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Biomedical subjects

M Cummings

Publications and source records attributed to M Cummings.

At least 19 recordsLinked to original sources

The effects of higher cigarette prices on tar and nicotine consumption in a cohort of adult smokers.

The objective of this paper is to estimate the demand for tar and nicotine in cigarettes as a function of cigarette prices in a cohort of cigarette 11,966 smokers followed for 5 years. Data for the analysis come from a longitudinal telephone survey of 11,966 smokers who were interviewed in 1988 and 1993 as part of the Community Intervention Trial for Smoking Cessation (COMMIT). Separate models are estimated for three age groups to account for differences in levels of addiction and brand loyalty across age. We found that smokers respond to higher cigarette prices by reducing the number of cigarettes smoked per day but also by switching to cigarettes that are higher in tar and nicotine per cigarette.

Adult↗

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study.

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC ) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC.

Adult↗

Reduced expression of intercellular adhesion molecule-1 in ovarian adenocarcinomas.

Ovarian adenocarcinomas develop as the result of multiple genetic and epigenetic changes in the precursor ovarian surface epithelial (OSE) cells which result in a malignant phenotype. We investigated changes in gene expression in ovarian adenocarcinoma using a cDNA array containing 588 known human genes. We found that intercellular adhesion molecule-1 (ICAM-1) was expressed at lower levels in the ovarian tumour cell lines OAW42, PEO1 and JAM than in the immortalised human ovarian surface epithelial cell line HOSE 17.1. Further investigation revealed ICAM-1 was expressed in the surface epithelium of normal ovaries and both mRNA and protein expression levels were reduced in the majority of ovarian adenocarcinoma cell lines and primary tumours. ICAM-1 expression was increased in 8/8 cell lines treated with the de novo methyltransferase inhibitor 5-aza-2'-deoxycytidine, indicating that methylation of CpG islands may play a role in the down-regulation of its expression in primary tumours. There was a significant association between patients whose tumours expressed ICAM-1 and survival (P = 0.03), suggesting that expression levels of ICAM-1 may have clinical relevance.

Adenocarcinoma↗

Low frequency of genetic lesions in Wilms tumors by representational difference analysis.

Genomic representational difference analysis (RDA) was carried out on a total of nine Wilms tumors and one cystic partially differentiated nephroblastoma (CPDN; a sub-type of Wilms) to look for novel genetic deletions involving tumor suppressor genes. Genomic DNA from either short-term cultured Wilms tumor cells or a WT xenograft was used to create driver representations, and genomic DNA from matched normal kidney or normal kidney cells grown in short-term culture was used to create the tester. Genuine difference products were obtained from only one of the tumors. However, none of these fragments were found to be deleted in the original tumor biopsy, microdissected tumor or in the lung metastasis from this patient. It is, therefore, likely that the deletions were due to random losses associated with the genetic instability of the cultured cells from this particular tumor. We did not isolate difference products from any of the other tumors, showing that they did not have chromosomal losses, homozygous deletions or regions of LOH that were detectable by RDA.

Animals↗

Standards for reporting interventions in controlled trials of acupuncture: the STRICTA recommendations.

Acupuncture treatment and control group interventions in parallel-group randomised trials of acupuncture are not always precisely reported. In an attempt to improve standards, an international group of experienced acupuncturists and researchers devised a set of recommendations, designating them STRICTA: STandards for Reporting Interventions in Controlled Trials of Acupuncture. In a further consensus-building round, the editors of several journals helped redraft the recommendations. These follow the Consolidated Standards for Reporting Trials (CONSORT) format, acting as an extension of the CONSORT guidelines for the specific requirements of acupuncture studies. Participating journals are publishing the STRICTA recommendations and requesting prospective authors to adhere to them when preparing reports for publication. Other journals are invited to adopt these recommendations. The intended outcome is that interventions in controlled trials of acupuncture will be more adequately reported, thereby facilitating an improvement in critical appraisal, analysis and replication of trials.

Acupuncture Therapy↗

Percutaneous electrical nerve stimulation--electroacupuncture by another name? A comparative review.

Percutaneous electrical nerve stimulation (PENS) is a technique that has been described as a 'novel analgesic therapy'. A review was performed of the published literature in order to compare PENS with the author's knowledge and experience of the use of EA, specifically with regard to the stimulation parameters, the selection of points, and the reported efficacy. The conclusion of the review is that PENS is neither different in principle nor in practice from EA, and whilst the term accurately reflects the nature of the treatment, there is no substantial justification for referring to PENS as a novel therapy.

Electroacupuncture↗

Informed consent for acupuncture--an information leaflet developed by consensus.

Patients have the right to be fully informed about the likely benefits and risks of any proposed examination or treatment, and practitioners are obliged to obtain informed consent beforehand. Accurate information about the risks of acupuncture is available following publication of the results of two prospective surveys. At a joint meeting on the safety of acupuncture, members of the three largest UK professional bodies expressed a need to establish what information on risks patients should be given. A standard Information Leaflet was developed by consensus between thesc organisations, and is intended to be used as a stimulus for discussion of standard risks as well as any particular risks that might apply to individual patients. Additionally, it may be used as a form for written consent when this is required. To provide the context for using the Leaflet, the legal and ethical bases of informed consent for medical procedures are discussed.

Acupuncture↗

Expression of p53 in arsenic-related and sporadic basal cell carcinoma.

BACKGROUND: The TP53 gene has been shown to have an important role in the genesis of sporadic, presumably mainly sunlight-related, basal cell carcinoma (BCC). However, its role in arsenic-related BCCs is not clear, although the trivalent form of arsenic has been long recognized as a cause of BCC. Arsenic treatment has been shown to cause hypermethylation of the TP53 gene in lung carcinoma cell lines, but it is not known if this occurs in vivo in arsenic-related BCCs. OBJECTIVE: To compare the immunohistochemical expression of the p53 protein in arsenic-related and sporadic BCCs to determine if the expression pattern is consistent with gene silencing. SETTING: A research institute and hospital in Australia. CASES: One hundred seventeen white patients with 121 sporadic BCCs and 21 white patients with 92 arsenic-related BCCs. MAIN OUTCOME MEASURES: The expression and the intensity of p53 were scored semiquantitatively. Statistical analysis was performed using the chi2 test. RESULTS: Arsenic-related BCCs express p53 less often and at a lower intensity than sporadic BCCs (P = .001; 2-tailed test). The BCCs from sun-exposed sites, whether arsenic related or sporadic, more frequently showed overexpression of p53 than those from less-exposed areas (P = .004; 2-tailed test). The more aggressive subtypes of BCC show a higher level of expression of p53 than the less aggressive forms (P = .04; 2-tailed chi2 test). CONCLUSIONS: These results are consistent with the hypothesis that the TP53 gene is down-regulated by methylation in arsenic-related BCC, particularly those from less-exposed sites. However, an alternative possibility is that mutations in TP53 that stabilize the protein are less common in arsenic-related BCCs. Further analysis will be necessary to distinguish between these hypotheses.

Adult↗