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Biomedical subjects

G Tucker

Publications and source records attributed to G Tucker.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

Introduction.

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Journal Article↗

Introduction.

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Journal Article↗

Language of dysfunction in schizophrenia.

Twenty-four medicated schizophrenic subjects participated in a study aimed at assessing language dysfunction in schizophrenia. Two groups of subjects participated: schizophrenic responders and non-responders to treatment with antipsychotic medication. All subjects were tested on The Western Aphasia Battery test (WAB), the Cookie Theft picture descriptions task, and the Wechsler Adult Intelligence Scales--Revised (WAIS-R) block design and picture arrangement subtests. All verbal and non-verbal assessments were compared between groups. The three main findings of this study were: 1. Severe language of dysfunction among schizophrenic patients who do not respond to medication treatment. That is, therapeutic response to medication was the major predictor of the severity of language dysfunction in schizophrenia. 2. A group profile of language dysfunction differed in severity but not in shape between responders and non-responders to treatment with antipsychotic medication. 3. Schizophrenic responders and non-responders to medication treatment did not differ in their performance on a standardised picture description task and failed to reach low-moderate aphasia level. Secondary findings suggest that non-verbal aspects, such as attention and logical sequencing, may be influenced by treatment. This study represents an assessment of schizophrenic language function in relation to known language deficits of neurological patients, lending further support for the role of central nervous system (CNS) dysfunction in schizophrenia, and the importance of assessing language dysfunction as a sensitive gauge to treatment response.

Adolescent↗

Cost-effective inpatient care of neuropsychiatric patients.

Managed care has decreased the frequency of hospitalization for psychiatric disorders, and it may have an especially strong impact on neuropsychiatric patients. The use of targeted, cost-effective interventions improves the quality of patient care and can assist with approval of funding for inpatient care by utilization review agencies.

Cost-Benefit Analysis↗

Medical and narrative approaches in psychiatry.

Using a case example, the authors contrast two different approaches to psychiatric assessment: the medical approach, in which the physician examines signs and symptoms and compares them with diagnostic criteria for various disorders, and the narrative approach, in which the clinician tries to understand symptoms as a part of a meaningful story and as understandable responses to external conditions. Both approaches make essential contributions to psychiatry. The current conflict between biological psychiatry and psychotherapeutic psychiatry can be seen as a result of reductionist polarization involving these opposite approaches. The reconciliation of these opposites may be vital for the survival of general psychiatry as a medical specialty.

Adult↗