PubMed · 13825051
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R M FRIEDENBERG, V SAYEGH. 1960. Advanced skeletal changes in hyperparathyroidism.. https://pubmed.ncbi.nlm.nih.gov/13825051/
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Leprosy was a well-recognized and dreaded disease in Denmark in the Middle Ages (AD 1000-1536). A large fraction of the population was affected by leprosy in the 13th century. This paper analyzes the correlation between signs of leprosy and risk of dying in the small Danish village of Tirup (AD 1150-1350). Seven different dichotomous osteological lesions indicative of leprosy are analyzed, and it is possible to score at least one of these conditions on 135 skeletons of adult or adolescent people (aged 14 or more). Scores were transformed to a statistic, lambda, indicating the likelihood that the person to whom the skeleton belonged suffered from leprosy. The analyses indicate that the prevalence of leprosy among adult people in Tirup was 26% (95% confidence interval, 17-35%). The lambda statistic indicates that people who died with signs of leprosy did not differ in the distribution of age at death from those who did not have such signs. Skeletons showing dental enamel hypoplasia were less likely to come from skeletons with high lambda-values. The association between lambda and dental enamel hypoplasia indicates a relationship between stress in early childhood (ages 1-6 years) and subsequent development of signs of leprosy.
Published reports of palaeopathological analyses of skeletal collections from Central Asia are, to date, scarce. During the macroscopic examination of skeletal remains dating to the early first millennium AD from the Ustyurt Plateau, Uzbekistan, diagnostic features suggestive of leprosy were found on one individual from Devkesken 6. This adult female exhibited rhinomaxillary changes indicative of leprosy: resorption of the anterior nasal spine, rounding and widening of the nasal aperture, erosion of the alveolar margin, loss of a maxillary incisor, and inflammatory changes in the hard palate. While it is unclear whether the bones of the hands and the feet from this individual were absent as a result of collection strategy or poor preservation, lesions affecting the tibia and fibula were recorded, and the ways in which they may be related to a diagnosis of leprosy are discussed. This is the first skeletal evidence of leprosy from Central Asia and raises questions not only about the spread of the disease in the past, but also about the living conditions of what traditionally were thought of as nomadic peoples.
Although widespread skeletal dissemination is a critical step in the progression of myeloma, little is known regarding mechanisms that control metastasis of this cancer. Heparanase-1 (heparanase), an enzyme that cleaves heparan sulfate chains, is expressed at high levels in some patients with myeloma and promotes metastasis of some tumor types (eg, breast, lymphoma). Using a severe combined immunodeficient (SCID) mouse model, we demonstrate that enhanced expression of heparanase by myeloma cells dramatically up-regulates their spontaneous metastasis to bone. This occurs from primary tumors growing subcutaneously and also from primary tumors established in bone. Interestingly, tumors formed by subcutaneous injection of cells metastasize not only to bone, but also to other sites including spleen, liver, and lung. In contrast, tumors formed by injection of cells directly into bone exhibit a restricted pattern of metastasis that includes dissemination of tumor to other bones but not to extramedullary sites. In addition, expression of heparanase by myeloma cells (1) accelerates the initial growth of the primary tumor, (2) increases whole-body tumor burden as compared with controls, and (3) enhances both the number and size of microvessels within the primary tumor. These studies describe a novel experimental animal model for examining the spontaneous metastasis of bone-homing tumors and indicate that heparanase is a critical determinant of myeloma dissemination and growth in vivo.