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Biomedical subjects

A E Rogers

Publications and source records attributed to A E Rogers.

At least 19 recordsLinked to original sources
PubMed2004

A randomised controlled trial to assess the effectiveness and cost of a patient orientated self management approach to chronic inflammatory bowel disease.

OBJECTIVES: We developed a patient centred approach to chronic disease self management by providing information designed to promote patient choice. We then conducted a randomised controlled trial of the approach in inflammatory bowel disease (IBD) to assess whether it could alter clinical outcome and affect health service use. DESIGN: A multicentre cluster randomised controlled trial. SETTING: The trial was conducted in the outpatient departments of 19 hospitals with randomisation by treatment centre, 10 control sites, and nine intervention sites. For patients at intervention sites, an individual self management plan was negotiated and written information provided. PARTICIPANTS: A total of 700 patients with established inflammatory bowel disease were recruited. MAIN OUTCOME MEASURES: Main outcome measures recorded at one year were: quality of life, health service resource use, and patient satisfaction. Secondary outcomes included measures of enablement-confidence to cope with the condition. RESULTS: One year following the intervention, self managing patients had made fewer hospital visits (difference -1.04 (95% confidence interval (CI) -1.43 to -0.65); p<0.001) without increase in the number of primary care visits, and quality of life was maintained without evidence of anxiety about the programme. The two groups were similar with respect to satisfaction with consultations. Immediately after the initial consultation, those who had undergone self management training reported greater confidence in being able to cope with their condition (difference 0.90 (95% CI 0.12-1.68); p<0.03). CONCLUSIONS: Adoption of this approach for the management of chronic disease such as IBD in the NHS and other managed health care organisations would considerably reduce health provision costs and benefit disease control.

Adaptation, Psychological↗
PubMed2002

Safety assessment of allylalkoxybenzene derivatives used as flavouring substances - methyl eugenol and estragole.

This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavouring substances under conditions of intended use. In this review, scientific data relevant to the safety evaluation of the allylalkoxybenzene derivatives methyl eugenol and estragole is critically evaluated by the FEMA Expert Panel. The hazard determination uses a mechanism-based approach in which production of the hepatotoxic sulfate conjugate of the 1'-hydroxy metabolite is used to interpret the pathological changes observed in different species of laboratory rodents in chronic and subchronic studies. In the risk evaluation, the effect of dose and metabolic activation on the production of the 1'-hydroxy metabolite in humans and laboratory animals is compared to assess the risk to humans from use of methyl eugenol and estragole as naturally occurring components of a traditional diet and as added flavouring substances. Both the qualitative and quantitative aspects of the molecular disposition of methyl eugenol and estragole and their associated toxicological sequelae have been relatively well defined from mammalian studies. Several studies have clearly established that the profiles of metabolism, metabolic activation, and covalent binding are dose dependent and that the relative importance diminishes markedly at low levels of exposure (i.e. these events are not linear with respect to dose). In particular, rodent studies show that these events are minimal probably in the dose range of 1-10 mg/kg body weight, which is approximately 100-1000 times the anticipated human exposure to these substances. For these reasons it is concluded that present exposure to methyl eugenol and estragole resulting from consumption of food, mainly spices and added as such, does not pose a significant cancer risk. Nevertheless, further studies are needed to define both the nature and implications of the dose-response curve in rats at low levels of exposure to methyl eugenol and estragole.

Animals↗
PubMed2001

A comparison of three different sleep schedules for reducing daytime sleepiness in narcolepsy.

STUDY OBJECTIVE: To determine if the combination of scheduled sleep periods and stimulant medications were more effective than stimulant medications alone in controlling the excessive daytime sleepiness experienced by narcoleptic patients. DESIGN: Twenty-nine treated narcoleptic subjects were randomly assigned to one of three treatment groups: 1) two 15-minute naps per day; 2) a regular schedule for nocturnal sleep; or 3) a combination of scheduled naps and regular bedtimes. Measures of symptom severity and unscheduled daytime were obtained at baseline and at the end of the two-week treatment period, using the Narcolepsy Symptom Status Questionnaire (NSSQ) and 24-hour ambulatory polysomnographic monitoring. No alterations were made in stimulant medications during the study period. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The addition of two-15 minute naps did not alter either symptom severity or the duration of unscheduled daytime sleep. Regular times for nocturnal sleep reduced perceived symptom severity, but did not reduce the amount of unscheduled daytime sleep. Only the combination of scheduled naps and regular nocturnal sleep times, significantly reduced both symptom severity and the amount of unscheduled daytime sleep in treated narcoleptic subjects. The type of sleep schedule prescribed, however, was less important than the severity of the patients' pre-treatment daytime sleepiness. Subjects with severe daytime sleepiness benefited from the addition of scheduled sleep periods, while those who were only moderately sleepy or able to maintain alertness did not benefit from scheduled sleep periods. CONCLUSIONS: Scheduled sleep periods are helpful for only those patients who remain profoundly sleepy despite stimulant medications and should not be prescribed for all patients with narcolepsy.

Adult↗
PubMed2001

Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture.

Epidemiological evidence suggests tea (Camellia sinensis L.) has chemopreventive effects against various tumors. Green tea contains many polyphenols, including epigallocatechin-3 gallate (EGCG), which possess anti-oxidant qualities. Reduction of chemically induced mammary gland carcinogenesis by green tea in a carcinogen-induced rat model has been suggested previously, but the results reported were not statistically significant. Here we have tested the effects of green tea on mammary tumorigenesis using the 7,12-dimethylbenz(a)anthracene (DMBA) Sprague-Dawley (S-D) rat model. We report that green tea significantly increased mean latency to first tumor, and reduced tumor burden and number of invasive tumors per tumor-bearing animal; although, it did not affect tumor number in the female rats. Furthermore, we show that proliferation and/or viability of cultured Hs578T and MDA-MB-231 estrogen receptor-negative breast cancer cell lines was reduced by EGCG treatment. Similar negative effects on proliferation were observed with the DMBA-transformed D3-1 cell line. Growth inhibition of Hs578T cells correlated with induction of p27(Kip1) cyclin-dependent kinase inhibitor (CKI) expression. Hs578T cells expressing elevated levels of p27(Kip1) protein due to stable ectopic expression displayed increased G1 arrest. Thus, green tea had significant chemopreventive effects on carcinogen-induced mammary tumorigenesis in female S-D rats. In culture, inhibition of human breast cancer cell proliferation by EGCG was mediated in part via induction of the p27(Kip1) CKI.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Knowledge and communication difficulties for patients with chronic heart failure: qualitative study.

OBJECTIVES: To explore patients' understanding of chronic heart failure; to investigate their need for information and issues concerning communication. DESIGN: Qualitative analysis of in-depth interviews by a constant comparative approach. PARTICIPANTS: 27 patients identified by cardiology and care of the elderly physicians as having symptomatic heart failure (New York Heart Association functional class of II, III, or IV) and who had been admitted to hospital with heart failure in the past 20 months. RESULTS: Participants were aged 38-94 (mean 69 years); 20 had a New York Heart Association classification of III or IV. All had at least one concurrent illness. Participants sought information from the research interviewer about their heart failure, their prognosis, and likely manner of death. They also described several factors that could inhibit successful communication with their doctors. These included difficulties in getting to hospital appointments, confusion, short term memory loss, and the belief that doctors did not want to provide patients with too much knowledge. CONCLUSIONS: Good communication requires the ability both to listen and to impart relevant information. Effective and better ways of communicating with patients with chronic heart failure need to be tested. Disease specific barriers to effective communication, such as short term memory loss, confusion, and fatigue should be addressed. Strategies to help patients ask questions, including those related to prognosis, should be developed.

Adult↗
PubMed2000

Expression of the aryl hydrocarbon receptor/transcription factor (AhR) and AhR-regulated CYP1 gene transcripts in a rat model of mammary tumorigenesis.

Exposure to ubiquitous environmental chemicals, such as polycyclic aromatic hydrocarbons (PAH), may contribute to human breast cancer. In animals, PAH induce tumors in part by activating the aryl hydrocarbon receptor (AhR)/transcription factor. Historically, investigations into AhR-regulated carcinogenesis have focused on AhR-dependent transcriptional regulation of cytochrome P450 (CYP) enzymes which oxidize PAH to mutagenic intermediates. However, recent studies suggest that the AhR directly regulates cell growth. Given the postulated role of the AhR in carcinogenesis, we predicted that: (1) tissue predisposed to PAH tumorigenesis would express the AhR and (2) aberrant AhR and/or AhR-regulated gene expression would accompany malignant transformation. To test these hypotheses, AhR and CYP1 protein and/or mRNA levels were evaluated in rat mammary tumors induced with 7, 12-dimethylbenz[a]anthracene (DMBA), a prototypic PAH and AhR ligand. Results indicate modest AhR expression in normal mammary myoepithelial and ductal epithelial cells. In contrast, high AhR levels were detected in DMBA-induced tumors. Nuclear AhR localization in tumors suggested constitutive AhR activation. In situ hybridization and quantitative RT-PCR assays indicated high AhR mRNA levels in neoplastic epithelial cells. While both AhR-regulated CYP1A1 and CYP1B1 mRNAs were induced in breast tissue within 6 h of DMBA gavage, only CYP1B1 mRNA remained elevated in tumors. These results: (1) help explain targeting of breast tissue by carcinogenic PAH, (2) imply that AhR and CYP1B1 hyper-expression represent molecular biomarkers for, at least, PAH-induced mammary cell transformation, and (3) suggest mechanisms through which the AhR may contribute to carcinogenesis well after exogenous AhR ligands have been eliminated.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Activation of NF-kappaB/Rel occurs early during neoplastic transformation of mammary cells.

NF-kappaB/Rel is a family of transcription factors which are expressed in all cells; however, in most non-B cells, they are sequestered in the cytoplasm in inactive complexes with specific inhibitory proteins, termed IkappaBs. We have recently shown that NF-kappaB/Rel factors are aberrantly activated in human breast cancer and rodent mammary tumors, and function to promote tumor cell survival and proliferation. Here, we have examined the time-course of induction of NF-kappaB/Rel factors upon carcinogen treatment of female Sprague-Dawley (S-D) rats in vivo and in human mammary epithelial cells (HMECs) in culture. We observed that NF-kappaB/Rel activation is an early event, occurring prior to malignant transformation. In S-D rats, increased NF-kappaB/Rel binding was detected in nuclear extracts of mammary glands from 40% of animals 3 weeks post-treatment with 15 mg/kg 7,12-dimethylbenz[a]anthracene (DMBA); this is prior to formation of tumors which normally begin to be detected after 7-9 weeks. In non-tumorigenic MCF-10F cells, in vitro malignant transformation upon treatment with either DMBA or benzo[a]pyrene (B[a]P) resulted in a 4- to 12-fold increase in activity of classical NF-kappaB (p65/p50). NF-kappaB induction was corrrelated with a decrease in the stability of the NF-kappaB-specific inhibitory protein IkappaB-alpha. Ectopic expression of the transactivating p65 subunit of NF-kappaB in MCF-10F cells induced the c-myc oncogene promoter, which is driven by two NF-kappaB elements, and endogenous c-Myc levels. Furthermore, reduction mammoplasty-derived HMECs, immortalized following B[a]P exposure, showed dysregulated induction of classical NF-kappaB prior to malignant transformation. Together these findings suggest that activation of NF-kappaB plays an early, critical role in the carcinogen-driven transformation of mammary glands.

Animals↗
PubMed1999

Health-related quality of life effects of modafinil for treatment of narcolepsy.

OBJECTIVE: To evaluate the burden of illness of narcolepsy and assess the health-related quality-of-life (HQL) effects of oral modafinil, a wake-promoting therapy for excessive daytime sleepiness associated with narcolepsy. METHODS: Subjects with narcolepsy enrolled in a nine-week, placebo-controlled, double-blind study and were randomized to placebo, modafinil 200 mg, or modafinil 400 mg. After the study, consenting subjects received modafinil in a 40-week open-label extension. A self-administered HQL questionnaire consisting of the 36-Item Short Form Health Survey (SF-36) and supplemental narcolepsy-specific scales was given to subjects at baseline, study endpoint, and several open-label timepoints. RESULTS: 481 subjects completed a baseline and double-blind endpoint HQL assessment. Compared to population norms, baseline HQL scores reflected substantial burden in vitality, social functioning, and performing usual activities. At study endpoint, subjects in the 400 mg modafinil group had significantly higher scores than placebo for 10 of the 17 HQL scales. The 400 mg modafinil group had more energy, fewer difficulties performing usual activities, fewer interferences with social activities, improved psychological well-being and higher productivity, attention and self-esteem compared to placebo subjects (p<.05). The positive treatment effects were sustained over the open-label extension. CONCLUSION: Modafinil significantly improves health-related quality of life in narcolepsy.

Adult↗
PubMed1999

Dietary fat, body weight, and cancer: contributions of studies in rodents to understanding these cancer risk factors in humans.

Understanding diet and energy balance as risk factors for breast, colon, and other cancers requires information on the contribution of each factor and of interactions among factors to cancer risk. Rodent models for breast cancer provide extensive data on effects of dietary fat and calories, energy balance, body weight gain, and physical activity on tumor development. Analyses of the combined data from many studies have shown clearly that quality and quantity of dietary fat and energy balance contribute independently to increased mammary gland tumorigenesis. These findings were seen in female rats fed diets high in fat (35-40% of calories) compared to rats fed control diets, with approximately 10% of calories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46, 215-223). The methods used permit comparison of experimental and epidemiological data, and they may be useful in extrapolating between species and developing public health recommendations. In addition to the contributions of lifetime-diet composition, intake, energy balance, and physical activity to cancer risk, there are questions about the timing and duration of alterations in these factors and about the "dose-response" characteristics of cancer risk to the factors. Endocrine mechanisms may be significant in mammary gland tumor risk, but experimental and epidemiological data indicate that cancers at other sites, such as colon and liver, also are influenced by the factors listed. Other diet and lifestyle factors that influence energy, or specifically fat, metabolism may also affect risk for cancers that are promoted by increased intake of fat and calories. Studies of separate and interactive effects of dietary fat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, et al, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Using adjustment of carcinogenesis endpoints for body weight, tumor burden, and latency, they were found to be related to weight gain within treatment groups in 2 of 3 experiments.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Black tea and mammary gland carcinogenesis by 7,12-dimethylbenz[a]anthracene in rats fed control or high fat diets.

Epidemiological studies suggest that tea may reduce cancer risk, and in laboratory rodents, chemopreventive effects of tea or purified extracts of tea have been demonstrated in lung, gastrointestinal tract and skin. There is some evidence of chemoprevention by tea in the mammary gland, but the data are not conclusive. In order to evaluate more fully the possible influence of black tea on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary gland tumors in the female S-D (Sprague-Dawley) rat, three large studies were performed: experiment 1, tumorigenesis in rats fed AIN-76A diet and given 25 mg/kg DMBA and 1.25 or 2.5% whole tea extract or water to drink; experiment 2, tumorigenesis in rats given 15 mg/kg DMBA and the same diet and fluids as in experiment 1; experiment 3, tumorigenesis in rats fed control or HF (high fat, corn oil) diet and given 15 mg/kg DMBA and 2% tea or water to drink. Tea was given throughout the experiment; DMBA was given by gastric gavage at 8 weeks of age. There was no consistent effect of tea on tumorigenesis in rats fed AIN-76A diet; there was, however, evidence in experiment 3 of a reduction of tumorigenesis by tea in rats fed the HF diet. In experiment 3, rats fed the HF diet and given water showed the expected increase in tumor burden (number and weight) compared with rats fed control diet. However, rats fed the HF diet and given 2% tea showed no increase in tumor burden; their tumor burden was significantly lower than in rats fed the HF diet and given water (P < 0.01) and was not different from rats fed control diet and given water or tea. In addition, in experiment 3, the number of malignant tumors per tumor-bearing rat was increased by the HF diet in water-drinking rats (P < 0.01) but not in tea-drinking rats. Therefore, it appears that tea partially blocked the promotion of DMBA-induced mammary tumorigenesis by the HF diet.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer.

Expression of nuclear factor-kappaB (NF-kappaB)/Rel transcription factors has recently been found to promote cell survival, inhibiting the induction of apoptosis. In most cells other than B lymphocytes, NF-kappaB/Rel is inactive, sequestered in the cytoplasm. For example, nuclear extracts from two human untransformed breast epithelial cell lines expressed only very low levels of NF-kappaB. Unexpectedly, nuclear extracts from two human breast tumor cell lines displayed significant levels of NF-kappaB/Rel. Direct inhibition of this NF-kappaB/ Rel activity in breast cancer cells induced apoptosis. High levels of NF-kappaB/Rel binding were also observed in carcinogen-induced primary rat mammary tumors, whereas only expectedly low levels were seen in normal rat mammary glands. Furthermore, multiple human breast cancer specimens contained significant levels of nuclear NF-kappaB/Rel subunits. Thus, aberrant nuclear expression of NF-kappaB/Rel is associated with breast cancer. Given the role of NF-kappaB/Rel factors in cell survival, this aberrant activity may play a role in tumor progression, and represents a possible therapeutic target in the treatment of these tumors.

9,10-Dimethyl-1,2-benzanthracene↗