Guglielmo di Conches e il Dragmaticon philosophiae

2013 - 2014This dissertation about William of Conches and the Dragmaticon Philosophiae is divided into two sections. The aim of the first section is to reconstruct the life and the literary works of one of the most important teachers of Chartres of the twelfth century. The aim of the second section is to analyse his most important work, written between 1146 and 1149, after undergoing a noteworthy process of rethinking, reorganization and enlargement of his youthful work, called Philosophia, which had been bitterly attacked by the cistercian monk William of Saint-Thierry, who denounced its serious theological errors in 1140 or 1141. The enquiry about the life of William of Conches, to which the first chapter is dedicated, has produced some interesting results, which seem to open new areas of research, especially regarding the philosopher’s place of birth (which may not well be Conches, but Saint-Martin du Tilleul) and the last phase of his life, which could have ended in England at the court of Henry II (to whom William was tutor during the writing of the Dragmaticon), or in Paris as magister scholae. The enquiry about the literary works of William of Conches, to which the second chapter is dedicated, deals with a detailed presentation of the historiographical debate, that has so far led to the identification of the works currently attributed to the philosopher. The first part of the third chapter is devoted to the analysis of the accusations, with which William of Saint-Thierry attacked the teacher of Chartres in his De erroribus Guillelmi de Conchis, and to the verification of their legitimacy. The second part instead is dedicated to the description of the Dragmaticon’ structure and the novelties of this work with respect to Philosophia, the presentation of the Dragmaticon’ s purpose, thus the tractatus de substantiis, and the description of the research method used. With respect to the latter, William of Conches claims to conduct his research philosophice, in accordance with the typical approach of philosophers, who deal with universals expressing themselves through rationes necessariae, but when he investigates the substances of the physical world, he cannot always argue philosophice about them because of their mutability, and must sometimes argue dialectice, in accordance with the typical approach of dialecticians, who deal with particulars expressing themselves through rationes verisimiles. 2 The fourth chapter is devoted to the presentation of William’s definition of substance as res per se existens and to the description of the species of substance in the order in which William presents them in the Dragmaticon. After he speaks about God and the angels expressing himself through rationes necessariae derived from faith, he then deals with the elements. In the Dragmaticon William defines element as what is first in the composition and last in the resolution of the body and describes it as a body that is invisible, imperceptible and unextended per se. The feature of unextention attribuited to elementary bodies gives them a paradoxical ontological status, as there are no bodies devoid of the three dimensions of space. But the paradoxicalness of this description stems from the fact that in the Dragmaticon William describes element from the point of view of philosophers, who speak about universals expressing themselves through rationes necessariae. According to philosophers element is a body without dimension, because it is not a physical being, but a metaphyisical one, that is an abstract form similar to a geometric point. The philosopher then can only postulate the existence of beings, which are first in the composition and last in the resolution of the body, but he cannot prove their existence in re. However, it is from the fact that postulating the existence of simple and minimal particles of the bodies is more rational than not postulating it, that can stem the existence in re of these particles. The fifth chapter is devoted to the distinction between opus creatoris and opus naturae. God creates simultaneously all elements ex nichilo, mixed in a big body mass, so as to occupy all the existent room. The following exornatio mundi, which is the correct and balanced disposition of the elements in the world and the formation of the bodies of living creatures, concerns nature, a kind of ordering principle inside the elements, which God uses to produce the same from the same in the world. In the exornatio mundi nature operates within the concept of the same from the same, when it drives the elements to their cosmic place. In an already formed world nature operates the same from the same, when it initiates physiological mechanisms (like generation and formation of bodies, nutrition, appetition, ritention, digestion, expulsion, growth and sleep) typical of an organic structure. The sixth chapter deals with the description of the works of nature in the world through the analysis of the main macrocosmic phenomena, which take place in the four elementa mundi. The seventh chapter is devoted to the description of the operations in the human body which depend on nature, and of those that do not depend on nature, but on the soul. 3 Some of the operations that depend on the soul (like breathing, sense, imagination and voluntary motion) are common to animals and men. Some others (like wit, memory, opinion, reason and intelligence) are common to men and divine spirits. The animal soul is mortal and develops spontaneously in an organic body, whereas the human soul is a separate and immortal substance. It’s created directly by God and joins the body without changing its physical nature and takes its course by means of a very fine airy substance, that arises from the liver, goes through the heart, where it causes breath, and arrives in the brain after two refining phases. [edited by Author]XIII n.s

Opposite Response to Vitamin K Antagonists: A Report of Two Cases and Systematic Review of Literature

Vitamin K antagonists (VKAs) are used in the prophylaxis and treatment of thromboembolic disorders. Despite a high efficacy, their narrow therapeutic window and high response variability hamper their management. Several patients experience fluctuations in dose–response and are at increased risk of over- or under-anticoagulation. Therefore, it is essential to monitor the prothrombin time/international normalized ratio to determine the so-called stable dose and to adjust the dosage accordingly. Three polymorphisms, CYP2C9∗2, CYP2C9∗3 and VKORC1-1639G>A, are associated with increased sensitivity to VKAs. Other polymorphisms are associated with a request for a higher dose and VKA resistance. We described the clinical cases of two patients who were referred to the Clinical Pharmacology and Pharmacogenetics Unit of the University Hospital of Salerno for pharmacological counseling. One of them showed hypersensitivity and the other one was resistant to VKAs. A systematic review was performed to identify randomized clinical trials investigating the impact of pharmacogenetic testing on increased sensitivity and resistance to VKAs. Although international guidelines are available and information on the genotype-guided dosing approach has been included in VKA drug labels, VKA pharmacogenetic testing is not commonly required. The clinical cases and the results of the systematically reviewed RCTs demonstrate that the pharmacogenetic-based VKA dosing model represents a valuable resource for reducing VKA-associated adverse events

Three Cases of Long-Lasting Tumor Control with Erlotinib after Progression with Gefitinib in Advanced Non-Small Cell Lung Cancer

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Retroperitoneoscopic Varicocelectomy in Adolescents: Long-term Follow-up in Two Italian Centres

Background: The varicocele is the most commonly diagnosed pre-pubertal andrological condition with an incidence of 10%-15% between adolescents. The aim of this study was to evaluate the efficacy of retroperitoneoscopic varicocelectomy (RV) in two Italian centres with particular attention to post-operative testicular volume and semen analysis after 18 years of life. Materials and Methods: From 1999 to 2010, 286 adolescents underwent retroperitoneoscopic left varicocelectomy. Of these patients, 67 were evaluated by clinical examination, ultrasound and semen analysis, allowing an adequate long-term follow-up. Results: Surgery was performed at a mean age of 13 years (range 10-17) without intraoperative complications. There were two recurrences (3%), two left testis hypotrophy (3%) and four hydroceles (6%), not yet undergone surgery because asymptomatic or without tension. Currently, 44 patients accepted to perform semen analysis which showed a reduction in sperm motility in 12 cases, with associated morphological alterations in 3 and reducing number of spermatozoa in one case. Conclusions: In consideration of morphological and biomolecular spermatic alterations reported in adolescent varicocele that could interfere with cellular migration, differentiation and nutrition, it is fundamental to consider the correction of varicocele, not only for the classical indications, but also as a choice for arresting the progressive damage that inevitably acts for several years on the adolescent testis. The RV in adolescents is a safe and feasible procedure for experienced paediatric laparoscopic surgeons with early good clinical outcomes, but more studies occur to understand the real impact of adolescent varicocelectomy on testicular function

Assessment of DNA Damage by RAPD in Paracentrotus lividus Embryos Exposed to Amniotic Fluid from Residents Living Close to Waste Landfill Sites

The aim of this study was to assess the genotoxic effects of environmental chemicals on residents living near landfills. The study was based on samples of amniotic fluid from women living in the intensely polluted areas around the Campania region of Italy compared to a nonexposed control group. We evaluated the genetic effects that this amniotic fluids collected in contaminated sites had on Paracentrotus lividus embryos. DNA damage was detected through changes in RAPD (Random Amplified Polymorphism DNA) profiles. The absence of the amplified DNA fragments indicated deletions in Paracentrotus lividus DNA exposed to the contaminated amniotic fluids when compared to equal exposure to uncontaminated fluids. These results show the ability of RAPD-PCR to detect and isolate DNA sequences representing genetic alterations induced in P. lividus embryos. Using this method, we identified two candidate target regions for DNA alterations in the genome of P. lividus. Our research indicates that RAPD-PCR in P. lividus embryo DNA can provide a molecular approach for studying DNA damage from pollutants that can impact human health. To our knowledge, this is the first time that assessment of DNA damage in P. lividus embryos has been tested using the RAPD strategy after exposure to amniotic fluid from residents near waste landfill sites

The Renaissance of KRAS Targeting in Advanced Non-Small-Cell Lung Cancer: New Opportunities Following Old Failures

: Non-small cell lung cancer (NSCLC) represents the perfect paradigm of 'precision medicine' due to its complex intratumoral heterogeneity. It is truly characterized by a range of molecular alterations that can deeply influence the natural history of this disease. Several molecular alterations have been found over time, paving the road to biomarker-driven therapy and radically changing the prognosis of 'oncogene addicted' NSCLC patients. Kirsten rat sarcoma (KRAS) mutations are present in up to 30% of NSCLC (especially in adenocarcinoma histotype) and have been identified decades ago. Since its discovery, its molecular characteristics and its marked affinity to a specific substrate have led to define KRAS as an undruggable alteration. Despite that, many attempts have been made to develop drugs capable of targeting KRAS signaling but, until a few years ago, these efforts have been unsuccessful. Comprehensive genomic profiling and wide-spectrum analysis of genetic alterations have only recently allowed to identify different types of KRAS mutations. This tricky step has finally opened new frontiers in the treatment approach of KRAS-mutant patients and might hopefully increase their prognosis and quality of life. In this review, we aim to highlight the most interesting aspects of (epi)genetic KRAS features, hoping to light the way to the state of art of targeting KRAS in NSCLC

Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: A restrospective analysis from the ObservEr study

Abstract Objectives The influence of age ( KRAS wild type (WT) metastatic colorectal cancer (mCRC). Methods 225 patients of the Observed study (PS 0-1) were retrieved based on age ( Results The two patient groups (141  p  = 0.002), which is likely due to higher proportions of metastatic resection (27.0% vs 8.3%; p  = 0.001) and utilization of second-line therapy in younger group (58.9% vs 42.9%; p  = 0.028). Conclusion The current data suggest that fit older patients with mCRC can be safely treated with a cetuximab-based therapy, as QoL and safety profile do not seem to be affected by age. In addition, age did not impact the choice of chemotherapy to be associated to cetuximab and treatment compliance

PTEN Loss as a Predictor of Tumor Heterogeneity and Poor Prognosis in Patients With EGFR-mutant Advanced Non-small-cell Lung Cancer Receiving Tyrosine Kinase Inhibitors

Background: Rapid disease progression of patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) has been recently associated with tumor heterogeneity, which may be mirrored by coexisting concomitant alterations. The aim of this analysis was to investigate the correlation between loss of function of PTEN and the efficacy of tyrosine kinase inhibitors in this population. Materials and Methods: Archival tumor blocks from patients with EGFR-mutant NSCLC who were administered upfront tyrosine kinase inhibitors were retrospectively collected. The status of 4 genes (PTEN, TP53, c-MET, IGFR) was evaluated by immunohistochemistry, and it was correlated with overall response rate, overall survival (OS), and progression-free survival (PFS). Results: Fifty-one patients were included. In multivariate analysis, PTEN loss (hazard ratio [HR], 3.46; 95% confidence interval [CI], 1.56-7.66; P = .002), IGFR overexpression (HR, 2.22; 95% CI, 1.03-4.77; P = .04), liver metastases (HR, 3.55; 95% CI, 1.46-8.65; P = .005), and Eastern Cooperative Oncology Group performance status (ECOG PS) > 1 (HR, 2.57; 95% CI, 1.04-6.34; P = .04) were significantly associated with shorter PFS. Patients with PTEN loss had a median PFS of 6 months (2-year PFS, 11.6%), whereas patients without PTEN loss had a median PFS of 18 months (2-year PFS, 43.6%) (log-rank P < .005). In the multivariate analysis, PTEN loss (HR, 5.92; 95% CI, 2.37-14.81; P < .005), liver metastases (HR, 2.63; 95% CI, 1.06-6.51; P = .037), and ECOG PS > 1 (HR, 2.80; 95% CI, 1.15-6.81; P = .024) were significantly associated with shorter OS. Patients with PTEN loss had a median OS of 6 months (2-year OS, 12.2%), whereas in patients without PTEN loss, OS was not reached (2-year OS, 63.9%) (log-rank P < .0005).Conclusions: A low-cost and reproducible immunohistochemistry assay for PTEN loss analysis represents a potential tool for identifying tumor heterogeneity in patients with advanced EGFR-mutant NSCLC