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C Warren

Publications and source records attributed to C Warren.

At least 19 recordsLinked to original sources

Comparative evaluation of the VITEK 2 Advanced Expert System (AES) in five UK hospitals.

OBJECTIVES: We carried out an evaluation of VITEK 2 in five UK laboratories, comparing results with 'gold standard' agar-dilution MIC data, assessing its ability to recognize resistant phenotypes and comparing results with those generated by routine antimicrobial susceptibility testing methods. METHODS: Laboratories tested a collection of 82 strains selected on the basis of their challenging and characterized resistance mechanisms. RESULTS: In comparison with the reference MIC method, VITEK 2 gave an essential agreement of 304/315 (enterococci), 1619/1674 (staphylococci) and 2937/3074 (Gram-negative bacilli): overall 96.0% agreement. Corresponding category (SIR) agreements with VITEK 2 were 247/252, 1496/1561 and 2478/2626 (overall 95.1%). Using five routine methodologies, category agreements ranged from 58/63 to 45/45; 222/232 to 174/174, and 333/372 to 250/259 for the three organism groups with an overall agreement of 95.0%. In contrast to VITEK 2 Advanced Expert System (AES), routine microbiology laboratories did not attempt to detect resistance mechanisms for every antibiotic studied. VITEK 2 AES detected all 19 resistance mechanisms in enterococci: where applicable, routine methods detected 14, 10 and 10. Of 30 resistance mechanisms in staphylococci, VITEK 2 AES detected 25 compared with 23, 20, 17 and 18 detected by routine methods. Finally, of 44 resistance mechanisms in Gram-negative bacilli, VITEK 2 AES detected 30 compared with 30, 23, 15 and 10 detected by routine methods. CONCLUSIONS: VITEK 2 performed susceptibility tests accurately and the AES detected and interpreted resistance mechanisms appropriately. Heavy inocula in a liquid medium possibly favour better expression of certain resistance determinants. Although certain routine microbiology methods performed adequately, VITEK 2 AES offers a rapid, standardized method suited to laboratories lacking experience of resistance mechanisms and/or those not testing an appropriate number, or range, of antibiotics to detect resistance phenotypes.

Bacteria↗

Identification of recurrent regions of chromosome loss and gain in vestibular schwannomas using comparative genomic hybridisation.

BACKGROUND: Schwannomas are benign tumours of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). The NF2 gene is a tumour suppressor on chromosome 22. Loss of expression of the NF2 protein product, merlin, is universal in both sporadic and NF2 related schwannomas. The GTPase signalling molecules RhoA and Rac1 regulate merlin function, but to date only mutation in the NF2 gene has been identified as a causal event in schwannoma formation. METHODS: Comparative genomic hybridisation (CGH) was used to screen 76 vestibular schwannomas from 76 patients (66 sporadic and 10 NF2 related) to identify other chromosome regions that may harbour genes involved in the tumorigenesis. RESULTS: The most common change was loss on chromosome 22, which was more frequent in sporadic than in NF2 related tumours. Importantly, eight tumours (10%) showed gain of copy number on chromosome 9q34. Each of the two NF2 patients who had received stereotactic radiotherapy had non-chromosome 22 changes, whereas only one of eight non-irradiated NF2 patients had any chromosome changes. Three tumours had gain on 17q, which has also been reported in malignant peripheral nerve sheath tumours that are associated with neurofibromatosis type 1. Other sites that were identified in three or fewer tumours were regions on chromosomes 10, 11, 13, 16, 19, 20, X, and Y. CONCLUSIONS: These findings should be verified using techniques that can detect smaller genetic changes, such as microarray-CGH.

Adolescent↗

Chromosomal radiosensitivity in young cancer patients: possible evidence of genetic predisposition.

PURPOSE: To investigate the G2 chromosomal radiosensitivity of patients with cancers diagnosed when the patients are less than 20 years of age. Earlier studies demonstrated an enhanced sensitivity in substantial proportions of patients with breast or colorectal cancer, and in early onset head and neck cancer cases. Heritability of chromosomal radiosensitivity in families of breast cancer patients was also demonstrated. It is suggested that elevated sensitivity in this assay could be a marker of genetic predisposition to cancer, mediated through inherited genetic determinants of low penetrance. MATERIALS AND METHODS: Stimulated lymphocytes were exposed to 0.5 Gy X-rays in the G2-phase of the cell cycle and chromatid aberrations were scored in metaphase cells. RESULTS: The assay was performed on 32 patients with early onset cancers (aged 0.5-19 years) of various types and their sensitivity was compared with that of 41 young normal controls (0.25-19 years) and 32 adult normals (20-60 years). The proportion of cases showing enhanced sensitivity in the three groups was 44, 15 and 10%, respectively. The difference between the young patients and normals was highly significant (p = 0.004). CONCLUSIONS: The results suggest the possibility that a substantial proportion of early onset cancers are associated with the inheritance of predisposing genes of low penetrance. However, support for this hypothesis requires that the heritability of chromosomal radiosensitivity be demonstrated in family members. In addition, a larger study is now required to investigate the chromosomal radiosensitivity of specific early onset cancers.

Adolescent↗

Tropical warts.

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Adult↗

Chromosomal radiosensitivity as a marker of predisposition to common cancers?

We previously found that 40% of breast cancer patients showed enhanced sensitivity to X-ray induced chromosome damage in G(2)lymphocytes and suggested that this might indicate a low penetrance predisposition to breast cancer, for which there is good epidemiological evidence. We have now tested the hypothesis that elevated G(2)radiosensitivity is a marker of such predisposition to other common cancers. We tested patients with colorectal cancer, for which there is also good epidemiological evidence of inherited risk in a substantial proportion of cases, and patients with cancers having a strong environmental aetiology (lung and cervix). We also repeated our study of breast cancer cases and tested patients with chronic diseases other than cancer. The results support our hypothesis, in that 30% (12/37) of colorectal cases showed enhanced sensitivity compared with 9% (6/66) of normal healthy controls (P = 0.01), whereas the proportions of sensitive cervix (11%, 3/27, P = 0.72) and lung cancer cases (23%, 8/35, P = 0.07) were not significantly above normals. We confirmed the enhanced sensitivity of 40% (12/31, P = 0.001) of breast cancer patients and found that patients with non-malignant disease had a normal response in the assay (12%, 4/34, P = 0.73). We suggest that enhanced G(2)chromosomal radiosensitivity is a consequence of inherited defects in the ability of cells to process DNA damage from endogenous or exogenous sources, of a type that is mimicked by ionizing radiation, and that such defects predispose to breast and colorectal cancer.

Adult↗

Science, policy, stakeholders, and fish consumption advisories: developing a fish fact sheet for the Savannah River.

In recent years there has been a startling rise in the issuance of fish consumption advisories. Unfortunately, compliance by the public is often low. Low compliance can be due to a number of factors, including confusion over the meaning of advisories, conflicting advisories issued by different agencies, controversies involving health benefits versus the risks from consuming fish, and an unwillingness to act on the advisories because of personal beliefs. In some places, such as along the Savannah River, one state (South Carolina) had issued a consumption advisory while the other (Georgia) had not, although at present, both states now issue consumption advisories for the Savannah River. Herein we report on the development of a fish fact sheet to address the confusing and conflicting information available to the public about consuming fish from the Savannah River. The process involved interviewing fishers to ascertain fishing and consumption patterns, evaluating contaminant levels and exposure pathways, discussing common grounds for the provision of information, and consensus-building among different regulatory agencies (US Environmental Protection Agency, South Carolina Department of Health and Environmental Control, Georgia Department of Natural Resources) and the Department of Energy. Consensus, a key ingredient in solving many different types of "commons" problems, was aided by an outside organization, the Consortium for Risk Evaluation with Stakeholder Participation (CRESP). The initial role for CRESP was to offer scientific data as a basis for groups with different assumptions about risks to reach agreement on a regulatory response action. The process was an example of how credible science can be used to implement management and policies and provide a basis for consensus-building on difficult risk communication issues. The paper provides several lessons for improving the risk process from stakeholder conflicts, through risk assessment, to risk management. It also suggests that consensus-building and risk communication are continuing processes that involve assimilation of new information on contaminants and food-chain processes, state and federal law, public policy, and public response.

Animals↗

Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States.

SETTING: Health care workers and medical students in the United States subject to annual tuberculin skin testing. OBJECTIVE: To use skin testing with Mycobacterium avium sensitin (MAS) to determine contemporary rates of infection with non-tuberculous mycobacteria (NTM) and their effect on reactions to M. tuberculosis purified protein derivative (PPD). DESIGN: Dual skin testing was performed with PPD and MAS on 784 health care workers and medical students in the northern and southern US. MAS reactions that were > or = 5 mm and also > or = 3 mm larger than the PPD reaction were defined as MAS dominant and due to NTM. RESULTS: MAS reactions were > or = 5 mm in 40% and > or = 15 mm in 18% of subjects; 95% were MAS dominant. MAS dominant reactions were more common in the south than the north (P < 0.001). PPD reactions were > or = 15 mm in 3% of subjects. PPD reactions > or = 15 mm were more common among males, foreign born subjects and subjects with BCG immunization (all P < 0.001). MAS dominant reactions were found in 82% of subjects with 5-9 mm PPD reactions and 50% with 10-14 mm PPD reactions; these reactions were more common among whites (P = 0.046), US-born (P = 0.038) and subjects without BCG immunization (P = 0.004). CONCLUSIONS: Infections with NTM are responsible for the majority of 5-14 mm PPD reactions among US-born health care workers and medical students subject to annual tuberculin testing.

Adult↗

Establishing community partnerships: providing better oral health care to underserved children.

A community partnership between a dental hygiene school and a social service program was designed to improve oral health outcomes and reduce disparities among children. This resulted in a preventive oral hygiene care project that complimented the dental hygiene program's didactic curriculum. The children received much needed oral health care and education, while the experiences enhanced dental hygiene student learning by applying the principles for planning, implementing, and evaluating dental health programs; establishing a context for understanding the prevalence of oral disease as well the disparity among population subsets; and developing a variety of clinical skills. Oral health professionals and dental hygiene programs may find this partnership a prototype of a highly productive and beneficial community health experience that could be incorporated, in part or in it's entirety, into their own community health projects.

Adolescent↗

Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: There is a need for rapid and reliable tests for the prediction of normal tissue responses to radiotherapy, as this could lead to individualization of patient radiotherapy schedules and thus improvements in the therapeutic ratio. Because the use of cultured fibroblasts is too slow to be practicable in a clinical setting, we evaluated the predictive role of assays of lymphocyte chromosomal radiosensitivity in patients having radiotherapy for breast cancer. MATERIALS AND METHODS: Radiosensitivity was assessed using a micronucleus (MN) assay at high dose rate (HDR) and low dose rate (LDR) on lymphocytes irradiated in the G(0) phase of the cell cycle (Scott D, Barber JB, Levine EL, Burril W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a frequency of radiosensitive cases among breast cancer patients: a test for predispostion? Br. J. Cancer 1998;77;614-620) and an assay of G(2) phase chromatid radiosensitivity ('G(2) assay') (Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet 1994; 344: 1444). In a study of acute reactions, blood samples were taken from breast cancer patients before the start of radiotherapy, and the skin reaction documented. 116 patients were tested with the HDR MN assay, 73 with the LDR MN assay and 123 with the G(2) assay. In a study of late reactions, samples were taken from a series of breast cancer patients 8-14 years after radiotherapy and the patients assessed for the severity of late effects according to the'LENT SOMA' scales. 47 were tested with the HDR assay, 26 with the LDR assay and 19 with the G(2) assay. For each clinical endpoint, patients were classified as being normal reactors or 'highly radiosensitive patients' (HR patients (Burnet NG. Johansen J, Turesson I, Nyman J. Describing patients' normal tissue reactions: Concerning the possiblity of individualising radiotherapy dose presciptions based on potential predictive assays of normal tissue radiosensitivity. Int. J. Cancer 1998;79:606-613)). RESULTS: The HR patients could be identified in some of the assays. For example, for acute skin reactions, 9/123 patients were judged as HR; they had significantly higher G(2) scores than normal reactors (P=0.004). For the late reactions, the mean HDR MN scores were higher for the 4/47 patients who had severe telangiectasia (P=0.042) and the 8/47 patients had severe fibrosis (P=0.055). However, there were no trends towards increased chromosomal radiosensitivity with the micronucleus scores at HDR or LDR, or with G(2) chromosomal radiosensitivity. CONCLUSIONS: While these results support the concept of using lymphocytes to detect elevated sensitivity to radiotherapy (as an alternative to fibroblasts), these assays are unlikely to be of assistance for the prediction of normal tissue effects in the clinic in their present form.

Adult↗

Effects of portal injection of 2,5-anhydro-D-mannitol on pancreatic hormone responses to exercise in rats.

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) has been shown to act specifically in liver by decreasing liver ATP and by blocking glycogenolysis and gluconeogenesis. The present investigation was designed to determine the effects of the administration of 2,5-AM on pancreatic hormone responses during a situation of increased energy demand such as physical exercise, and by comparison to the resting response, to test the possibility that the hormonal effects of 2,5-AM during exercise may be dissociated from a decrease in blood glucose levels. Adrenodemedullated rats were injected intraportally with a dose of 200 mg/kg of 2,5-AM (50 mg/ml) or by an equivalent volume of saline (0.9% NaCl) before being submitted to a 30-min treadmill run (26 m/min, 0% grade). Administration of 2,5-AM at rest resulted in a significant (P < 0.05) decrease of plasma glucose and insulin levels and an increase in beta-hydroxybutyrate concentrations. During exercise, administration of 2,5-AM, as compared to resting values, resulted in a larger decrease in glucose, a similar decrease in insulin, and a much larger increase in glucagon, glucagon/insulin molar ratio, and beta-hydroxybutyrate concentrations. It is concluded that exercise amplifies some of the metabolic and hormonal effects of 2,5-AM, and that these effects cannot all be explained by the decrease in blood glucose levels.

3-Hydroxybutyric Acid↗

Hospice access and use by African Americans: addressing cultural and institutional barriers through participatory action research.

This article describes a participatory action research project addressing the problem of African American access to and use of hospice. Qualitative interviews conducted with six African American pastors resulted in the identification of major themes used for development of a scale to measure barriers to hospice. A subsequent quantitative study documenting these barriers was conducted with 127 African American and European Americans. Results of both studies, which were used to further social action efforts in the community, indicated the cultural barriers of differences in values regarding medical care and differences in spiritual beliefs between African Americans and European Americans. Results also indicated institutional barriers, including lack of knowledge of services, economic factors, lack of trust by African Americans in the health care system, and lack of diversity among health care staff. Implications for social work practice and policy are discussed.

Black or African American↗

Geographical variations in AIDS knowledge and attitude among adolescent girls of Jamaica.

This article examines geographical differences in AIDS knowledge and attitudes. Data from a survey of 900 adolescent girls in the Caribbean nation of Jamaica indicate significant differences across geography in AIDS knowledge and attitude. Adolescent girls in more central areas have access to different and more sources of information than those in more remote areas. They are also more likely to know persons with AIDS, be more knowledgeable about the clinical manifestations of AIDS, and be more realistic in assessing their susceptibility of HIV. The implications of geographical differences for AIDS education efforts are discussed.

Acquired Immunodeficiency Syndrome↗

Metabolic and hormonal responses to exercise in partially hepatectomised rats.

To characterise how the liver affects metabolic and hormonal exercise responses, hepatectomised (70%; HX) rats were submitted to a 30- or 50-min treadmill exercise (26 m/min, 0% slope) 48 hr or 7 days after surgery (reduced or normal liver mass, respectively). To determine whether metabolic effects of liver mass reduction during exercise were caused by reduced capacity of the liver to produce glucose, metabolic and hormonal responses to the same exercise protocol were measured in 48-hr HX rats. Euglycemia, maintained by exogenous glucose infusion, produced attenuated lactate, insulin, and glucagon values in 48-hr HX rats but did not affect FFA, glycerol, and plasma catecholamine responses. Results indicate that metabolic and hormonal exercise responses are amplified in 48-hr HX rats. Maintaining euglycemia in 48-hr HX rats during exercise does not reduce all responses. Intrahepatic events, similar to those in a short-term (48-hr) HX liver, may influence metabolic and hormonal exercise responses.

Animals↗

Effects of hepatic portal infusion of deionized water on metabolic and hormonal responses to exercise in rats.

The present study was conducted to investigate the in vivo effects of an intrahepatic infusion of deionized water during exercise in rats. Adrenodemedullated male Sprague-Dawley rats were continuously infused for 30 min either at rest or during treadmill exercise (26 m/min, 0% grade). Rats were randomly assigned to one of three infusion conditions (52 micro ul/min) with either deionized water (PW) or saline (PS; NaCl; 0.9%) via the hepatic portal vein or deionized water through the jugular vein (JW). The exercise period caused a significant (P < 0.05) decrease in liver glycogen and relative liver water content and peripheral and portal blood glucose and insulin while increasing peripheral and portal glucagon and K+ plasma concentrations. These responses, with the exception of K+, were not influenced by the different types of infusions. The increase in K+ during exercise was significantly (P < 0.05) higher in JW rats than in the PW and PS groups. Both the infusion and exercise protocols did not significantly alter the liver weight-to-body weight ratio, plasma osmolality, free fatty acids, beta-hydroxybutyrate, Na+, Cl-, vasopressin, and catecholamine concentrations. It is concluded that an hepatic portal infusion of deionized water does not specifically alter the metabolic and hormonal responses to exercise in rats.

Animals↗