all the combinations studied. Linear least-square regression analyses showed strong correlations (P < 0.01) between the two responses for individual combinations. Such a linear relationship also extended, with good correlation (P < 0.05), across the five combinations when individual maximal bactericidal rate constants and PAEs were considered separately. These observations suggest that cellular recovery from nonlethal damage following antibiotic exposure may be a major determinant of PAE.

Anti-Bacterial Agents↗
PubMed1997

Expanded version of PKSIM for pharmacokinetic simulations of both metabolite and parent drugs.

We recently described a computer software package for pharmacokinetic simulations called PKSIM. The programs are useful for studying drugs that display either a one-, two-, or three-compartment body model with linear or nonlinear elimination following single or multiple dosing. The practicality of PKSIM owes to its user-friendliness and flexibility to study the impact of pharmacokinetic perturbations and dosage regimens on the drug's concentration-time profile on a real-time basis. The interactive nature of PKSIM allows the test variables to be easily changed after each simulation. High-resolution graphic capabilities also permit presentation of pharmacokinetic profile in various body compartments, either individually or collectively on a single graph. The capability of PKSIM was recently extended to include simulations of both parent drug and metabolite, which adds to the value of the package. The present paper describes in detail the functions of these new features and how they can be applied to better comprehend the pharmacokinetic interdependency between the parent drug and metabolite. In addition to the dose, dosing regimen and rate of drug absorption, influences on the kinetic profiles of parent drug and metabolite by other variables such as formation rate of the metabolite, tissue distribution, tissue redistribution, elimination rates and distribution volume of both entities can be studied with minimal efforts. These new features can be particularly helpful for researchers to study prodrugs and drugs that produce active or toxic metabolites, or better understand the basic concepts of metabolite kinetics.

Biotransformation↗
PubMed1997

Rifabutin absorption in the gut unaltered by concomitant administration of didanosine in AIDS patients.

Didanosine (ddI) is currently used in the management of patients infected by the human immunodeficiency virus. Rifabutin (RBT) is being extensively used for prophylaxis against Mycobacterium avium complex (MAC) infections. Due to its acid-labile characteristics, ddI must be administered with a buffer. Recent reports have indicated that absorption of ketoconazole, ciprofloxacin, and dapsone, etc., in the gut is altered by concomitant ddI dosing. We have assessed whether concomitant dosing of ddI as antiretroviral therapy modifies RBT absorption in the gut, its steady-state pharmacokinetics, and/or safety in 15 patients with AIDS. Of the 15 patients enrolled, 12 completed the study and 3 receiving 600 mg of RBT with concomitant ddI administration withdrew prematurely from the study. Steady-state RBT pharmacokinetics were assessed on day 13 (ddI plus RBT) and day 16 (RBT alone). The ddI doses (adjusted for body weight) were 167 to 375 mg twice daily, while RBT was administered as a single 300- or 600-mg daily dose. No statistically significant (P > 0.05) differences were seen in RBT absorption parameter estimates between days 13 and 16: maximum concentration in plasma (Cmax; 511 +/- 341 ng/ml versus 525 +/- 254 ng/ml) and the time at which Cmax was observed (3.0 versus 2.5 h). The mean RBT estimates for area under the concentration-time curve from 0 to 24 h (AUC(0-tau)) (5,650 versus 5,023 ng x h/ml) and for oral clearance (1.28 versus 1.18 liter/h/kg) on both study days were also similar. Assessment based on urinary recovery of RBT (3.1 versus 3.7 mg) and its predominant deacetyl metabolite, LM565 (1.6 versus 1.4 mg), showed no apparent effect of ddI. The fraction of the RBT dose converted to LM565, as suggested by the ratio of AUC of the metabolite to AUC of the parent drug, was also unaltered (0.15 versus 0.12). A ratio analysis (day 13/day 16) of the RBT pharmacokinetic estimates showed that the 95% confidence intervals for all parameters were inclusive of one. Furthermore, the brief interruption of ddI therapy over this short study period at steady state produced no clinically significant changes in body weight, hematology, and renal and pancreatic functions. Therefore, concomitant administration of ddI appears not to affect RBT absorption in the gut and its disposition or safety in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Antibiotic exposure and its relationship to postantibiotic effect and bactericidal activity: constant versus exponentially decreasing tobramycin concentrations against Pseudomonas aeruginosa.

In vitro postantibiotic effects (PAEs) exhibited by a standard strain of Pseudomonas aeruginosa following exposure to tobramycin at constant concentrations were compared to those at exponentially decreasing concentrations. Exposure to a constant concentration showed more extensive bacterial killing and resulted in longer PAEs at comparable areas under the concentration-time curves above the MIC. This phenomenon suggests a significant contribution of pharmacokinetics to antimicrobial pharmacodynamics.

Anti-Bacterial Agents↗
PubMed1997

Relationship between isokinetic concentric and eccentric contraction modes in the knee flexor and extensor muscle groups.

We investigated whether in normal subjects isokinetic concentric and eccentric strength variables were related in order to have a better picture in relation to rehabilitation and possible injury prevention. We studied the relationship between isokinetic concentric and eccentric peak torque, total work, and average power of knee extension and knee flexion at 60 degrees/sec and 120 degrees/sec in 42 young Chinese adults (22 males, age = 27 +/- 6.9 years; 20 females, age = 24.9 +/- 5.05 years) using the Cybex 6000 isokinetic dynamometer. Repeated analysis of covariance was used to compare the means between concentric and eccentric variables adjusted by limb dominance, speed of testing, and the muscle groups tested. A highly significant correlation was found between all concentric and eccentric variables, with correlation coefficients (r) ranging from 0.67 to 0.93. All but two of the eccentric variables were significantly greater than the concentric variables. Concentric and eccentric knee flexion to knee extension (H:Q) ratios were poorly correlated, with r ranging from 0.359 to 0.645. Although there is an acceptably high correlation between isokinetic concentric and eccentric strength variables of knee flexion and extension in young healthy individuals, we recommend measuring concentric and eccentric strength to plan a proper rehabilitation program and to assess muscle groups in a given contraction mode.

Adult↗
PubMed1997

In vitro models for prediction of antimicrobial activity: a pharmacokinetic and pharmacodynamic perspective.

The endpoints associated with conventional susceptibility testing, e.g., the minimum inhibitory concentration or minimum bactericidal concentration (MIC or MBC), are discrete in nature. These endpoint measurements do not provide any information, regarding the pharmacodynamic changes exhibited by the bacteria in reaction to the antibiotic activity during the incubation period. Another limitation of these susceptibility tests is the maintenance of constant antibiotic concentrations; this condition contrasts sharply to the continuously changing concentrations observed in vivo. To tackle these problems, various in vitro pharmacokinetic/pharmacodynamic models have been developed. Taking into consideration various pharmacokinetic determinants, such models allow more comprehensive study of the pharmacodynamic effects demonstrated by antibiotics. In this paper, the implications and usefulness of these in vitro models to the characterization of antimicrobial activity are discussed. Limitations associated with their use are also addressed.

Anti-Bacterial Agents↗
PubMed1996

A model based assessment of redistribution dependent elimination and bioavailability of rifabutin.

The autoinduction characteristic of rifabutin (RIF) following multiple oral dosing was investigated via pharmacokinetic modeling. A two-compartment model with first-order absorption was fit to plasma RIF data obtained from a study conducted in healthy normal volunteers following both a single and multiple oral doses. Parameter estimates showed an elimination rate constant (k10) of about 0.12-0.14 h-1 which was independent of the single or multiple-dosing condition. The lower-than-expected drug accumulation following multiple dosing seems to suggest that prolonged dosing perturbs the linear kinetic system. However, this analysis has shown no significant changes (p > 0.05) in the rate constants describing RIF absorption, tissue distribution/redistribution, and elimination. The mean rate of drug redistribution from the tissue compartment (k21; 0.04-0.06 h-1) was twofold to threefold lower than k10, and, with a large steady-state distribution volume (Vss/F after a single dose, 1630 L), RIF elimination appears to be dependent on drug redistribution. This hypothesis was further supported by a significant correlation (p < 0.01) between RIF tissue redistribution (k21) and terminal disposition phase rate (lambda z) constants. The redistribution dependent elimination of RIF also helps explain the stability of the terminal half-life under both single and multiple-dosing paradigms. Urinary excretion of RIF and its 25-O-deacetyl metabolite totalled less than 7% of the oral dose following single dosing, and decreased to about 4% after multiple dosing. For individual patients, the decrease in urinary recovery of the 25-O-deacetyl metabolite was directly proportional to the decrease in urinary RIF recovery. In addition, both estimates of the model intercepts (A and B) were lower following multiple dosing. Further analyses revealed a linear relationship between A and B intercepts, and also between the urinary RIF recovery and the B intercept. These relationships, in conjunction with the lack of significant increase in the rate of elimination, indicate that induction of presystemic extrahepatic metabolism and/or decrease in the extent of oral absorption may be the primary causes for the lower-than-expected systemic RIF plasma levels after multiple oral dosing.

Administration, Oral↗
PubMed1996

Simultaneous pharmacodynamic analysis of the lag and bactericidal phases exhibited by beta-lactams against Escherichia coli.

Antibiotic-bacterium interactions are complex in nature. In many cases, bacterial killing does not commence immediately after the addition of an antibiotic, and a lag period is observed. Antibiotic permeation and/or the intermediate steps that exist between antibiotic-receptor binding and expression of cell death are two major possible causes for such lag period. This study was primarily designed to determine the relationship, if any, between antibiotic concentrations and the lag periods by a modeling approach. Short-term time-kill studies were conducted for amoxicillin, ampicillin, penicillin-G, oxacillin, and dicloxacillin against Escherichia coli. In conjunction with the use of a saturable rate model to describe the concentration-dependent killing process, a first-order induction (initiation) rate constant was used to characterize the delay in bacterial killing during the lag period. For all of the beta-lactams tested, parameters describing the bactericidal effect suggest that amoxicillin and ampicillin were much more potent than oxacillin and dicloxacillin. The induction rate constant estimates for both ampicillin and amoxicillin were found to relate linearly to concentrations. Nevertheless, these induction rate constant estimates were lower for penicillin-G, oxacillin, and dicloxacillin and increased nonlinearly with concentrations until an apparent plateau was observed. These findings support the hypothesis that the permeation process is potentially a rate-limiting step for the rapid bactericidal beta-lactams such as ampicillin and amoxicillin. However, as suggested by previous observations of the various morphological changes induced by beta-lactams, the contribution of the steps following antibiotic-receptor complex formation to the lag period might be significant for the less bactericidal antibiotics such as oxacillin and dicloxacillin. Findings from the present modeling approach can potentially be used to guide future bench experimentation.

Anti-Bacterial Agents↗
PubMed1996

Lack of effect of concomitant zidovudine on rifabutin kinetics in patients with AIDS-related complex.

The effect of concomitant dosing with the antiretroviral agent zidovudine (ZDV) on the pharmacokinetics of rifabutin (RBT) was investigated under steady-state conditions. Sixteen human immunodeficiency virus-positive patients with AIDS-related complex who had been maintained on stable ZDV therapy for > or = 6 weeks were administered RBT concomitantly for 12 days. Eight patients received daily doses of 300 or 450 mg of RBT. Administration of ZDV was discontinued on day 13, and RBT was given alone for 3 additional days. Four patients receiving 450 mg of RBT discontinued treatment. Under steady-state ZDV and RBT dosing, safety and kinetics assessments were performed on day 13 (ZDV plus RBT) and day 16 (RBT alone). Kinetics on days 13 and 16 demonstrated that RBT (300 or 450 mg) was readily absorbed, with the time at which the plasma concentration was maximal (Tmax) ranging between 2.6 and 2.9 h. At these two doses, the mean steady-state maximal plasma concentrations (Cmax) were 250 and 430 ng/ml on day 13 and 245 and 458 ng/ml on day 16, respectively. RBT kinetics at the two doses were proportional and similar on the basis of estimates of the ratios of the areas under the concentration-time curves over the dosing interval from 0 to 24 h (AUC0-24) (450 mg/300 mg), which were 1.5 and 1.4 for days 13 and 16, respectively. No significant differences were apparent in the mean oral clearance (CLs/F) estimates (range, 1.60 to 1.77 liters/h/kg), which were dose independent and similar for the 2 assessment days, as was the urinary recovery of RBT and its 25-deacetyl metabolite. Low urinary recovery of 25-deacetyl RBT and an AUC metabolite/parent ratio of 0.1 suggest that there is minimal metabolism of RBT via the deacetylation pathway. For RBT, pooled mean (95% confidence interval) ratio (day 13/day 16) estimates for Cmax, Tmax, AUC0-24, and CLs/F were 1.07 (range, 0.77 to 1.38), 1.08 (0.89 to 1.27), 0.97 (0.82 to 1.13), and 1.09 (0.92 to 1.26), respectively. In addition, no significant changes in any of the major safety parameters were detected throughout the study. Therefore, it is concluded that coadministration of ZDV and RBT does not affect the pharmacokinetics and/or safety of RBT in human immunodeficiency virus-positive patients.

AIDS-Related Complex↗
PubMed1996

Novel method for assessing postantibiotic effect by using the Coulter counter.

To study postantibiotic effect, viable counts are routinely acquired by the pour plate technique. However, this technique is laborious and time-consuming; the required sample dilutions also cause excessive errors and material wastage. A new total cell counting technique in which a Coulter counter is used to obtain more efficient postantibiotic effect measurements has been developed.

Anti-Bacterial Agents↗
PubMed1996

Eccentric and concentric isokinetic knee flexion and extension: a reliability study using the Cybex 6000 dynamometer.

OBJECTIVE: To determine the reliability of the Cybex 6000 isokinetic dynamometer in measuring the knee muscle performance concentrically and eccentrically. METHODS: 18 male and 12 female subjects with no previous knee injuries, who had not previously undergone any isokinetic testing, were studied. The flexor and extensor muscles groups of both knees were tested at 60 degrees s-1 and 120 degrees s-1 with the continuous concentric-eccentric cycle testing protocol. Variables studied included peak torque, total work, and average power. The interclass correlation coefficient (ICC 2,1) was used to determine the reliability with P < 0.05. RESULTS: Peak torque showed significantly greater ICC than the total work and average power, with test-retest reliability ranging from 0.82 to 0.91 for peak torque, from 0.76 to 0.89 for total work, and 0.71 to 0.88 for average power. Average variability for the three variables studied ranged from 9% to 14%. The ICCs for the three variables studied were significantly greater at 120 degrees s-1. The knee extensor muscle group showed greater test-retest reliability, and the results of isokinetic testing in the concentric contraction mode were more reproducible. CONCLUSIONS: The Cybex 6000 isokinetic dynamometer shows high reliability in measuring isokinetic concentric and eccentric variables. Some fluctuation should be allowed when evaluating variations of muscle performance between tests.

Adult↗
PubMed1996

Isokinetic strength of the quadriceps and hamstrings and functional ability of anterior cruciate deficient knees in recreational athletes.

OBJECTIVE: To test the hypothesis that increasing the hamstrings and quadriceps (H:Q) isokinetic strength ratio will, in the short term, improve the functional ability of an anterior cruciate ligament (ACL) deficient knee. METHODS: The isokinetic muscular characteristics at a speed of 60 degrees s-1 and 180 degrees s-1 of 46 recreational athletes with an arthroscopically confirmed ACL tear were determined using the Cybex II+ isokinetic dynamometer. The variables tested included peak torque, endurance ratio, total work output, and explosive power. Functional ability was scored with the Cincinnati rating system, measuring the severity of pain and swelling, the degree of giving way, and the overall ability to walk, run, ascent and descent stairs, jump and twist. RESULTS: Among all muscular characteristics, the H:Q ratio at 180 degrees s-1 at 30 degrees of knee flexion was shown to have the highest correlation to the functional score (r = 0.6249, P < 0.001). All variables involving hamstring strength were shown to be significantly correlated to the functional ability score (P < 0.01), while none of the variables involving quadriceps strength showed significant correlation with the functional ability of the injured knee. CONCLUSIONS: The H:Q ratio is strongly correlated to the functional ability of ACL deficient knees in Chinese recreational athletes. It could be used as an additional measure to guide in the decision making process in the management of ACL deficient knees.

Adult↗
PubMed1996

Performance of the fractional maximal effect method: comparative interaction studies of ciprofloxacin and protein synthesis inhibitors.

The performance of the recently developed Fractional Maximal Effect (FME) method was evaluated along with the conventional checkerboard technique and time-kill method. Ciprofloxacin in combination with tobramycin was tested against Escherichia coli and Pseudomonas aeruginosa and in combination with tetracycline, chloramphenicol, erythromycin against Escherichia coli. Two combinations, amoxicillin-tetracycline (antagonistic) and tobramycin-ticarcillin (synergistic), were included as reference interactions. The FME method unequivocally showed an antagonistic interaction between ciprofloxacin and all the protein synthesis inhibitors (PSIs) tested, while the other two methods yielded variable results. At a total FME (TFME) level of 1, the FME method demonstrated a similar degree of antagonism against ciprofloxacin by tetracycline, chloramphenicol, and erythromycin, and much lower by tobramycin. Internal consistency of the FME operation was demonstrated by the identical conclusions obtained at both TFME levels of 0.5 and 1. The FME method appears to be a practical alternative for resolving the inconsistencies observed in conventional methods of antibiotic combination testing.

Anti-Infective Agents↗