Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view

Introduction

Mammographic density is known to be a strong risk factor for breast cancer. A particularly strong association with risk has been observed when density is measured using interactive threshold software. This, however, is a labour-intensive process for large-scale studies.

Methods

Our aim was to determine the performance of visually assessed percent breast density as an indicator of breast cancer risk. We compared the effect on risk of density as measured with the mediolateral oblique view only versus that estimated as the average density from the mediolateral oblique view and the craniocaudal view. Density was assessed using a visual analogue scale in 10,048 screening mammograms, including 311 breast cancer cases diagnosed at that screening episode or within the following 6 years.

Results

Where only the mediolateral oblique view was available, there was a modest effect of breast density on risk with an odds ratio for the 76% to 100% density relative to 0% to 25% of 1.51 (95% confidence interval 0.71 to 3.18). When two views were available, there was a considerably stronger association, with the corresponding odds ratio being 6.77 (95% confidence interval 2.75 to 16.67).

Conclusion

This indicates that a substantial amount of information on risk from percentage breast density is contained in the second view. It also suggests that visually assessed breast density has predictive potential for breast cancer risk comparable to that of density measured using the interactive threshold software when two views are available. This observation needs to be confirmed by studies applying the different measurement methods to the same individuals.     

Absence of alternative splicing in bcr-abl mRNA in chronic myeloid leukemia cell lines

The major consequence of the Philadelphia (Ph) translocation in chronic myeloid leukemia (CML) is the formation of a bcr-abl hybrid oncogene encoding a tumor cell-specific protein P210bcr-abl. In contrast to this, in Ph chromosome-positive acute lymphoblastic leukemia (Ph + ALL), a P190bcr-abl can be observed. This P190bcr-abl has been implicated in acute rather than chronic leukemogenesis. Therefore, it can be hypothesized that the transition from chronic to blast phase in CML is accompanied by an alternative splice in the bcr-abl mRNA, which results in a switch of the production of P210bcr-abl into P190bcr-abl. Initial S1 nuclease protection mapping supported this theory. However, this result appears to be based on an artifact in the S1 analysis. By using the polymerase chain reaction we provide evidence for the absence of alternative splicing in bcr-abl mRNA in two CML blast crisis cell lines.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Serotonin metabolism in cluster headache

Despite some evidence of the involvement of the serotonergic system in cluster headache (CH) pathophysiology, the serotonin (5HT) metabolism has so far been poorly studied. The aim of this study was to investigate plasma and platelet levels of 5HT and 5-hydroxyindoleacetic acid (5HIAA) in CH patients in the active period of the disease. Nineteen CH sufferers and 17 sex- and age-matched healthy controls were studied. CH patients showed significantly higher plasma levels of 5HT and 5HIAA compared to controls (5HT: 5.7±6.1 ng/ml vs 0.2±0.2 ng/ml; p =0.02; 5HIAA: 34.7±46.1 ng/ml vs 0.6±0.7 ng/ml; p =0.004). In platelet 5HT levels were slightly reduced in CH patients in comparison with those of control subjects (662.4±522.3 ng/10⁻⁸ platelets vs 832.1±587.9 ng/10⁻⁸ platelets; n.s.) and 5HIAA levels resulted significantly lower in CH sufferers than in control subjects (3.2±2.6 ng/10⁻⁸ platelets vs 6.7±4.8 ng/10⁻⁸ platelets; p =0.04). Our data suggest that CH is characterized by an increase of plasma serotonergic metabolism that could reflect an involvement of the central serotonergic system in the pathogenesis of CH.     

Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus

Increased emphasis on strict glycaemic control of insulin dependent diabetes mellitus (IDDM) in young patients may be expected to cause increases in rates of significant hypoglycaemia. To evaluate whether this is the case for a large population based sample of IDDM children and adolescents rates of severe (coma, convulsion) and moderate (requiring assistance for treatment) hypoglycaemia were studied prospectively over a four year period. A total of 709 patients were studied yielding 2027 patient years of data (mean (SD) age: 12.3 (4.4); range 0-18 years, duration IDDM: 4.9 (3.8) years). Details of hypoglycaemia were recorded at clinic visits every three months when glycated haemoglobin (HbA1c) was also measured. Overall the incidence of severe hypoglycaemia was 7.8 and moderate was 15.4 episodes/100 patient years. Over the four years mean (SD) clinic HbA1c steadily fell from 10.2 (1.6)% in 1992 to 8.8 (1.5)% in 1995. In parallel with this there was a dramatic increase in the rate of hypoglycaemia, especially in the fourth year of the study, when severe hypoglycaemia increased from 4.8 to 15.6 episodes/100 patient years. This increase was particularly marked in younger children (< 6 years) in whom severe hypoglycaemia increased from 14.9 to 42.1 episodes/100 patient years in 1995. It is concluded that attempts to achieve improved metabolic control must be accompanied by efforts to minimise the effects of significant hypoglycaemia, particularly in the younger age group.     

Impact of nasopharyngeal swab types on detection of Bordetella pertussis by PCR and culture

A study was designed to assess the performance of various swabs and transport media routinely used to collect specimens submitted for Bordetella culture and PCR. Calcium-alginate swabs inhibited the PCR. No inhibition was detected in any PCRs with dacron or rayon swabs. All swab materials performed similarly for recovery of Bordetella pertussis in culture. The Amies with charcoal transport system performed poorly for culture. Calcium-alginate swabs are not recommended for PCR-based detection of B. pertussis. Dacron and rayon swabs are an excellent choice for both PCR and culture.