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We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here we asked whether this bias is mediated by the non conscious selection of nuclei that "match the expectation" induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists each carcinoma was shown twice once before a background of a low grade tubule rich carcinoma and once before the background of a high grade solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger darker and more irregular nuclei when those were projected before kigh grade solid carcinomas than before low grade tubule rich carcinomas (and vice versa). However the morphometric differences of the selected nuclei accounted for only 11 of the architecture induced bias suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that "match the expectation". In conclusion selection of « matching nuclei » represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture.

We recently reported that nuclear grading in prostate cancer is subject to a strong confirmation bias induced by the tumor architecture. We now wondered whether a similar bias governs nuclear grading in breast carcinoma. An unannounced test was performed at a pathology conference. Pathologists were asked to grade nuclei in a PowerPoint presentation. Circular high power fields of 27 invasive ductal carcinomas were shown superimposed over low power background images of either tubule rich or tubule poor carcinomas. We found (a) that diagnostic reproducibility of nuclear grades was poor to moderate (weighed kappa values between 0.07 and 0.54 27 cases 44 graders) but (b) that nuclear grades were not affected by the tumor architecture. We speculate that the categorized grading in breast cancer separating tubule formation nuclear pleomorphism and mitotic figure counts in a combined three tier score prevents the bias that architecture exerts on nuclear grades in less well controlled situations.

The genetic mucopolysaccharidosis syndromes (MPS) are autosomal recessive inborn errors of metabolism. Heart valve involvement in MPS is not uncommon but only a few case reports of successful cardiac surgery are available. In particular, reports of combined aortic and mitral stenosis associated with MPS type I-S are very rare. Both type I and type VI MPS are associated with significant left sided valvar heart disease that requires surgical valve replacement because of irregular valve thickening, fibrosis, and calcification. A 35 year old man had severe mitral valve stenosis after successful surgical replacement of a stenotic aortic valve. Valvar heart disease was investigated by cardiac ultrasound and left heart catheterisation. Histomorphological characterisation of the affected mitral valve was performed. The case illustrates typically associated clinical features of cardiac and extracardiac abnormalities found in MPS type I-S. Keywords: valvar disease; mucopolysaccharidosis; mitral valve stenosis; aortic valve stenosis

OBJECTIVE The clinical complications of extracorporeal circulation (ECC) have been linked to a systemic activation of cellular and humoral components and to a dysregulation of the microcirculatory compartment. Since to date only in vitro methods exist for evaluation, we developed an animal model to study the effects of ECC on the microcirculation. To establish the model, we assessed whether these effects are dependent on the duration of ECC. METHODS Intravital fluorescence microscopy was used on the dorsal skinfold chamber preparation in chronically instrumented, awake Syrian golden hamsters. ECC was realized using a micro-rollerpump and a silicon tube shunting blood between the carotid artery and the jugular vein. ECC was performed in three groups for various times (2, 10 and 20 min) after application of heparin at 300 IU/kg body wt. In hamsters, the application of high-dose heparin releases endothelial bound superoxide dismutase (SOD), a natural scavenger of oxygen-derived free radicals. Protocol II assigned two groups receiving heparin at different doses of 50 and 2000 IU/kg body wt. RESULTS ECC for 2 min served as control to exclude effects from hemodilution and resulted in a minimal induction of leukocyte/endothelial cell interaction. Isovolemic ECC for 20 min resulted in an increase in rolling (from 11 +/- 3 to 38 +/- 20%, mean +/- S.D., P < 0.05) and adherent leukocytes (from 19 +/- 16 to 215 +/- 145 cells/mm2, mean +/- S.D., P < 0.05) in postcapillary venules. Microhemodynamic parameters and functional capillary density were not significantly affected. Arterial blood pressure and heart rate were stable. Heparin at 2000 IU/kg inhibited post-ECC leukocyte adhesion following ECC, whereas 50 IU/kg showed no protective effects. CONCLUSIONS Leukocyte/endothelial cell interaction, induced by blood contact with synthetic surfaces, was directly visualized in vivo. The number of adherent leukocytes was dependent on the duration of ECC. The application of high-dose heparin followed by release of SOD almost prevented leukocyte activation, suggesting a formation of oxygen free radicals during ECC. The new application of the hamster model may allow to study the underlying pathomechanisms and to develop therapeutic/prophylactic strategies to avert problems associated with ECC.

The case of a Moroccan woman, age 25, who came into the emergency department with clinical tetany, is presented. She had experienced muscle spasms and paresthaesia of the upper limb over the previous few days. She had also experienced major diarrhoea for the previous 3 weeks. Investigations revealed a severe electrolyte disorder.