Our findings support the contention of a complex pathogenesis of NAION resulting from the coincidence of proatherogenic, prothrombotic and proinflammatory processes. The alterations described could be causative, side effects, or just coincidental findings.
Background: The aim of our present study was to examine the risk factors for atherosclerosis as well as thrombophilic risk factors for their role in patients with NAION in comparison to healthy controls. Methods: Prospective case-control-design with 109 Patients and 109 age-and sex-matched healthy controls. Results: Elevated levels of fibrinogen, FVIII:C, FIX:C, FXI:C, plasminogen activity, von Willebrand antigen (vWF:Ag) and activity, triglycerides, elevated erythrocyte sedimentation rate and decreased levels of high density lipoprotein (HDL) proved to be significant risk factors associated with NAION (OR 1.9 to 5.4; p<0.05). The combination of these risk determinants further increased the risk in a multiplicative or supra-multiplicative way (up to OR 16.5; p<0.0001). None of the examined genetic risk factors (factor V Leiden mutation, Prothrombin mutation, platelet polymorphisms KOZAK and VNTR of glycoprotein 1bα, Hpa-1 polymorphism of GPIIb-IIIa, C807T polymorphism of GPIa/IIa, 4G/5G polymorphism of PAI-1 and C667T mutation of MTHFR gene) was significantly associated with the disease. However, when the HPA-1b allele, GPIa807T allele or the PAI-1 polymorphism were combined with increased levels of fibrinogen or vWF:Ag, a significant interaction with a supra-multiplicative increase in risk could be demonstrated. Conclusions: In this first comprehensive analysis of a wide range of risk determinants of atherosclerosis and thrombophilia in NAION patients, several risk factors could be identified and quantified. Risk factors of arterial thrombosis appear to interact with risk factors of inflammatory atherosclerosis triggering NAION.
We investigated the oestrogen-receptor content (ER-ICA) of 614 tissue samples taken from breast carcinomas (all obtained from patients at the Universitäts-Frauenklinik, Mainz FRG) using immunohistochemical procedures. Since the findings of follow-up studies as well as estimates of survival probability (according to the procedure of Kaplan-Meier) for 334 of the primary breast carcinomas were available, it was possible, to assess the prognostic value of the immunohistochemical results. The percentage of receptor-positive tumour cell nuclei (i.e. the heterogeneity of the tumour), as opposed to the staining intensity, proved to be the most useful criterion of the IRS, whose cut off level was determined as being IRS 1. Regardless of their lymph node status, mammary carcinomas which were immunohistochemically positive for estrogen receptors, were found to have a significantly better short-term prognosis, than breast tumours which were negative for such receptors. In the case of certain breast carcinomas exhibiting contradictory findings (i.e. ER-ICA positive but biochemically negative for oestrogen receptors), the present immunohistochemical method provided the most accurate assessment of the biological behaviour and development of the tumor. Therefore, ER-ICA represents a valuable prognostic criterion, which when complemented with PR-ICA, should facilitate attaining optimal selection of patients suitable for endocrine therapy.
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