Diagnostic accuracy of mammography readers and their memory performance have no correlation with each other.

INTRODUCTION: The study aims to determine if any association exists between visual memory performance and diagnostic accuracy performance in a group of radiologist mammogram readers. MATERIALS AND METHODS: One hundred proven mammograms (23 with cancers) were grouped into 5 sets of 20 cases, with sets being of equal difficulty. Pairs of sets were presented in 5 reads (40 cases per read, order random) to a panel of 8 radiologist readers (either present or past screening readers, with experience range from <1 year to >20 years). The readers were asked to either 'clear' or 'call back' cases depending on need for further workup, and at post-baseline reads to indicate whether each case was 'new' or 'old' (i.e. remembered from prior read). Two sets were presented only at baseline (40 cases per reader), and were used to calculate the reader's false recollection rate. Three sets were repeated post-baseline once or twice (100 cases per reader). Reading conditions were standardised. RESULTS: Memory performance differed markedly between readers. The number of correctly remembered cases (of 100 'old' cases) had a median of 10.5 and range of 0-58. The observed number of false recollections (of 40 'totally new' cases) had a median of 2 and range of 0-17. Diagnostic performance measures were mean (range): sensitivity 0.68 (0.54-0.81); specificity 0.82 (0.74-0.91); positive predictive value (PPV) 0.55 (0.50-0.65); negative predictive value (NPV) 0.89 (0.86-0.93) and accuracy 0.78 (0.76-0.83). Confidence intervals (CIs; 95%) for each reader overlapped for all the diagnostic parameters, indicating a lack of statistically significant difference between the readers at the 5% level. The most sensitive and the most specific reader showed a trend away from each other on sensitivity, specificity, NPV and PPV; their accuracies were 0.76 and 0.82, respectively, and their accuracy 95% CIs overlapped considerably. Correlation analysis by reader showed no association between observed memory performance and any of the diagnostic accuracy measures in our group of readers. In particular, there was no correlation between diagnostic accuracy and memory performance. CONCLUSION: There was no association between visual memory performance and diagnostic accuracy as a screening mammographer in our group of eight representative readers. Whether a radiologist has a good or a bad visual memory for cases, and in particular mammograms, should not impact on his or her performance as a radiologist and mammogram reader.

The application of computerized tomography (CT) to the dental ageing of children and adolescents.

INTRODUCTION: Following a mass disaster, the aim of the Disaster Victim Identification process is to establish the identity of the victims. The ageing screening process on victims in Victoria may now be complemented with the use of computerized tomography (CT), where previously any dental ageing analysis was performed using conventional radiographs. The aim of this study was to assess the accuracy of age estimation using the dental ageing method proposed by Moorrees, Fanning and Hunt (MFH) using CT images. Intra- and inter-rater variability between two raters, one experienced and one inexperienced, was also assessed. MATERIALS AND METHODS: The two raters were blinded to the ages of 96 deceased Australian children aged up to 15 years. Using three-dimensional (3D) shaded surface displays (SSD) and reformatted CT images, the age was first estimated based on prior experience alone, followed at a later date by the age estimation utilizing the MFH method. These estimates were then compared to the known chronological age. The results were statistically analyzed in a one-sample t-test, using the mean log-ratio of the estimated age to the chronological age. RESULTS: Our findings show that the experienced rater was more accurate in age estimation than the less experienced when using prior experience (p<0.0001). The use of reformatted CT images to perform an ageing estimate using the MFH method was found to systematically underestimate the chronological age by 10% by both raters (p=0.784). There was no significant difference between the two raters. Intra-rater reliability was high (p=0.135). CONCLUSIONS: CT can provide accurate estimates of dental ages. Prior experience with dental ageing and/or CT improves the accuracy. However, with the use of validated ageing charts, inexperienced raters can also achieve accurate age estimates using CT images.

Circle of Willis artery diameters on MR angiography: an Australian reference database.

The aim was to establish a reference range of measurements for all major Circle of Willis (COW) arteries for an Australian population of patients presenting for brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) that is typical of a tertiary referral hospital; and to report the prevalence and disease associations of COW variants in our patient population. All technically diagnostic MRI and MRA studies performed at our magnetic resonance (MR) centre in the calendar year 2006 were re-read by one reader who classified the COW anatomical layout and measured diameters of all the major vessels at defined locations. A subset of 30 was independently re-read by another reader and the interobserver measurement variability analyzed. Graphical analysis, with 95% confidence intervals (95CI), summary statistics reporting, t-testing for unpaired and for paired means, Hauck-Anderson (H-A) clinical equivalence testing and logistic regression analysis for categorical variables was performed as relevant. One hundred and seventy-one studies (of 187 eligible) formed the analysis population. All of our patients had vessels of comparable calibre regardless of MRI disease status, gender or COW variant (P > 0.05). Basilar artery (BA) diameter showed significant association with age, but other vessel diameters did not. The reference range is widely applicable, methodology straightforward and appears tolerant of interobserver variability. A number of discontinuous COW variants become more prevalent with age, perhaps from atherosclerotic occlusive disease. There was no association between COW variants, gender, aneurysm location or MRI disease status.

Drain-blocking techniques on blanket peat: A framework for best practice.

In recent years there has been a dramatic increase in artificial drain-blocking in world peatlands. The UK blanket peatlands have been severely drained over the past few decades but now drains are being blocked in an attempt to improve peatland environments. The drain-blocking has been a disparate process with limited knowledge transfer between organisations and within organisations operating in different geographic areas. Consequently, there has been no compilation of techniques used and their effectiveness. During this study thirty-two drain-blocked sites were surveyed and all the key stakeholders interviewed. Drain-blocking using peat turf was preferred by practitioners and was also the most cost-effective method. Peat turves were successful except on steep slopes, in areas of severe erosion, in very wet or very dry locations, or if the mineral substrate was exposed. A drain-blocking best practice guide is offered by this paper, providing information on the most suitable methods for blocking peatland drains under different circumstances. Additional considerations are provided for practitioners to ensure peatland drain-blocking is as successful as possible.

Stromal cell-derived receptor 2 and cytochrome b561 are functional ferric reductases.

Iron has a variety of functions in cellular organisms ranging from electron transport and DNA synthesis to adenosine triphosphate (ATP) and neurotransmitter synthesis. Failure to regulate the homeostasis of iron can lead to cognition and demyelination disorders when iron levels are deficient, and to neurodegenerative disorders when iron is in excess. In this study we show that three members of the b561 family of predicted ferric reductases, namely mouse cytochrome b561 and mouse and fly stromal cell-derived receptor 2 (SDR2), have ferric reductase activity. Given that a fourth member, duodenal cytochrome b (Dcytb), has previously been shown to be a ferric reductase, it is likely that all remaining members of this family also exhibit this activity. Furthermore, we show that the rat sdr2 message is predominantly expressed in the liver and kidney, with low expression in the duodenum. In hypotransferrinaemic (hpx) mice, sdr2 expression in the liver and kidney is reduced, suggesting that it may be regulated by iron. Moreover, we demonstrate the presence of mouse sdr2 in the choroid plexus and in the ependymal cells lining the four ventricles, through in situ hybridization analysis.

P53-dependent and -independent links between DNA-damage, apoptosis and mutation frequency in ES cells.

The hypothesis that p53 deficiency enhances the survival of DNA-damage bearing cells was investigated in wild-type and p53 mutant embryonic stem (ES) cells. Following UV-C irradiation, p53 is rapidly induced in wild-type cells and p53-dependent apoptosis follows within 8 h, resulting in the death of the majority of cells within 36 h. Increasing doses of UV-irradiation resulted in enhanced clonogenic survival of null cells as compared to wild-type. Amongst surviving clones, the Hprt mutation frequency was found to be dependent upon UV dose and influenced by p53 status. Treatment with ionizing radiation led to enhanced expression of p53 but resulted in little induction of apoptosis irrespective of p53 status. However, clonogenic potential was considerably reduced, particularly in wild-type cells which showed a tenfold lower survival than null cells. In contrast to the effects of UV-irradiation, the incidence of Hprt mutation did not differ significantly between wild-type and p53 null survivors. The data confirm that p53 restricts the numbers of cells bearing mutations that survive DNA damage induced by either agent, albeit by different mechanisms.

A partnership of care: an approach to the management of adults with cystic fibrosis.

Several factors occurring more or less simultaneously have led to a major change in the management of adults with cystic fibrosis at The Prince Charles Hospital, Brisbane. Less than 50 years ago, 80 per cent of infants born with cystic fibrosis did not survive the first two years of life. In Australia today, the median survival is around 30 years of age, with many surviving into their fourth decade (Landau & Ryan 1991, p 4). Recent developments in the management and treatment of cystic fibrosis provide an exciting and promising foundation for further development and a changing focus in cystic fibrosis management. Increased longevity has significant implications for the management of adults with cystic fibrosis. Until recently, most people with cystic fibrosis were managed within the paediatric setting, with the expectation that life expectancy would not exceed adolescence. In reality, there has been a dramatic increase in the number transferring from children's hospitals to adult facilities, and a subsequent need to provide optimal care to a group of patients coming to terms with their own perceptions of being adolescents with a life-shortening condition. From an organisational perspective, the increased demand for resources has generated the need to consider alternative methods of providing care. Such options include home intravenous therapy, day admission, alternative accommodation and education of staff in remote health centres. Home intravenous therapy has proven to be a popular alternative to hospital treatment and has significant implications for reducing lengths of stay and occupied bed-days. Within the current focus on best practice, developing strategies for providing optimal health care in the hospital setting are paramount. A multidisciplinary team focus based on a 'partnership of care' philosophy underpinned by best practice principles describes the approach adopted by the cystic fibrosis team at The Prince Charles Hospital that has led to successful outcomes in meeting challenges inherent in the care of young adults with cystic fibrosis.

Loss of heterozygosity at 5q21 in non-small cell lung cancer: a frequent event but without evidence of apc mutation.

Four genetic polymorphisms in the APC and MCC genes at chromosome 5q21 were analysed for loss of heterozygosity (LOH) in 97 primary squamous carcinomas and adenocarcinomas of the lung. LOH was identified in at least two polymorphic loci in 41 percent of informative cases. There was no significant difference in the frequency of LOH between squamous carcinomas and adenocarcinomas. Within the adenocarcinoma group, however, LOH appeared to be more common in tumours having a bronchial origin (5/9; 56 per cent) than in parenchymal adenocarcinoma (6/21; 29 per cent). All 32 tumours showing LOH at one or more polymorphic sites were examined for mutations in the mutation cluster region (MCR) of APC by single-strand conformational polymorphism (SSCP) analysis. Mutations were not detected in any of these cases. We therefore propose that it is likely that a tumour suppressor gene on 5q other than APC is involved in the pathogenesis of lung cancer.

Loss of Apc+ in intestinal adenomas from Min mice.

Allelic loss at the Apc locus in spontaneously occurring intestinal adenomas from mice heterozygous for the ApcMin nonsense mutation was analyzed using a site-specific quantitative polymerase chain reaction assay. All 97 of the intestinal adenomas analyzed showed extensive loss of the wild-type Apc (Apc+) allele. Quantitative polymerase chain reaction analysis of loci linked to Apc indicated loss of the chromosome carrying Apc+. Only one copy of the homologue carrying ApcMin remained in the intestinal adenomas. Possible reasons for the difference in the mechanism of Apc+ loss between human and Min mouse intestinal adenomas are discussed.

p53 dependence of early apoptotic and proliferative responses within the mouse intestinal epithelium following gamma-irradiation.

p53 is now well characterized as a tumour suppressor gene, with loss of normal p53 function being recorded as the commonest genetic event associated with human malignancy. In particular, its involvement with tumorigenesis within the intestine is well established. Normal p53 function has been shown to be crucial for the induction of apoptosis in tumour cell lines, murine thymocytes and murine haematopoietic cells following DNA damage. To elucidate further the role of p53 in the cellular response to DNA damage we have investigated the response to gamma-irradiation of crypt cells in vivo from the small and large intestine of mice bearing a constitutive p53 deletion. Four hours after gamma-irradiation, a time point at which wild type crypt cells show abundant apoptosis, crypt cells from p53-deficient mice differed in that they were completely resistant to the induction of apoptosis. The p53 dose dependence of this phenomenon was clearly shown by the intermediate level of apoptosis observed in p53 heterozygotes. Analysis of the mitotic index and the bromodeoxyuridine labelling index showed that two other responses of wild type crypts to gamma-irradiation, namely the G2 block and the reduction in bromodeoxyuridine incorporation, were both largely intact in p53 deficient animals. These observations demonstrate that p53 function is essential for a major component of the normal response to gamma-irradiation induced DNA damage in intestinal mucosal cells, and suggest that p53 deficiency permits a population of cells bearing DNA damage to escape the normal process of deletion.

Loss of heterozygosity of MCC is not associated with mutation of the retained allele in sporadic colorectal cancer.

The adenomatous polyposis coli (APC) gene, which transmits familial adenomatous polyposis, is frequently mutated in sporadic colorectal tumours. Acquired somatic mutations have also been reported in a second gene, mutated in colorectal cancer (MCC), which lies within 500 kb of APC on chromosome 5q21 and has thus been implicated in tumour development. Further evidence for an oncosuppressor gene other than APC on chromosome 5q comes from recent studies of lung, renal and hepatic cancers in which there is loss of heterozygosity of 5q21 but no somatic APC mutations. To investigate the relative importance of APC and MCC in sporadic colorectal cancer, we have assessed the extent of 5q21 allelic loss in 80 carcinomas. All informative tumours exhibiting allelic loss had deletions which included both APC and MCC. In 21 tumours with loss of heterozygosity in MCC we have screened the entire coding region of the gene for mutation of the retained allele and found no evidence for mutation. The data indicate that independent loss of MCC is a rare event, and that in cases where allele loss occurs mutation of the retained allele is uncommon. This suggests that MCC does not function as an independent tumour suppressor in the majority of colorectal cancers.

Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age.

An investigation as to whether any particular subgroup of patients with Hodgkin's disease was particularly likely to be Epstein-Barr virus (EBV) genome positive was made on samples from 95 patients. These were grouped according to age and Hodgkin's disease subtype, and analysed using Southern blot analysis. Most samples from children or adults aged 50 years or over contained detectable EBV genomes; samples from young adults were only rarely positive. The differences in EBV positivity by age were highly significant, but there was no significant association between EBV and histological subtype after allowing for the effect of age. The results support the hypothesis that Hodgkin's disease in different age groups may have different aetiologies, and suggest that EBV does have a pathogenetic role in Hodgkin's disease in children and older age groups.

Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples.

Thirty-five cases of Hodgkin's disease (HD) were analysed for the presence of Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) DNA. EBV genomes were detected in 11/35 cases while none of the cases was positive for HHV-6. Ten of the EBV-positive cases were subsequently analysed using a probe for the terminal region of the virus; the results suggested that the EBV-infected cells were clonally expanded. EBV subtypes specific DNA amplification was used to demonstrate that EBV subtype A, and not subtype B was present in the EBV-positive cases. The age distribution of the EBV-positive cases indicated a statistically significant trend for an increase in positivity with increasing age. This is the first indication that EBV is significantly associated with any subset of HD patients.

Karyotypic abnormalities and immunoglobulin gene rearrangements in Hodgkin's disease.

Biopsy samples from seven patients with Hodgkin's disease (HD) were examined for cytogenetic abnormalities and rearrangement of the genes encoding the immunoglobulin chains and T-cell receptor chains. Three samples demonstrated clonal rearrangements of both IgH and IgL genes. No rearrangements of the TCR beta genes were detected in any of the samples. Karyotypic abnormalities were also found but only in the three cases where a clonal rearrangement of the immunoglobulin genes was shown. Two of these three cases had multiple karyotypic abnormalities, with the remaining patient being trisomic for chromosome 16 as the sole abnormality. These results are discussed and compared with previous reports in the literature concerning HD.

Analysis of T-cell receptor and immunoglobulin gene rearrangements in the diagnosis of Hodgkin's and non-Hodgkin's lymphoma.

The results of genotypic analysis of 29 cases of malignant lymphoma are reported and the application of this technique for differentiating between Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) is evaluated. Five cases with a differential diagnosis which included HD and NHL were analysed. These results are compared with those obtained for six B-cell NHLs, nine T-cell NHLs, and nine cases of HD. This report suggests that gene rearrangement analysis is useful in some cases in which the differential diagnoses includes HD and NHL as the absence of gene rearrangements is more consistent with a diagnosis of HD than of NHL. Two monoclonal antibodies reactive with the variable region of T-cell receptor beta-chain and molecular probes to the relevant variable region genes were used to assist in the diagnosis of T-cell lymphoma. This report confirms that genotypic analysis is useful diagnostically when the results are assessed in the context of the histopathological findings.

Identification of human herpesvirus 6-specific DNA sequences in two patients with non-Hodgkin's lymphoma.

Human herpesvirus 6 (HHV-6) is a recently discovered virus which has not been causally linked to any particular disease. In order to investigate the possible role of this virus in the pathogenesis of lymphoid malignancies, we examined tissue samples from 117 patients for the presence of HHV-6-specific DNA sequences. Two cases of non-Hodgkin's lymphoma were found to be positive. One patient had a T cell lymphoma and a preceding history of angioimmunoblastic lymphadenopathy; the other had a B cell lymphoma occurring in the context of Sjögren's syndrome. HHV-6 has been isolated previously from a patient with angioimmunoblastic lymphadenopathy, and viral sequences have been identified in another patient with Sjögren's syndrome and B cell lymphoma. The relationship between HHV-6 and these conditions therefore warrants further investigation.