Variable size computer-aided detection prompts and mammography film reader decisions

Introduction

The purpose of the present study was to investigate the effect of computer-aided detection (CAD) prompts on reader behaviour in a large sample of breast screening mammograms by analysing the relationship of the presence and size of prompts to the recall decision.

Methods

Local research ethics committee approval was obtained; informed consent was not required. Mammograms were obtained from women attending routine mammography at two breast screening centres in 1996. Films, previously double read, were re-read by a different reader using CAD. The study material included 315 cancer cases comprising all screen-detected cancer cases, all subsequent interval cancers and 861 normal cases randomly selected from 10,267 cases. Ground truth data were used to assess the efficacy of CAD prompting. Associations between prompt attributes and tumour features or reader recall decisions were assessed by chi-squared tests.

Results

There was a highly significant relationship between prompting and a decision to recall for cancer cases and for a random sample of normal cases (P < 0.001). Sixty-four per cent of all cases contained at least one CAD prompt. In cancer cases, larger prompts were more likely to be recalled (P = 0.02) for masses but there was no such association for calcifications (P = 0.9). In a random sample of 861 normal cases, larger prompts were more likely to be recalled (P = 0.02) for both mass and calcification prompts. Significant associations were observed with prompting and breast density (p = 0.009) for cancer cases but not for normal cases (P = 0.05).

Conclusions

For both normal cases and cancer cases, prompted mammograms were more likely to be recalled and the prompt size was also associated with a recall decision.     

Noninfectious interstitial lung disease during infliximab therapy: Case report and literature review

Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases.However,lung toxicity can be induced by conventional medications used to maintain remission,and similar evidence is also emerging for biologics.We present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab.She was referred to our clinic with a severe relapse and was treated with infliximab,an antitumor necrosis factor α(TNF-α)antibody,to induce remission.After an initial benefit,with decreases in bowel movements,rectal bleeding and C-reactive protein levels,she experienced shortness of breath after the 5thinfusion.Noninfectious interstitial lung disease was diagnosed.Both mesalamine and infliximab were discontinued,and steroids were introduced with slow but progressive improvement of symptoms,radiology and functional tests.This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations.Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases,this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.     

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.      

Monocytes stimulate fibroblastoid bone marrow stromal cells to produce multilineage hematopoietic growth factors

In previous studies we have found that monocytes produce soluble factors that stimulate human umbilical vein endothelial cells to produce granulocyte-macrophage colony-stimulating activity (CSA), burst- promoting activity (BPA), and megakaryocyte colony-stimulating activity (Meg-CSA) as well as factors that stimulate T lymphocytes and neonatal fibroblasts to produce CSA. To test the hypothesis that monocytes would similarly stimulate the production of hematopoietic growth factors by autologous bone marrow stromal cells, multiply-passaged adherent fibroblastoid cells derived from the bone marrow of normal volunteers were exposed to conditioned media prepared by incubating autologous peripheral blood monocytes in complete medium for three days. When conditioned media from stromal cells incubated in monocyte-conditioned medium were compared with those of stromal cells cultured in the absence of monocyte-conditioned medium, BPA was increased fourfold and CSA was increased more than 30-fold. We conclude that mononuclear phagocytes recruit stromal cells of the marrow to produce multilineage growth factors in vitro. We suggest that these monocyte-derived recruiting activities may play an important role in orchestration of hematopoietic growth factor production by cells of the marrow microenvironment.     

Antihypertensive activity of indolepyruvic acid: a keto analogue of tryptophan.

We studied the effect of indole-3-pyruvic acid (IPA) on systolic blood pressure of normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats. Experiments were also carried out in order to investigate whether IPA may influence the development of hypertension in spontaneously hypertensive rats. Age-matched normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats treated with N-methylglucamine, were used as controls. Acute oral (up to 50 mg/kg) and intravenous (5 mg/kg) administration of IPA did not change systolic blood pressure in any models of hypertension. By contrast, a repeated administration of IPA (100 mg/kg/day, by oral gavage for 10 days) significantly decreased systolic blood pressure in all models of hypertension, while it elicited no significant effect in normotensive rats. Moreover, when IPA was given daily to 5-week-old spontaneously hypertensive rats for 7 weeks, it partially inhibited the development of hypertension. In addition, chronic administration of IPA caused enhanced levels of tryptophan and 5-hydroxyindoleacetic acid in the cortex and diencephalon. Brainstem serotonin content in both normotensive and spontaneously hypertensive rats was also enhanced by IPA treatment. Our results suggest that IPA lowers blood pressure in different rat models of hypertension and this effect seems to be correlated with an increase in cerebral serotonin metabolism.     

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.