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Biomedical subjects

K Fielding

Publications and source records attributed to K Fielding.

24 records · Page 2Linked to original sources

Scatter factor/hepatocyte growth factor expression enhances human glioblastoma tumorigenicity and growth.

We have shown previously that the multifunctional cytokine scatter factor/hepatocyte growth factor (SF/HGF) is elevated in human malignant gliomas. In this study we investigated how human SF/HGF expression affects the malignancy of the U373 human glioblastoma cell line in vivo and in vitro. Human SF/HGF gene transfer increased U373 glioblastoma tumorigenicity by > or = 20-fold and enhanced the growth rate of intracerebral U373 xenografts by 3- to 8-fold. SF/HGF expression had no effect on the proliferation of glioblastoma cell monolayers but increased their anchorage-independent colony formation in soft agar by 5- to 8-fold. These results are the first to show that SF/HGF expression by human glioblastoma cells enhances their growth dysregulation in vitro and malignancy in vivo.

Animals↗

The effect of deprivation on variations in general practitioners' referral rates: a cross sectional study of computerised data on new medical and surgical outpatient referrals in Nottinghamshire.

OBJECTIVE: To determine the effect of deprivation on variations in general practitioners' referral rates using the Jarman underprivileged area (UPA(8)) score as a proxy measure. DESIGN: Cross sectional survey of new medical and surgical referrals from general practices to hospitals (determined from hospital activity data). SETTING: All of the 183 general practices in Nottinghamshire and all of the 19 hospitals in Trent region. MAIN OUTCOME MEASURES: The relation between the referral rates per 1000 registered patients and the practice population's UPA(8) score (calculated on the basis of electoral ward), with adjustment for the number of partners, percentage of patients aged over 65 years, and fundholding status of each practice. RESULTS: There was a significant independent association between deprivation, as measured by the UPA(8) score, and high total referral rates and high medical referral rates (P < 0.0001). The UPA(8) score alone explained 23% of the total variation in total referral rates and 32% of the variation in medical referral rates. On multivariate analysis, where partnership size, fundholding status, and percentage of men and women aged over 65 years were included, the UPA(8) score explained 29% and 35% of the variation in total and medical referral rates respectively. CONCLUSION: Of the variables studied, the UPA(8) score was the strongest predictor of variations in referral rates. This association is most likely to be through a link with morbidity, although it could reflect differences in patients' perceptions, doctors' behaviour, or the use and provision of services.

England↗

Pituitary dysfunction in recently post-menopausal women. Nottingham EPIC Study Group.

OBJECTIVE: Some recently post-menopausal women have lower than expected FSH concentrations, raising the possibility of subclinical hypothalamo-pituitary impairment. We have therefore performed pituitary stimulation tests in a group of recently post-menopausal women recruited to a bone loss prevention study. DESIGN: Prospective study of health volunteers. SETTING: Outpatient, teaching hospital in Nottingham UK. SUBJECTS: Forty-seven women selected from a cohort of 428 healthy volunteers to an osteoporosis prevention study all within 10 years of the menopause. MAIN OUTCOME MEASURES: Response of the pituitary to formal stimulation tests and its relationship to bone mineral density. RESULTS: A significantly attenuated response to pituitary stimulation was found in a group of otherwise healthy women with an FSH considered to be inappropriately low for the level of circulating oestradiol. The impaired responses were significant not only for FSH as expected but also to LH and prolactin at 1 hour after injection of GnRH and TRH (area under the curve, FSH P = 0.01, LH P = 0.001, prolactin P < 0.0001). TSH secretion was not significantly impaired. Baseline cortisol, growth hormone and thyroxine (T4) were normal in both control and test subjects. The test group was both heavier and taller, with a higher lean body mass, a higher body mass index and a greater total body fat than the controls. Bone mineral density showed no significant differences between the groups. Test subjects also had a higher free oestradiol index (P < 0.001) which correlated strongly (r = 0.534, P = 0.00026) with baseline FSH levels and possibly reflects a greater tissue exposure to biologically active hormone. Oestrone concentrations were, however, no different between the groups. CONCLUSIONS: Serum FSH concentrations are not invariably elevated in recently post-menopausal women and use of FSH as a determinant for postmenopausal status in clinical trials should be used with caution. Notwithstanding their higher free oestradiol index, women found to have an abnormally low basal FSH had evidence of poor prolactin, FSH and LH but not TSH responses to pituitary stimulation. This may represent either a degree of subclinical pituitary failure of a variant of normal. The low levels of gonadotrophin activity did not affect bone mineral density.

Bone Density↗

Are patients who present late with cancer registered with low referring practices?

This study examines whether a clinical outcome (stage of breast or bowel cancer at referral) was related to variations in GP referral rates. A multivariate analysis of breast and bowel cancer patients referred from 183 Nottinghamshire practices during 1993 showed no adverse outcome associated with low GP referral rates. Variables included in the analysis were total and surgical referral rates, fundholding status, UPA(8) score of the practice, partnership size, and age and sex of the referred patient.

Breast Neoplasms↗

Reliability and accuracy of the Glasgow Coma Scale with experienced and inexperienced users.

To investigate whether the Glasgow Coma Scale (GCS) can be used reliably and accurately by inexperienced observers, ratings made by observers grouped by level of experience were examined for within-group interobserver disagreements and for discrepancies with scores given by an expert. The GCS was used accurately by experienced and highly trained users, but inexperienced users made consistent errors. The errors were such that they would not be detectable by studies that examine only interobserver agreement, and they were substantial, averaging in some cases more than one point on the four-point and five-point scales of the GCS. Also, the error rates were highest at the intermediate levels of consciousness, for which the detection of changes in condition is vital. The findings support the continued use of the GCS by appropriately qualified personnel, but call into question much of the conventional wisdom about its reliability when used by untrained or inexperienced staff. The findings also suggest that interobserver comparisons are insufficient for establishing the viability of the GCS.

Evaluation Studies as Topic↗

Reliability of assessments by skilled observers using the Glasgow Coma Scale.

The management of patients at risk of neurological deterioration is often centred around serial assessments made by nursing and medical clinicians using the Glasgow Coma Scale. Although accepted throughout the world as a reliable and consistent tool for such assessments, little work has been done to validate the original claims of reliability. In this study a very high degree of inter-rater reliability was demonstrated between registered nurses (RNs) who were educated and experienced in use of the scale. Implications for clinical practice are discussed.

Coma↗