Pathophysiology of anemia and erythrocytosis.

An increasing understanding of the process of erythropoiesis raises some interesting questions about the pathophysiology, diagnosis and treatment of anemia and erythrocytosis. The mechanisms underlying the development of many of the erythrocytoses, previously characterised as idiopathic, have been elucidated leading to an increased understanding of oxygen homeostasis. Characterisation of anemia and erythrocytosis in relation to serum erythropoietin levels can be a useful addition to clinical diagnostic criteria and provide a rationale for treatment with erythropoiesis stimulating agents (ESAs). Recombinant human erythropoietin as well as other ESAs are now widely used to treat anemias associated with a range of conditions, including chronic kidney disease, chronic inflammatory disorders and cancer. There is also heightened awareness of the potential abuse of ESAs to boost athletic performance in competitive sport. The discovery of erythropoietin receptors outside of the erythropoietic compartment may herald future applications for ESAs in the management of neurological and cardiac diseases. The current controversy concerning optimal hemoglobin levels in chronic kidney disease patients treated with ESAs and the potential negative clinical outcomes of ESA treatment in cancer reinforces the need for cautious evaluation of the pleiotropic effects of ESAs in non-erythroid tissues.

The death blow to unlimited liability in Victorian Britain: The City of Glasgow failure

In 1878, one of Britain's largest banks, the City of Glasgow Bank, collapsed, leaving a huge deficit between its assets and liabilities. As this bank, similar to many other contemporary British banks, had unlimited liability, its failure was accompanied by the bankruptcy of the vast majority of its stockholders. It is generally believed that the collapse of this depository institution revealed the extent to which ownership in large joint-stock banks had been diffused to investors of very modest means. It is also believed that the failure resulted in bank shareholders dumping their shares unto the market. Our evidence, garnered from ownership records, trading data, and stock prices, offers no support for these widely held beliefs. © 2007 Elsevier Inc. All rights reserved.

An Unkind Cut: Circumcision, Death and the Impact of Irish Health Policy on Asylum Seekers

Healthcare and the wider social determinants of health are the keystone of a number of complex progressive social justice issues that evoke complex emotions. As the demography of Ireland rapidly changes, the practices and expectations of some asylum seekers presents new opportunities for the providers of health service provision and reform. This paper looks at some of the emotions evoked in health care issues and draws on observations and interviews from empirical fieldwork carried out for the Health Research Board. The research was conducted both in the Adelaide and Meath Hospital, incorporating the National Children’s Hospital, Tallaght and in a number of refugee reception centres in Ireland. At one level honouring faith choices within a healthcare setting is a societal acknowledgement made to people at their most vulnerable, that the potent and cathartic transformative rituals they value are significant in mediating and managing their emotions - at another level, it is a practical and a symbolic communication of a statutory commitment to inter-culturalism and community cohesion..

Factor markets in England before the Black Death

Modern English factor markets originated during the two centuries of active commercialization that preceded the Black Death. An active labour market was established by the late twelfth century. Evolution of a land market followed the legal reforms of the 1170s and 1180s, which created legally secure and defensible property rights in land. These rights stimulated growth of a capital market, since land became a security against which credit could be obtained. Nevertheless, none of these nascent factor markets functioned unconstrained and each became embedded in legal, tenurial, and institutional complexities and rigidities which it took later generations centuries to reform.

Targeting death receptors in bladder, prostate and renal cancer

PURPOSE: We describe key components of normal and aberrant death receptor pathways, the association of these abnormalities with tumorigenesis in bladder, prostate and renal cancer, and their potential application in novel therapeutic strategies targeted toward patients with cancer.

MATERIALS AND METHODS: A MEDLINE literature search of the key words death receptors, TRAIL (tumor necrosis factor related apoptosis inducing ligand), FAS, bladder, prostate, renal and cancer was done to obtain information for review. A brief overview of the TRAIL and FAS death receptor pathways, and their relationship to apoptosis is described. Mechanisms that lead to nonfunction of these pathways and how they may contribute to tumorigenesis are linked. Current efforts to target death receptor pathways as a therapeutic strategy are highlighted.

RESULTS: Activation of tumor cell expressing death receptors by cytotoxic immune cells is the main mechanism by which the immune system eliminates malignant cells. Death receptor triggering induces a caspase cascade, leading to tumor cell apoptosis. Receptor gene mutation or hypermethylation, decoy receptor or splice variant over expression, and downstream inhibitor interference are examples of the ways that normal pathway functioning is lost in cancers of the bladder and prostate. Targeting death receptors directly through synthetic ligand administration and blocking downstream inhibitor molecules with siRNA or antisense oligonucleotides represent novel therapeutic strategies under development.

CONCLUSIONS: Research into the death receptor pathways has demonstrated the key role that pathway aberrations have in the initiation and progression of malignancies of the bladder, prostate and kidney. This new understanding has resulted in exciting approaches to restore the functionality of these pathways as a novel therapeutic strategy.