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Biomedical subjects

R Clarke

Publications and source records attributed to R Clarke.

At least 109 records · Page 6Linked to original sources
PubMed1997

Who is a heavy service user? Preliminary development of a screening instrument for prospective consumers of a mobile intensive treatment team.

OBJECTIVE: The mobile intensive treatment team (MITT) of the Valley Integrated Adult Mental Health Service in Brisbane, Australia, aims to provide services in the community to people with severe and persistent mental illness who have traditionally been heavily reliant on inpatient services (i.e. heavy service users). The MITT screening instrument (MITTSI) was developed to provide an objective measure to appropriately identify patients for referral to the service. METHOD: A literature review and a panel of multidisciplinary clinicians were consulted to identify a list of specific attributes that would assist in the detection of heavy service users. These attributes were then formulated into an easy-to-administer screening instrument entitled the MITTSI. The MITTSI was administered in an interview format to MITT case managers (intensive case management) and to case managers in standard case management with prospective MITT patients (prospective heavy service users). RESULTS: Analyses of the responses indicated support for the MITTSI as a valid screening instrument in identifying heavy service users and for determining appropriate patients for referral to the MITT. CONCLUSION: The MITTSI is an easy-to-administer screening instrument which provides clear guidelines for inclusion and exclusion, and is an objective measure regarding the patients' urgency for referral to the MITT. Follow-up of the MITTSI within a broader, longer-term project will attempt to further refine the MITTSI and to further determine its validity. Outcomes will be published at a later stage.

Adult↗
PubMed1997

Isolation of environmental mycobacteria from clinical specimens in south-east England: 1973-1993.

SETTING: A reference centre for tuberculosis bacteriology serving South-East England. OBJECTIVE: The number of cultures of environmental mycobacteria (EM) submitted to regional and reference laboratories in the UK is increasing, and is adding considerably to the workload of these laboratories. The changing trends in the numbers and nature of EM submitted to the Dulwich Public Health Laboratory Regional Tuberculosis Centre (RTC), have been analysed to establish the nature of the increase. DESIGN: This study is based on all cultures of EM submitted to RTC between 1973 and 1993. The cultures were grouped according to year of first isolation, number of isolates and data supplied by the client laboratories, including age and human immunodeficiency virus (HIV) status of the patients and the anatomical sites from which the mycobacteria were isolated. RESULTS: A total of 9379 EM from 6668 patients was received. Single and multiple isolates were received, respectively, from 4681 and 1192 patients not known to be HIV positive and from 477 and 318 who were known to be HIV positive. The annual number of patients not known to be HIV positive with isolates of probable clinical significance increased steadily from less than 40 in 1973 to over 100 per year since 1990. Isolates of doubtful clinical significance also showed an increase over time. The annual numbers from HIV positive patients increased steeply following the first such isolates in 1984. CONCLUSIONS: The data show that the annual number of isolates of EM from both HIV positive and negative patients is increasing both absolutely and relatively to isolates of Mycobacterium tuberculosis. This trend should be considered when planning the future scope and activities of mycobacterium reference laboratories, including the introduction of new DNA-based diagnostic methods.

Body Fluids↗
PubMed1996

Breast cancer risk in rats fed a diet high in n-6 polyunsaturated fatty acids during pregnancy.

BACKGROUND: Women who took the synthetic estrogen diethylstilbestrol during pregnancy exhibit an elevated risk of breast cancer, whereas those who suffered from preeclampsia, which is associated with low circulating pregnancy estrogens, exhibit a reduced risk. Since a high-fat diet may increase circulating estrogen levels and possibly breast cancer risk, dietary factors during pregnancy could influence the risk of developing this disease. PURPOSE: We tested the hypothesis that consumption of a high-fat diet during pregnancy increases carcinogen-induced mammary tumor incidence in rats. METHODS: Pregnant or virgin female Sprague-Dawley rats that had been previously treated with 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA) by oral gavage when 55 days old were assigned to one of two isocaloric diets containing either 16% calories from fat (low-fat) or 43% calories from fat (high-fat) for the length of pregnancy or for the equivalent time of approximately 21 days. There were 20 pregnant and 10 nonpregnant DMBA-treated rats per group. Ten additional pregnant animals (not previously treated with DMBA) per group were used for hormone analysis. The fat source used was corn oil, which is high in n-6 polyunsaturated fatty acids, primarily linoleic acid. The animals were checked for tumors at least once per week by palpation. The tumor size, number, and latency to appearance after carcinogen exposure were recorded. The statistical significance of observed differences was tested by use of appropriate two-sided tests. RESULTS: Female rats on different diets had virtually identical food intakes and weight gains during pregnancy. On gestation day 19, serum estradiol levels were approximately twofold higher in rats fed a high-fat diet than in rats fed a low-fat diet (P < .02). The serum insulin levels and insulin/glucose ratios (an index of insulin resistance) in rats fed the high-fat diet were approximately twofold lower than in rats fed the low-fat diet, but the differences did not reach statistical significance (P < .09 and P < .09, respectively). On week 18 following DMBA administration, the number of rats developing mammary tumors was significantly higher in the group exposed to a high-fat diet (40% of animals) than in the group exposed to a low-fat diet (10% of animals) during pregnancy (P < .05). Tumor multiplicity, latency to tumor appearance, and size of tumors upon first detection were similar among the dietary groups. No intergroup differences in the mammary tumor incidence were noted in virgin animals that were exposed to the high- or low-fat diets for an equivalent period of time. CONCLUSIONS: Our findings indicate that consumption of a diet high in fat (primarily in the form of n-6 polyunsaturated fatty acids) during pregnancy increases the risk of developing carcinogen-induced mammary tumors, possibly by increasing the pregnancy levels of circulating estrogens. IMPLICATIONS: If further studies find that the results from animal model studies are applicable to humans, some human breast cancers may be preventable by dietary manipulations during pregnancy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Animal models of breast cancer: their diversity and role in biomedical research.

Animal models of breast cancer have been widely used to study various aspects of breast cancer biology, and are remarkably diverse, encompassing chemically and virally induced tumors, human tumor xenografts, and transgenic mouse models. Several novel models have become available during the past few years, including tumors induced by polyomavirus and adenovirus, and a series of human cell line variants. The several following articles describe, in some detail, the characteristics of these models and their relevance to the human disease. Descriptions of each of the major models, e.g., 7,12-dimethylbenz(a)anthracene-induced, MMTV-associated, and human breast cancer cell line xenografts, also are included. The limitations and advantages of several of these models, and some issues relating to the choice of models, are briefly discussed in this overview.

Animal Welfare↗
PubMed1996

Human breast cancer cell line xenografts as models of breast cancer. The immunobiologies of recipient mice and the characteristics of several tumorigenic cell lines.

The ability to maintain and study human tissues in an in vivo environment has proved to be a valuable tool in breast cancer research for several decades. The most widely studied tissues have been xenografts of established human breast cancer cell lines into athymic nude mice. Human breast tumor xenografts provide the opportunity to study various important interactions between the tumor and host tissues, including endocrinologic, immunologic, and tumor-stroma interactions. The nude mouse is not the only immune-deficient recipient system in which to study xenografts. Additional single and combined mutant strains have been used successfully, including mice homozygous for the severe combined immune deficiency mutation (scid), both the beige (bg) and nude (nu) mutations in combination (bg/nu), and mice bearing the combined bg/nu/xid mutations. The differing immunobiologies are discussed, with particular reference to the immunobiology of breast cancer, as are the characteristics of several of the more frequently utilized breast cancer xenografts and cell lines. The ability of several endocrine treatments to modulate effectors of cell mediated immunity, e.g., estrogens and antiestrogens, and the effect of site of inoculation on tumor take and metastasis, also are described.

Animals↗
PubMed1996

Effects of short-term antiestrogen treatment of primary breast cancer on estrogen receptor mRNA and protein expression and on estrogen-regulated genes.

Effects of the pure antiestrogen ICI182780 and tamoxifen on ER-protein, ER-mRNA, and estrogen-regulated mRNA expression were analysed using matched pretreatment core-cut biopsies and post-treatment mastectomy samples from 43 ER positive human breast cancers. Sixteen controls received either no preoperative treatment (n = 9) (7 days) or placebo (n = 7) (median 21 days) prior to primary surgery. Nineteen patients received ICI182780 6 mg/day (n = 10) or 18 mg/day (n = 9) for 7 days. Eight patients were given preoperative tamoxifen (4 x 40 mg-day 1, 20 mg/day thereafter, median 21 days). ER-protein expression was assessed on pre and post treatment samples by immunocytochemistry. ER, pS2, pLIV1, and actin-mRNA expression was determined by northern analysis on post-treatment samples only. ER-mRNA levels were similar to controls following ICI182780 or tamoxifen treatment. However ER-protein levels were significantly suppressed by ICI182780, particularly at the higher dosage (p = 0.0013). Tamoxifen had no significant effect on ER-protein levels. The ER-mRNA and ER-protein contents of control tumors were linearly related (Spearman r = 0.719, p = 0.006). A similar relationship between pretreatment protein and post ICI182780 treatment mRNA levels was observed (r = 0.652, p = 0.005). However, comparison of post ICI182780 treatment protein and mRNA results shows a loss of linearity through a reduction in protein without concurrent loss of mRNA (r = 0.28, p = 0.257). pS2 mRNA hybridization was lower in ICI182780 treated samples than controls (Mann-Whitney p = 0.035) but was unaffected by tamoxifen. pLIV1 mRNA hybridization was uninfluenced by either treatment. Short term exposure of breast tumors to ICI182780 appears to produce a greater inhibition of estrogen-induced transcriptional events than tamoxifen. These effects appear to occur without a concurrent reduction in ER mRNA levels.

Antineoplastic Agents, Hormonal↗
PubMed1996

Specific binding of estradiol to rat coronary artery smooth muscle cells.

We report the expression and characteristics of the estrogen receptor in rat coronary artery-derived smooth muscle cells. Polymerase chain reaction analyses of total and poly(A) + mRNA from rat coronary artery-derived smooth muscle cells indicate the presence of estrogen receptor mRNA. Binding analyses reveal the presence of high affinity binding sites for 17 beta-estradiol, with a Kd equivalent to that observed for authentic estrogen receptors in other estrogen responsive tissues. Scatchard and Hill plot analyses of the properties of receptor-ligand binding indicate the presence of a single site, and the absence of cooperative binding. Unlabeled E2 but not testosterone, dexamethasone or progesterone compete with [3H] 17 beta-estradiol for binding sites. The affinity, specificity and non-cooperative nature of the estrogen binding sites are identical to those observed in other estrogen-responsive tissues. These cells may provide a novel model in which to study the effects of estrogens on the proliferation, differentiation and function of vascular smooth muscle cells.

Animals↗
PubMed1996

MDA435/LCC6 and MDA435/LCC6MDR1: ascites models of human breast cancer.

We have established a novel ascites tumour model (MDA435/LCC6) from the oestrogen receptor-negative, invasive and metastatic MDA-MB-435 human breast cancer cell line. MDA435/LCC6 cells grow as both malignant ascites and solid tumours in vivo in nude mice and nude rats, with a tumour incidence of approximately 100%. Untreated mice develop ascites following i.p. inoculation of 1 x 10(6) cells and have a reproducible life span of approximately 30 days, with all animals dying within a 48 h period. The in vivo response of MDA435/LCC6 ascites to several cytotoxic drugs, including doxorubicin, etoposide (VP-16), BCNU and mitomycin C, closely reflects the activity of these single agents in previously untreated breast cancer patients. MDA435/LCC6 cells also retain the anchorage-dependent and anchorage-independent in vitro growth properties of the parental MDA-MB-435 cells, and can be used in standard in vitro drug screening assays. The drug resistance pattern of the MDA435/LCC6 cells suggests that they may have few active endogenous drug resistance mechanisms. To generate a model for the screening of MDR1-reversing agents, MDA435/LCC6 were transduced with a retroviral vector directing the constitutive expression of the MDR1 cDNA, producing a cell line with a classical MDR1 resistance pattern (MDA435/LCC6MDR1). THese ascites models may be a viable alternative to the murine leukaemia ascites (L1210, P388) and, in conjunction with other breast cancer cell lines, facilitate the in vitro and in vivo screening of new cytotoxic drugs and drug combinations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14,000 cases and 32,000 controls in the United Kingdom. The International Studies of Infarct Survival (ISIS) Collaborators.

OBJECTIVES: To assess the effects of cigarette smoking on the incidence of non-fatal myocardial infarction, and to compare tar in different types of manufactured cigarettes. METHODS: In the early 1990s responses to a postal questionnaire were obtained from 13,926 survivors of myocardial infarction (cases) recently discharged from hospitals in the United Kingdom and 32,389 of their relatives (controls). Blood had been obtained from cases soon after admission for the index myocardial infarction and was also sought from the controls. 4923 cases and 6880 controls were current smokers of manufactured cigarettes with known tar yields. Almost all tar yields were 7-9 or 12-15 mg/cigarette (mean 7.5 mg for low tar (< 10 mg) and 13.3 for medium tar (> or = 10 mg). The cited risk ratios were standardised for age and sex and compared myocardial infarction rates in current cigarette smokers with those in non-smokers who had not smoked cigarettes regularly in the past 10 years. RESULTS: At ages 30-49 the rates of myocardial infarction in smokers were about five times those in non-smokers (as defined); at ages 50-59 they were three times those in non-smokers, and even at ages 60-79 they were twice as great as in non-smokers (risk ratio 6.3, 4.7, 3.1, 2.5, and 1.9 at 30-39, 40-49, 50-59, 60-69, 70-79 respectively; each 2P < 0.00001). After standardisation for age, sex, and amount smoked, the rate of non-fatal myocardial infarction was 10.4% (SD 5.4) higher in medium tar than in low tar cigarette smokers (2P = 0.06). This percentage was not significantly greater at ages 30-59 (16.6% (7.1)) than at 60-79 (1.0% (8.5)). In both age ranges the difference in risk between cigarette smokers and non-smokers was much larger than the difference between one type of cigarette and another (risk ratio 3.39 and 3.95 at ages 30-59 for smokers of similar numbers of low and of medium tar cigarettes, and risk ratio 2.35 and 2.37 at ages 60-79). Most possible confounding factors that could be tested for were similar in low and medium tar users, with no significant differences in blood lipid or albumin concentrations. CONCLUSION: The present study indicates that the imminent change of tar yields in the European Union to comply with an upper limit of 12 mg/cigarette will not increase (and may somewhat decrease) the incidence of myocardial infarction, unless they indirectly help perpetuate tobacco use. Even low tar cigarettes still greatly increase rates of myocardial infarction, however, especially among people in their 30s, 40s, and 50s, and far more risk is avoided by not smoking than by changing from one type of cigarette to another.

Adult↗