Biomedical subjects

Judith Brown

Publications and source records attributed to Judith Brown.

10 recordsLinked to original sources

PubMed2006

Return to work after ill-health retirement in Scottish NHS staff and teachers.

BACKGROUND: Most major public and private sector pension schemes have provision for ill-health retirement (IHR) for those who become too ill to continue to work before their normal retirement age. AIM: To compare the causes, process and outcomes of IHR in teachers and National Health Service (NHS) staff in Scotland. METHODS: A total of 537 teachers and 863 NHS staff who retired due to ill-health between April 1998 and March 2000 were mailed an IHR questionnaire by the Scottish Public Pensions Agency. RESULTS: The response rate for teachers was 53% and for NHS staff 49%. The most common cause of IHR was musculoskeletal disorders for NHS staff and mental disorders for teachers. Teachers retired at a younger average age than NHS staff. Ninety-two per cent of NHS staff but only 11% of teachers attended occupational health services (OHS) prior to IHR. Eighteen per cent of NHS staff and 9% of teachers were offered part-time work by their current employer in response to their ill-health. Fifteen per cent of NHS staff and 5% of teachers were offered alternative work prior to retirement. Seventeen per cent of NHS staff and 36% of teachers subsequently found employment. Multiple logistic regression analyses showed the following variables as independent predictors of subsequent employment: occupational group, age group, sex, managerial responsibility and cause of IHR. CONCLUSIONS: Return to work after IHR suggests that some IHR could be avoided. Teachers had a higher rate of return to work and much less access to OHS.

Age Distribution↗

PubMed2006

Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers.

High breast density as measured on mammograms is a strong risk factor for breast cancer in the general population, but its effect in carriers of germline BRCA1 and BRCA2 mutations is unclear. We obtained mammograms from 206 female carriers of BRCA1 or BRCA2 mutations, 96 of whom were subsequently diagnosed with breast cancer and 136 relatives of carriers who were themselves noncarriers. We compared the mammographic densities of affected carriers (cases) and unaffected carriers (controls), and of mutation carriers and noncarriers, using a computer-assisted method of measurement and visual assessment by two observers. Analyses were adjusted for age, parity, body mass index, menopausal status, and hormone replacement therapy use. There was no difference in the mean percent density between noncarriers and carriers. Among carriers, increasing mammographic density was associated with an increased risk of breast cancer (P(trend) = 0.024). The odds ratio (OR; 95% confidence interval) for breast cancer associated with a density of > or =50% was 2.29 (1.23-4.26; P = 0.009). The OR did not differ between BRCA1 and BRCA2 carriers or between premenopausal and postmenopausal carriers. The results suggest that the distribution of breast density in BRCA1 and BRCA2 carriers is similar to that in non-carriers. High breast density in carriers is associated with an increased risk of breast cancer, with the relative risk being similar to that observed in the general population. Use of mammographic density could improve individual risk prediction in carriers.

Adult↗

PubMed2005

Ill health retirement in Scottish teachers: process, outcomes and re-employment.

OBJECTIVES: To assess the process, causes and outcomes of ill health retirement (IHR) in teachers in Scotland. Perceptions and experience of occupational health services (OHS), access to rehabilitation and redeployment, current health, post retirement experience and predictors of re-employment were identified. METHODS: 537 teachers who retired due to ill health between April 1998 and March 2000 were mailed our IHR questionnaire by the Scottish Public Pensions Agency. RESULTS: The most common cause of IHR was mental disorders (37%), followed by diseases of the musculoskeletal system (18%). 11% of teachers attended an OHS prior to IHR. 9% of teachers were offered part-time work and 5% were offered alternative work. 63% of retired teachers stated their health had improved and 48% said they would like to work again. 36% of the surveyed teachers have found re-employment since their retirement. On unadjusted analyses, re-employment of teachers after IHR was significantly associated with sex, having dependants, job group, cause of IHR, health having improved and wanting to work again. Multiple logistic regression analyses showed three variables as independent predictors of re-employment: having dependants, job group and cause of IHR. CONCLUSION: This is the first comprehensive study investigating teachers' experiences of IHR in Scotland. The findings highlight substantial lack of support for teachers in a number of areas which need to be addressed by managers and employers. Our study confirms the need for rehabilitation and teacher support services in order to try and retain experienced teachers in the profession.

Adult↗

PubMed2005

The involvement of occupational health services prior to ill-health retirement in NHS staff in Scotland and predictors of re-employment.

OBJECTIVE: To assess the process, causes and outcomes of retirement because of ill-health in NHS staff in Scotland. Particular areas to be investigated include the involvement of occupational health services, access to rehabilitation and redeployment, current health, whether working again and to identify predictors of re-employment. METHOD: An ill-health retirement (IHR) questionnaire was mailed to 863 NHS staff awarded IHR benefits by the Scottish Public Pensions Agency between April 1998 and March 2000. RESULTS: In all, 49% of the 863 postal questionnaires were returned. The most common reasons for retiring were diseases of the musculoskeletal system (38%) and mental disorders (21%). Seventy-one percent of the participants reported their ill-health was partly or completely work related and 29% not work related. Ninety-two percent of NHS staff had attended an occupational health department prior to IHR. Twenty-three percent of participants had no contact with their line manager during their illness prior to retiral. Eighteen percent of individuals were offered the opportunity of working part-time and 15% offered alternative work. Seventeen percent of participants have obtained other work. Predictors of re-employment after IHR were: medical condition, managerial responsibility, improvement of health, wanting to work again, occupation and age at retirement. CONCLUSION: This is the first comprehensive study investigating NHS staff experiences of IHR in Scotland. This study illustrates the need for improved support and rehabilitation for ill-health care workers and that there is the potential to reduce levels of ill-health retirement.

Adult↗

PubMed2003

Effects of dietary flavonoids on major signal transduction pathways in human epithelial cells.

Flavonoids (FVs) are an important class of plant compounds postulated to be one of the constituents responsible for the beneficial effects of fruits and vegetables on health, including heart disease and cancer. At pharmacological levels, various naturally-occurring flavonoids have been shown to be cancer-protective in a variety of animal models and flavonoid derivatives, such as flavopyridol, are being assessed as chemotherapy drugs in clinical trials. This report has investigated the effects of the most common dietary FVs on several major signalling pathways in biopsies of human epithelial cells using primary cultures freshly isolated from biopsies and has obtained evidence for the previously unrecognised importance of stress kinase responses induced by kaempferol (KF), apigenin (AP) and luteolin (LU). KF, AP and LU all activated ATM/ATR (mutated in ataxia-telangiectasia and related) kinases and the p38 stress kinase and this was associated with induction of GADD45 and cell cycle arrest in G2, but not induction of apoptosis. These effects were not due to general toxicity since they were reversible on removal of FV. The inductions of ATM/ATR and p38 were functionally important since caffeine, an inhibitor of ATM/ATR, and the p38-specific inhibitor, SB203580, prevented induction of GADD45 and growth arrest by these three flavonoids. In contrast, although quercetin (QU) activated ATM (but not ATR), it did not activate p38 kinase, GADD45 or p53. QU may interfere with one of the lipoxygenase (LOX) pathways since the growth inhibitory effects of QU (but not the other three flavonoids) could be reversed by addition of LOX metabolites, particularly 12- and 15-hydroxyeicostetraenic acids.

Cell Cycle↗

PubMed2003

Enhanced sensitivity of human oral tumours to the flavonol, morin, during cancer progression: involvement of the Akt and stress kinase pathways.

Various naturally occurring flavonoids have been found to be cancer-protective in chemically induced animal cancer models and synthetic flavonoid derivatives are being tested for potential chemotherapeutic usefulness in clinical trials. This report demonstrates that human oral squamous carcinoma cells (SCC) are significantly more sensitive to growth inhibition by the naturally occurring flavonoid, morin (3,5,7,2',4'-pentahydroxyflavone) than normal oral mucosa (NOMC) (SCC IC(50) = 115 microM; NOMC IC(50) = 173 micro M; P for difference = 0.009). Structure/function comparisons indicate that both the 2' and 4' hydroxyl groups in morin are required for its tumour selectivity. Morin causes growth arrest in G(2)/M, without inducing apoptosis, and this is associated with induction of GADD45 and phosphorylation and inactivation of the cell cycle kinase, cdc2. Morin also has pleiotropic effects on kinase signalling pathways, including inhibition of activation of protein kinase B by mitogens (but not extracellular-regulated kinases 1/2) and activation of the stress pathway kinases, Jun N-terminal kinase and p38 kinase. p38 kinase activation is functionally important since inhibition of its activation by the specific inhibitor SB202190 partially prevented cell cycle arrest by morin. However, analysis of dose-response relationships reveals that the enhanced tumour sensitivity to morin may be explained by the fact that activation of AKT is inhibited at lower concentrations of morin in carcinomas than normal oral mucosa, whereas Jun N-terminal kinase, p38 kinase and GADD45 are all induced in parallel with the same dose-response curves in carcinomas and normal oral mucosa.

3T3 Cells↗

PubMed2003

A good death in rural Kenya? Listening to Meru patients and their families talk about care needs at the end of life.

What constitutes a good death sub-Saharan Africa? In Meru District in Eastern Kenya, we listened to 32 patients with ongoing cancer or AIDS, and to their carers as they talked about end-of-life experiences and care needs. Patients described how the support of close family relationships, and the care shown by their community and religious fellowships helped meet many of their emotional, social, and spiritual needs. But physical needs often went unmet. Patients died in pain. Some suffered in poverty, others were troubled by the guilt of using all available family resources to pay for treatment and care. Accessible pain relief, affordable clinic or inpatient care when required, and help to cope with the burden of care were among the key needs of patients. Until these are available, many will not die well.

Adolescent↗

PubMed2002

Enhanced drug dissolution using evaporative precipitation into aqueous solution.

A new process, evaporative precipitation into aqueous solution (EPAS) has been developed to coat poorly water soluble drugs, in this case carbamazepine, with hydrophilic stabilizers to enhance dissolution rates. A heated organic solution of the drug in dichloromethane is sprayed though a fine nozzle into a heated aqueous solution. The rapid evaporation of the organic solvent produces high supersaturation and rapid precipitation of the drug in the form of a colloidal suspension that is stabilized by a variety of low molecular weight and polymeric surfactants. The stabilizer adsorbs to the drug surface and prevents particle growth and crystallization during the spray process. The suspensions are dried by spray drying or ultra-rapid freezing. The high dissolution rates are a consequence of the following advantages of the EPAS process: a small primary particle size, a hydrophilic coating on the particles that enhances wetting, and low crystallinity.

Anticonvulsants↗

PubMed2002

Molecular changes associated with oral dysplasia progression and acquisition of immortality: potential for its reversal by 5-azacytidine.

This study has identified molecular changes characteristic of early oral cancer progression. We reported previously that acquisition of the immortal phenotype is an early event in oral cancer development (F. McGregor et al., Cancer Res., 57: 3886-3889, 1997); our current data indicate that about half of oral dysplasia cultures are immortal, and this is associated with loss of expression of retinoic acid receptor (RAR)-beta and the cell cycle inhibitor p16(ink4a) (p16), p53 mutations, and increased levels of telomerase/human telomerase reverse transcriptase mRNA. In contrast, increased expression of the epidermal growth factor receptor, known to be a characteristic of oral cancer, does not occur until after the dysplasia stage in squamous cell carcinomas. Acquisition of invasive properties as judged by an in vitro Matrigel invasion assay also does not occur until the carcinoma stage and is further increased in metastases. Interestingly, one atypical mortal dysplasia with a considerably extended life span has lost expression of RAR-beta and p16, but it still expresses only wild-type p53 (albeit at a higher level than normal) and has not activated telomerase. RAR-beta and/or p16 re-expression can be induced by treatment with 5-aza-2-deoxycytidine (Aza-C) in some immortal dysplasias, and this has been shown to be due to silencing of gene expression by promoter methylation. Aza-C treatment also down-regulated telomerase activity and human telomerase reverse transcriptase mRNA. Interestingly, with one dysplasia, Aza-C was able to reverse its immortal phenotype, as judged by morphological criteria and expression of the senescence-associated acid beta-galactosidase activity during terminal growth arrest; this immortal dysplasia was the only one in which Aza-C treatment not only down-regulated telomerase activity but also induced re-expression of both RAR-beta and p16. The possibility of reversing the immortal phenotype of some dysplasias by Aza-C may be of clinical usefulness.

Antimetabolites, Antineoplastic↗

PubMed2002

Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology.

PURPOSE: To develop and demonstrate a novel particle engineering technology, spray freezing into liquid (SFL), to enhance the dissolution rates of poorly water-soluble active pharmaceutical ingredients (APIs). METHODS: Model APIs, danazol or carbamazepine with or without excipients, were dissolved in a tetrahydrofuran/water cosolvent system and atomized through a nozzle beneath the surface of liquid nitrogen to produce small frozen droplets, which were subsequently lyophilized. The physicochemical properties of the SFL powders and controls were characterized by X-ray diffraction, scanning electron microscopy (SEM), particle size distribution, surface area analysis, contact angle measurement, and dissolution. RESULTS: The X-ray diffraction pattern indicated that SFL powders containing either danazol or carbamazepine were amorphous. SEM micrographs indicated that SFL particles were highly porous. The mean particle diameter of SFL carbamazepine/SLS powder was about 7 microm. The surface area of SFL danazol/poloxamer 407 powder was 11.04 m2/g. The dissolution of SFL danazol/poloxamer 407 powder at 10 min was about 99%. The SFL powders were free flowing and had good physical and chemical stability after being stored at 25 degrees C/60%RH for 2 months. CONCLUSIONS: The novel SFL technology was demonstrated to produce nanostructured amorphous highly porous particles of poorly water soluble APIs with significantly enhanced wetting and dissolution rates.

Drug Compounding↗