Natural History and Outcome of Hepatic Vascular Malformations in a Large Cohort of Patients with Hereditary Hemorrhagic Teleangiectasia

BACKGROUND: Hereditary hemorrhagic telangiectasia is a genetic disease characterized by teleangiectasias involving virtually every organ. There are limited data in the literature regarding the natural history of liver vascular malformations in hemorrhagic telangiectasia and their associated morbidity and mortality. AIM: This prospective cohort study sought to assess the outcome of liver involvement in hereditary hemorrhagic telangiectasia patients. METHODS: We analyzed 16 years of surveillance data from a tertiary hereditary hemorrhagic telangiectasia referral center in Italy. We considered for inclusion in this study 502 consecutive Italian patients at risk of hereditary hemorrhagic telangiectasia who presented at the hereditary hemorrhagic telangiectasia referral center and underwent a multidisciplinary screening protocol for the diagnosis of hereditary hemorrhagic telangiectasia. Of the 502 individuals assessed in the center, 154 had hepatic vascular malformations and were the subject of the study; 198 patients with hereditary hemorrhagic telangiectasia and without hepatic vascular malformations were the controls. Additionally, we report the response to treatment of patients with complicated hepatic vascular malformations. RESULTS: The 154 patients were included and followed for a median period of 44 months (range 12-181); of these, eight (5.2%) died from VM-related complications and 39 (25.3%) experienced complications. The average incidence rates of death and complications were 1.1 and 3.6 per 100 person-years, respectively. The median overall survival and event-free survival after diagnosis were 175 and 90 months, respectively. The rate of complete response to therapy was 63%. CONCLUSIONS: This study shows that substantial morbidity and mortality are associated with liver vascular malformations in hereditary hemorrhagic telangiectasia patients

The role of clinical and neuroimaging features in the diagnosis of CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. METHODS: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. RESULTS: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. CONCLUSIONS: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.The Lombardia GENS project has received funding from the Regione Lombardia Government as a Research Independent Project (DGR n°VIII/006128-12/12/2007). Lombardia GENS is an investigator-driven, academic, non-profit consortium and is publicly funded. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by the Cambridge University Hospitals NIHR Biomedical Research Centr

Felsefenin Doğuşu Felsefe Akımları

Burada karşıtların birliği söz konusudur ve bu birlik Tanrı’nın, gizlinin ve bilgeliğin, dünyanın temel aktarımlarıdır. Böyle bir temel aşkındır. Bunlar Tanrı’nın, gizli olanın an- latımıdır (s. 56–57). Yazar, burada bir sorunu ortaya koymaktadır; “Eğer Yunan bilgeliğinin kökeni Mani’de Pythiacı kendinden geçişte, gizemli ve gizemci deneyimde bulunuyorsa, o halde, bu dinsel arka plandan soyut, akılcı bir düşünceye geçiş nasıl açıklanabilir?” Ayrıca bu bilginler çağının gelişmiş aşamasında, düzenlenmiş, söze dökülmüş bir akıl, basit olmayan bir mantık, önemli düzeyde bir kuramsal gelişme de buluruz. Yazarın de- ğerlendirmesine göre bütün bunları olanaklı kılan diyalektik olmuştur. Buradaki diyalektik modern anlamında değil, iki ya da daha çok canlı in- san arasında geçen gerçek bir tartışma ve tartışma sanatı anlamında kulla- nılmıştır. Bu bağlamda diyalektik Yunan kültürünün en dikkate değer en özgün görüngülerinden biridir (s. 61). Yazara göre Yunan tartışmasının kurtuluşunda yıkıcı bir amaç ve böyle bir amacın diyalektik tarafından gerçekleştirilmesi vardır. Yani ileri sürülen bir sav her iki yönde de ispatla- nabili

Eraclito /

Includes bibliographical references and indexes