Luciana Rita Angeletti

Gene-environment interactions in the pre-Industrial Era: The cancer of King Ferrante i of Aragon (1431-1494)

King Ferrante I of Aragon, leading figure of the Italian Renaissance, died in 1494. The autopsy of his mummy revealed a tumor infiltrating the small pelvis. We examined the histologic and molecular features of this ancient tumor to investigate its primary origin. Hematoxylin-eosin, Van Gieson, and Alcian Blue staining showed neoplastic cells infiltrating muscular fibers and forming pseudo-glandular lumina disseminated in fibrous stroma with scarce mucus. A strong immunoreactivity of the neoplastic cells was shown for pancytokeratins and proliferating cell nuclear antigen. Molecular fingerprints were investigated by examining K-ras, BRAF, and microsatellite instability in ancient tumor DNA. Sequencing analysis showed G-to-A transition in codon 12 of K-ras. BRAF mutations and microsatellite instability were not observed. Because the presence of K-ras codon 12 mutation could be associated with exposure to chemical carcinogens, possibly present in some food items, paleodietary reconstruction of the King Ferrante I was carried out by carbon (δ(13)C ) and nitrogen (δ(15)N) stable isotopes analysis. δ(13)C and δ(15)N values found in bone collagen of the King were consistent with a massive intake of animal proteins. Overall, our data show that the tumor of Ferrante I was a mucinous adenocarcinoma with molecular fingerprints characteristic of colorectal carcinogenesis linked to K-ras pathway. Paleodietary reconstruction and historical chronicles indicate a strong consumption of meat by the King. The possible abundance of dietary carcinogens, related to meat consumption, could explain the K-ras mutation causing the colorectal tumor that killed Ferrante I more than 5 centuries ago.

The Perì ouron Treatise of Stephanus of Athens: Byzantine Uroscopy of the 6th-7th Centuries AD

In the 6th-7th centuries AD, treatises on uroscopy were written by Theophilus, Magnus and the author of work transmitted through the ms. Parisinus gr. 2260, Stephanus of Athens. These works are the first to deal comprehensively with the problem of urines, uroscopy and their clinical role, so that a philological and content analysis and examination of their reciprocal relationships may clarify an important period in the birth and development of Byzantine uroscopy, which represents a significant epistemological passage in the medieval history of medicine (e.g. the positing of relationships between physical signs and systemic diseases).

A subject with abnormally short stature from Imperial Rome

In spite of the rich iconographic and literary documentation from ancient sources, the skeletal evidence concerning individuals of abnormally short stature in the Greco-Roman world is scarce. The necropolis of Viale della Serenissima/Via Basiliano in Rome, mostly referable to the II century AD, recently yielded the skeleton of an individual characterized by proportionate short stature, gracile features suggesting female gender, and delayed epiphysial closure, associated with full maturation of the permanent dentition. These characteristics could be compatible with the phenotype associated with female gonadal dysgenesis. The skeletal individual described here, although poorly preserved, represents the first evidence of a paleopathologic condition affecting skeletal growth documented for the population of ancient Rome.

Theophilus’ Auctoritas: The Role of De urinis in the Medical Curriculum of the 12th–13th Centuries

The three principles to know, to know how and to know how to be are already condensed in the works of Theophilos (7th–9th centuries). Theophilus’ De urinis was included in Latin translation in the Articella, probably because of its intermediate position between the texts of high doctrinal value by Hippocrates and Galen (lacking, however, a unifying ‘theory of urine’) and the epitomes, short manuals without any theoretical background. It thus forms an excellent synthesis of a cultural approach reconciling iatrosophia and techne and offers to the reader a text reconciling the theory and the practice, useful to health workers in hospitals, novice beginners and medical scholars. Thanks to his strong attention to the correlation between symptoms and pathology and to his search for assessment scales, Theophilus became the author on whom the birth of medical medieval studies was founded.