Biomedical subjects

G Tucker

Publications and source records attributed to G Tucker.

At least 19 recordsLinked to original sources

PubMed2000

The SF-36 summary scales: problems and solutions.

To determine the accuracy of the SF-36 summary mental and physical health scales in reflecting their underlying subscales using the traditional method of scoring based on factor coefficients derived through principle components analysis and orthogonal rotation. A representative Australian population survey containing the SF-36 was used to obtain factor coefficients from principle components analysis and orthogonal rotation for scoring the physical component summary (PCS) and the mental component summary (MCS) of the SF-36 in the traditional way. In addition two other methods were used to produce coefficients. The first method used maximum likelihood extraction and oblique rotation. The second method fit a structural equation model to the data in a confirmatory factor analysis. The coefficients derived by each of the methods were applied to the data of a second representative population survey. This survey also provided data on physical and mental health status which allowed comparison of the summary scores and underlying subscales according to various health states. Neither of the scoring methods based on the exploratory factor analyses methods (orthogonal and oblique) produced summary scale scores, by age group, that adequately reflected the underlying subscales. When coefficients derived using structural equation modeling were fit to the data in a confirmatory factor analysis the MCS and PCS accurately reflected their underlying subscale scores. They also produced MCS and PCS scores for the various health states as would be expected from the underlying subscales. The traditional methods of scoring the SF-36 summary scales produce results that would not be expected from the underlying subscales. The problem was only corrected by fitting a structural equation model to the data in a confirmatory factor analysis. The results advise caution in the use of the SF-36 summary scales and suggests that alternative methods of developing factor coefficients need to be employed in studies using the SF-36 summary scales.

Adolescent↗

PubMed2000

Population-based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility.

AIMS: There is evidence that plasma methadone measurements may be of benefit in dosage adjustment during methadone maintenance treatment for opiate dependence. However, to date the kinetics of oral rac-methadone have been poorly characterized. We describe plasma methadone concentration-time data collected from 35 opiate addicts. SUBJECTS: Oral doses of rac-methadone were given to 24 male and 11 female addicts attending a community-based drug treatment centre. MEASUREMENTS: Plasma methadone concentrations were measured by liquid chromatography (HPLC). PROCEDURES: Plasma concentration-time data were collected from patients prescribed oral rac-methadone in order to describe the complex kinetics of the drug incorporating its long elimination half-life. FINDINGS: Auto-induction of methadone metabolism was demonstrated and it was observed that clearance of methadone was significantly lower (p < 0.05) in opiate addicts at the start of treatment (median elimination half-life, 128-hours) than in those who had reached steady-state (median elimination half-life, 48 hours). Our data has provided the basis for a population-based pharmacokinetic (POP-PK) model which is intended for use as a clinical tool in association with plasma measurements in methadone maintenance patients. CONCLUSIONS: Using plasma monitoring in combination with the application of Bayesian forecasting it should be possible to predict trough levels of methadone during daily dosing. The model is able to utilize sparse sampling, and two blood samples are expected to be sufficient to define patient compliance. Random samples during treatment could be used to assess methadone dosing by comparing predicted with observed measurements for each individual. The clinical tool could therefore help to detect incomplete (failure to consume the whole daily dose as prescribed) and poor (due to ingestion of extra illicit methadone) compliance as well as therapeutic failure due to drug-drug interactions. Targeting resources in this way could be a cost-effective tool for supervision of methadone dosing.

Administration, Oral↗

PubMed1999

Tumour suppressive properties of fibroblast growth factor receptor 2-IIIb in human bladder cancer.

FGFRs (fibroblast growth factor receptors) are encoded by four genes (FGFR1-4). Alternative splicing results in various receptor isoforms. The FGFR2-IIIb variant is present in a wide variety of epithelia, including the bladder epithelium. Recently, we have shown that FGFR2-IIIb is downregulated in a subset of transitional cell carcinomas of the bladder, and that this downregulation is associated with a poor prognosis. We investigated possible tumour suppressive properties of FGFR2-IIIb by transfecting two human bladder tumour cell lines, J82 and T24, which have no endogenous FGFR2-IIIb expression, with FGFR2-IIIb cDNA. No stable clones expressing FGFR2-IIIb were isolated with the J82 cell line. For the T24 cell line, stable transfectants expressing FGFR2-IIIb had reduced growth in vitro and formed fewer tumours in nude mice which, in addition, grew more slowly. The potential mechanisms leading to decreased FGFR2-IIIb mRNA levels were also investigated. The 5' region of the human FGFR2 gene was isolated and found to contain a CpG island which was partially methylated in more than half the cell lines and tumours which do not express FGFR2-IIIb. No homozygous deletion was identified in any of the tumours or cell lines with reduced levels of FGFR2-IIIb. Mutational analysis of the entire coding region of FGFR2-IIIb at the transcript level was performed in 33 bladder tumours. In addition to normal FGFR2-IIIb mRNA, abnormal transcripts were detected in two tumour samples. These abnormal mRNAs resulted from exon skipping which affected the region encoding the kinase domain. Altogether, these results show that FGFR2-IIIb has tumour growth suppressive properties in bladder carcinomas and suggest possible mechanisms of FGFR2 gene inactivation.

Animals↗

PubMed1999

Demonstration of the capabilities of a parallel high performance liquid chromatography tandem mass spectrometry system for use in the analysis of drug discovery plasma samples.

There is a continuing need for increased throughput in the evaluation of new drug entities in terms of their pharmacokinetic (PK) parameters. This report describes an alternative procedure for increasing the throughput of plasma samples assayed in one overnight analysis: the use of parallel high performance liquid chromatography (HPLC) combined with tandem mass spectrometry (parallel LC/MS/MS). For this work, two HPLC systems were linked so that their combined effluent flowed into one tandem MS system. The parallel HPLC/APCI-MS/MS system consisted of two Waters 2690 Alliance systems (each one included an HPLC pump and an autosampler) and one Finnigan TSQ 7000 triple quadrupole mass spectrometer. Therefore, the simultaneous chromatographic separation of the plasma samples was carried out in parallel on two HPLC systems. The MS data system was able to deconvolute the data to calculate the results for the samples. Using this system, 20 compounds were tested in one overnight assay using the rapid rat PK screening model which includes a total of 10 standards plus samples and two solvent blanks per compound tested. This application provides an additional means of increasing throughput in the drug discovery PK assay arena; using this approach a two-fold increase in throughput can be achieved in the assay part of the drug discovery rat PK screening step.

Animals↗

PubMed1999

Validation of the pneumonia severity index. Importance of study-specific recalibration.

OBJECTIVE: To evaluate the predictive validity and calibration of the pneumonia severity-of-illness index (PSI) in patients with community-acquired pneumonia (CAP). PATIENTS: Randomly selected patients (n = 1,024) admitted with CAP to 22 community hospitals. MEASUREMENTS AND MAIN RESULTS: Medical records were abstracted to obtain prognostic information used in the PSI. The discriminatory ability of the PSI to identify patients who died and the calibration of the PSI across deciles of risk were determined. The PSI discriminates well between patients with high risk of death and those with a lower risk. In contrast, calibration of the PSI was poor, and the PSI predicted about 2.4 times more deaths than actually occurred in our population of patients with CAP. CONCLUSIONS: We found that the PSI had good discriminatory ability. The original PSI overestimated absolute risk of death in our population. We describe a simple approach to recalibration, which corrected the overestimation in our population. Recalibration may be needed when transporting this prediction rule across populations.

Adult↗

PubMed1999

The epidemiology of hearing impairment in an Australian adult population.

BACKGROUND: This study measured the prevalence of hearing impairment, and major demographic factors that influence the prevalence, in a representative South Australian adult population sample aged > or = 15 years. METHODS: The study group was recruited from representative population surveys of South Australians. Participants in these surveys who reported a hearing disability were then recruited to an audiological study which measured air and bone conduction thresholds. In addition a sample of those people who reported no hearing disability were recruited to the audiological study. RESULTS: The data reported in this study are the first in Australia to assess the prevalence of hearing impairment from a representative population survey using audiological methods. The data show that 16.6% of the South Australian population have a hearing impairment in the better ear at > or = 25 dBHTL and 22.2% in the worse ear at the same level. The results obtained in this representative sample compare well with those obtained in the British Study of Hearing, although some differences were observed. CONCLUSIONS: Overall, there are only a few studies worldwide that have audiologically assessed the impairment of hearing from a representative population sample. The overall prevalence of hearing impairment in Australia is similar to that found in Great Britain, although there are some differences between the estimates of severity of impairment and some sex differences. The corroboration of the two studies reinforces the status of hearing impairment as the most common disability of adulthood. The present study also showed that there are a large number of Australians who may benefit from a more systematic community-based rehabilitation programme including the fitting of hearing aids. Secondly, the study identified the need for health goals and targets for hearing to be based on an epidemiological approach to the problem.

Adolescent↗

PubMed1999