Introduction 1. Woman's Place in Man's Life Cycle 2. Images of Relationship 3. Concepts of Self and Morality 4. Crisis and Transition 5. Women's Rights and Women's Judgment 6. Visions of Maturity References Index of Study Participants General Index

In a Different Voice. Psychological Theory and Women’s Development. Cambridge, MA (Harvard University Press) 1982.

Trust: The Social Virtues and the Creation of Prosperity

Evidence from clinical and experimental studies indicates that macrophages promote solid-tumour progression and metastasis. Macrophages are educated by the tumour microenvironment, so that they adopt a trophic role that facilitates angiogenesis, matrix breakdown and tumour-cell motility — all of which are elements of the metastatic process. During an inflammatory response, macrophages also produce many compounds — ranging from mutagenic oxygen and nitrogen radicals to angiogenic factors — that can contribute to cancer initiation and promotion. Macrophages therefore represent an important drug target for cancer prevention and cure.

Tumour-educated macrophages promote tumour progression and metastasis

1described the presence of cell-free nucleic acid (cfNA) in human blood for the first time. This attracted little attention in the scientific community and it was not until 1994 that the importance of cfNA was recognized as a result of the detection of mutated RAS gene fragments in the blood of cancer patients 2,3 (TIMELINE). In 1996, microsatellite alterations on cell-free DNA (cfDNA) were shown in cancer patients 4

/pdf/cell-free-nucleic-acids-as-biomarkers-in-cancer-patients-3cg84i0sga.pdf

Cell-free nucleic acids as biomarkers in cancer patients

DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. We apply a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in body samples of patients. Measurements of ctDNA can be used to reliably monitor tumor dynamics in subjects with cancer, especially those who are undergoing surgery or chemotherapy. This personalized genetic approach can be generally applied.

Circulating Mutant DNA to Assess Tumor Dynamics

Here we describe a patient with Crohn's disease who developed a severe infliximab infusion reaction (IIR), complicated 1 day later by severe swelling of the forearm and hand ipsilateral to the site of infliximab infusion. This proved to be extensive forearm deep venous thrombosis. The site of thrombosis and the chronological relationship with the IIR implicates a hypersensitivity to infliximab in the causation of the venous thrombosis in this case. With an increasing trend towards re-treating patients with known IIRs, clinicians should be aware of this potentially serious and previously unreported complication.

Extensive forearm deep venous thrombosis following a severe infliximab infusion reaction

Background and aims: The majority of patients with inflammatory bowel disease (IBD) have a normal life expectancy and therefore should not be weighted when applying for life assurance. There is scant literature on this topic. In this study our aim was to document and compare the incidence of difficulties in application for life and medical insurance in a population based cohort of IBD patients and matched population controls. Methods: A population based case control study of 1126 IBD patients and 1723 controls. Based on a detailed questionnaire, the frequency and type of difficulties encountered when applying for life and medical insurance in matched IBD and control populations were appraised. Results: In comparison with controls, IBD patients had an 87-fold increased risk of encountering difficulties when applying for life assurance (odds ratio (OR) 87 (95% confidence interval (CI) 31–246)), with a heavily weighted premium being the most common problem. Patients of high educational status, with continuous disease activity, and who smoked had the highest odds of encountering such problems. Medical insurance difficulties were fivefold more common in IBD patients compared with controls (OR 5.4 (95% CI 2.3–13)) although no specific disease or patient characteristics were identified as associated with such difficulties. Conclusions: This is the first detailed case control study that has investigated insurance difficulties among IBD patients. Acquiring life and medical insurance constituted a major problem for IBD patients in this study. These results are likely to be more widely representative given that most insurance companies use international guidelines for risk assessment. In view of the recent advances in therapy and promising survival data on IBD patients, evidence based guidelines for risk assessment of IBD patients by insurance companies should be drawn up to prevent possible discriminatory practices.

https://gut.bmj.com/content/gutjnl/52/3/358.full.pdf

Insurance problems among inflammatory bowel disease patients: results of a Dutch population based study

IntroductionThe role of antitumour necrosis factor agents, in particular infliximab in ulcerative colitis (UC) has been well established. More recently adalimumab, a fully humanized antitumour necrosis factor α monoclonal antibody, was licensed for refractory moderately active UC in 2012. Available

Long-term assessment of clinical response to adalimumab therapy in refractory ulcerative colitis.

Research and development of classroom based resources for bioethics education in New Zealand

Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohn’s disease (CD) although as yet the exact mechanisms have not been fully elucidated. 
To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model. Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients’ and pre- and post-treatment CD patients’ sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed. 
There was a significant increase in bone formation markers osteocalcin (P < 0.05) and procollagen type 1 N-terminal propeptide (P < 0.01) at 1 and 3 months post-treatment. Moreover, there was a sustained but not significant fall in serum CTx, a bone resorption marker. No significant change was seen over time with other parameters measured. Serum from CD patients pre-treated with adalimumab showed increased osteoblast viability compared with that of post-treated patients at 6 months (P = 0.002) and controls. However, post-adalimumab treatment sera at 6 months appeared to increase osteoblast differentiation (P = 0.001), which is likely to be important in new bone formation. This first study evaluating the role of adalimumab as a possible bone protector in Crohn’s disease patients has shown that similar to infliximab, adalimumab has complex and potentially beneficial effects on bone metabolism.

Barbara Ryan

Papers

Extensive forearm deep venous thrombosis following a severe infliximab infusion reaction

Insurance problems among inflammatory bowel disease patients: results of a Dutch population based study

Long-term assessment of clinical response to adalimumab therapy in refractory ulcerative colitis.

Research and development of classroom based resources for bioethics education in New Zealand

Adalimumab Therapy Has a Beneficial Effect on Bone Metabolism in Patients with Crohn's Disease.