What should be done about interval breast cancers?
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Breast Neoplasms↗
Biomedical subjects
M G Wallis
Publications and source records attributed to M G Wallis.
Classifying interval cancers.
No definitive way of classifying interval breast cancers (cancers presenting between screening rounds) has been determined, yet their number and classification forms one of the quality assurance (QA) standards for the National Health Service Breast Screening Programme (NHSBSP). This study was undertaken to identify how different screening centres undertake this process, and to compare the classifications obtained when a test set of mammograms was reviewed using three different methods. A questionnaire was sent to the 17 Regional UK breast screening QA centres. Twelve (80%) of the 15 centres completing the questionnaire had a formal method for reviewing interval cancers. Five of these (33%) attempted to simulate screening by mixing the interval cancers with other screening films. In 11 (73%) centres, a group (size range 3-14) of radiologists was involved. In a simulated film viewing exercise we assessed whether different methods of classification would alter the number of interval cancers classified as false negative (where an abnormality suspicious of malignancy can be identified on review of the original screening films). Six radiologists reviewed a set of 50 interval cancers by three different methods: independent reading of the interval cancers mixed with screening mammograms; independent reading of the interval cancers on their own; and finally a consensus opinion of the interval cancers alone using the films taken at diagnosis. No discussion or review of these cases had taken place prior to the study. The number of interval cancers classified as false negative increased by 10% when they were reviewed in isolation compared to review among 'normal' screening films. The false negative rate varied widely (4% to 56% P < 0.01) depending on the criteria required to fulfil a false negative interval cancer classification--whether only one, a majority, or all of the radiologists were required to see the abnormality on the original screening films. In order for inter-unit and regional comparisons to be useful, a standard review method of mixing the interval cancer films with normal screening films and using a consensus opinion by a minimum of three external reviewers is suggested.
Breast Neoplasms↗
The NAM1 protein (NAM1p), which is selectively required for cox1, cytb and atp6 transcript processing/stabilisation, is located in the yeast mitochondrial matrix.
The NAM1 nuclear gene was shown to control the stability and/or processing of mitochondrial transcripts of the cytochrome b, cytochrome oxidase subunit I and ATP synthase subunit VI genes [Groudinsky O., Bousquet I., Wallis M. G., Slonimski, P. P. & Dujardin G. (1993) Mol. Gen. Genet. 240, 419-427]. In order to better understand the mode of action of the NAM1 gene product, we have examined its intracellular fate. A fusion plasmid enabling bacterial over-expression of the corresponding protein-A-NAM1 cognate was constructed and subsequently employed as an antigen to raise polyclonal antibodies. These antibodies specifically recognise a 50-kDa protein which purifies along with the mitochondria and corresponds to NAM1p. Submitochondrial localisation experiments show that NAM1p is a soluble protein, located interior to the mitoplasts. Matricial location is a strong argument in favour of a direct interaction of NAM1p with particular mitochondrial transcripts and leads us to propose a model in which NAM1p could be an RNA-convoying protein stabilising and directing mitochondrial transcripts towards the inner face of the inner membrane where translation and assembly seem to occur.
Base Sequence↗
Mammographic film density and detection of small breast cancers.
From its inception, the UK National Breast Screening Programme (NHSBSP) has recognized that optimum image quality of the mammographic screening test is a key objective. The overall optical density of the mammography film is one of the factors expected to have a significant effect on the image quality of the mammogram with the potential to influence cancer detection. In a previous review of the performance of mammography equipment in the NHSBSP, it was observed that there was a very wide range in the mammographic film densities used at different breast screening centres. In this study a mammography test object was used to show experimentally that, for a typical mammography system, image quality increased substantially with increased film density. Summary data was therefore requested from radiologists in the NHSBSP on the rate of detection of small invasive cancers (diam. < or = 10 mm) and the typical film density used during that year. Proforma were completed for 61 annual sets of results from 31 screening centres involving over 500,000 women. Where centres reported using film densities of less than 1.2D the average small cancer detection rate was 0.12% +/- 0.01%, as compared to an average of 0.17% +/- 0.01% for centres using higher film densities. The results indicate that there is a need for national guidelines in the setting of film densities, and a range for target film densities of 1.4D to 1.8D has been suggested. Attention to optimizing image quality by increasing film density is of particular importance to any screening centre where film densities of less than 1.2D are used, as there may be the potential to increase the detection of small breast cancers by as much as 50%.
Breast Neoplasms↗
The NAM1/MTF2 nuclear gene product is selectively required for the stability and/or processing of mitochondrial transcripts of the atp6 and of the mosaic, cox1 and cytb genes in Saccharomyces cerevisiae.
The NAM1/MTF2 gene was firstly isolated as a multicopy suppressor of mitochondrial splicing deficiencies and independently as a gene of which a thermosensitive allele affects mitochondrial transcription in organello. To determine which step in mitochondrial RNA metabolism is controlled in vivo by the NAM1 gene, mitochondrial transcripts of seven transcription units from strains carrying an inactive nam1::URA3 gene disruption in various mitochondrial genetic backgrounds were analysed by Northern blot hybridisations. In a strain carrying an intron-containing mitochondrial genome, the inactivation of the NAM1 gene led to a strong decrease in (or total absence of) the mosaic cytb and cox1 mRNAs and in transcripts of the atp6-rf3/ens2 genes, which are co-transcribed with cox1. Neither the accumulation of unspliced cytb or cox1 pre-mRNAs, nor that of excised circular intron molecules of ai1 or ai2 were observed, but the abundance of the bi1 and ai7 lariats was comparable to that observed in the wild-type strain, thus demonstrating that transcription of the cytb and cox1 genes does occur. In strains carrying the intron-less mitochondrial genome with or without the rf3/ens2 sequence, wild-type amounts of cytb and cox1 mRNAs were detected while the amount of the atp6 mRNA was always strongly decreased. The abundance of transcripts from five other genes was either slightly (21S rRNA) or not at all (cox2, cox3, atp9 and 15S rRNA) affected by the nam1 inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Complex sclerosing lesions (radial scars) of the breast can be palpable.
Complex sclerosing lesion (CSL)/radial scar and carcinoma of breast can both present mammographically as stellate lesions. The mammographic features used to distinguish these two entities are reported as being unreliable. All reports to date indicate that CSLs are not palpable. Of the 54,407 women screened in the first 2 1/2 years of the Warwickshire, Solihull and Coventry Breast Screening Service, 24 histologically-proven CSLs were identified. This represents an incidence of 0.04%. In six (25%) of these patients a corresponding clinically-palpable abnormality was identified. We found no imaging or histological features that differentiated the palpable lesions from the impalpable lesions. It is important not to assume that a palpable stellate lesion is a carcinoma.
Breast↗
A review of false negative mammography in a symptomatic population.
A review of the mammograms of 871 patients with breast cancer from a symptomatic clinic performed at the General Hospital, Birmingham between 1980 and 1988 revealed an overall false negative rate of 8.6%. There has been a steady fall in the number of cancers missed per year from the commencement of review, and this reduction has been more consistent with improvements in radiographic equipment and technique, particularly the introduction of a radiographic grid. In half of the cases the tumour was missed because no radiological abnormality was detectable, even on reviewing the films, and this rate has remained remarkably stable over the study period, emphasizing the importance of a clinical examination in symptomatic women. Comparison of the histological diagnoses revealed similar percentages of ductal carcinomas, 89.6% in the true positive group compared with 85% in the false negative group. Of the false negative carcinomas, 5.5% were medullary tumours compared to 0.8% in the true positive group.
Adult↗
Isolation and partial characterization of an extradiol non-haem iron dioxygenase which preferentially cleaves 3-methylcatechol.
A purification procedure has been developed for an extradiol dioxygenase expressed in Escherichia coli, which was originally derived from a Pseudomonas putida strain able to grow on toluidine. Physical and kinetic properties of the enzyme have been investigated. The enzyme has a subunit Mr of 33,500 +/- 2000 by SDS/polyacrylamide-gel electrophoresis. Gel filtration indicates a molecular mass under non-denaturing conditions of 120,000 +/- 20,000. The N-terminal sequence (35 residues) of the enzyme has been determined and exhibits 50% identity with other extradiol dioxygenases. Fe(II) is a cofactor of the enzyme, as it is for other extradiol dioxygenases. The reactivity of this enzyme towards catechol and methyl-substituted catechols is somewhat different from that seen for other catechol 2,3-dioxygenases, with 3-methylcatechol cleaved at a higher rate than catechol or 4-methylcatechol. Km values for these substrates with this enzyme are all around 0.3 microM. The enzyme exhibits a bell-shaped pH profile with pKa values of 6.9 +/- 0.1 and 8.7 +/- 0.1. These results are compared with those found for other extradiol dioxygenases.
Amino Acid Sequence↗
Are three views necessary to examine acute ankle injuries?
In a retrospective review of the radiographs of 945 patients whose ankles were X-rayed for acute trauma over a 6 month period 95.3% of the 128 fractures identified were seen on anteroposterior and lateral films. The identification of six additional minor fractures by means of the 15 degrees internal oblique radiograph did not alter the management of individual patients and it is concluded that the routine use of oblique views is not justified. Radiological evidence of soft tissue swelling was present in 125 of the 128 fractures. The three patients in whom it was not seen had clinical evidence of local swelling and bruising. These findings indicate that fractures are highly unlikely to be present in the absence of local soft tissue swelling.
Adolescent↗
The prevalence of pleural effusions in pre-eclampsia: an ultrasound study.
A prospective ultrasound study was undertaken to investigate the prevalence of pleural effusion in patients with moderate or severe pre-eclampsia. The costophrenic angles of 34 consecutive patients were scanned postpartum with a real-time sector scanner. Six patients had pleural effusions. These patients did not have a greater degree of hypertension or proteinuria than the group without pleural effusion but had early severe disease requiring early delivery. The prematurity of these infants resulted in tenfold increase in perinatal death.
Adult↗