Researching with young people on health and environment: the politics of self-esteem and stress

This paper describes a research project with young people froma group called the Bellarine Youth Network (BYN). The projectinvolved the identification of the perceptions of health andenvironmental issues held by these young people. A foundationof the project was that perceptions of health and environmentwere socially constructed, and reflected vested interests andpolitical agendas. Traditional positivist research projects(designs) which attempted to generalize, marginalize and categorizeyoung people were seen as inappropriate for this study. Themost pressing environmental health concern for the members ofthe BYN was stress caused by school work. Attempts by communityhealth workers, psychologists and consultants to minimize thestress felt by young people only served to individualize theproblem. These attempts included diary keeping, time managementskills, and the maintenance of a balance between work and leisureactivities. These individualistic strategies to reduce stresswere also based on the often perceived centrality of the conceptof self-esteem. There was rarely any understanding of the complexlives of young people and the range of identities held by them.Instead of simplistic and naive projects focusing on self-esteem,future research with young people needs to be more sympatheticto the relationships between behaviour, context (or settingor environment) and meaning, and also needs to involve a recognitionof the importance to young people of the varied social environmentswithin which they find themselves.     

Nipple centralization for the correction of breast deformity from segmental mastectomy

A breast deformed by lateral tissue deficiency and severe lateral displacement of the nipple, caused by the treatment of an early breast cancer with segmental mastectomy and radiotherapy, was corrected by a modification of techniques used commonly for mastopexy. The nipple and areola were moved medially on a central pedicle to create the illusion that the missing lateral tissues had been restored. Simultaneously, the opposite breast was reduced to improve symmetry. The result was a normalization of breast appearance without the need for distant tissue. It is possible that modifications of this approach could be used to treat similar deformities in other quadrants of the breast as well.     

Cognitive-behavioral treatment of late-life generalized anxiety disorder

This study addressed the efficacy of cognitive-behavioral therapy (CBT), relative to minimal contact control (MCC), in a sample of 85 older adults (age 60 years and over) with generalized anxiety disorder (GAD). All participants completed measures of primary outcome (worry and anxiety), coexistent symptoms (depressive symptoms and specific fears), and quality of life. Results of both completer and intent-to-treat analyses revealed significant improvement in worry, anxiety, depression, and quality of life following CBT relative to MCC. Forty-five percent of patients in CBT were classified as responders, relative to 8% in MCC. Most gains for patients in CBT were maintained or enhanced over 1-year follow-up. However, posttreatment scores for patients in CBT failed to indicate return to normative functioning.     

Single step enrichment of blood dendritic cells by positive immunoselection

Dendritic cells (DC) for cancer immunotherapy protocols are generated most commonly by in vitro differentiation of monocytes with exogenous cytokines (Mo-DC). However, Mo-DC differ in their molecular phenotype and function from blood DC (BDC). Clinical isolation of BDC has been limited to the use of density gradients, which result in low yields of variable purity. We have developed a DC enrichment platform, which uses the CMRF-44 (IgM) or CMRF-56 (IgG) monoclonal antibodies (mAb) to select BDC that express these antigens after a short overnight incubation. After culture of peripheral blood mononuclear cells (PBMC) in autologous/AB serum, biotinylated CMRF-44 was used to select DC in a single step immuno-magnetic bead procedure; this produced populations containing up to 99% CMRF-44(+) cells, including up to 67% CMRF-44(+) CD14(-) CD19(-) DC, from an initial starting population of approximately 0.5%. We observed consistent differences in the purities obtained from individual donors with a mean of 54% CMRF-44(+) cells (range 19-99%). Similar results were obtained using biotinylated CMRF-56 mAb, an antibody identifying a comparable population in cultured PBMC. We recovered an average of 54% and 66% of the available BDC in separations performed with the CMRF-44 and CMRF-56 mAb, respectively. The reproducibility of the procedure and the ability to perform it in a closed sterile system makes it suitable for clinical use. Larger scale preparations starting from apheresis derived PBMC will produce sufficient BDC for immunotherapy protocols. The purified BDC elicited strong allogeneic mixed leukocyte reactions and HLA classes II- and I-restricted antigen-specific primary immune responses.     

An AscI boundary library for the studies of genetic and epigenetic alterations in CpG islands

Knudson's two-hit hypothesis postulates that genetic alterations in both alleles are required for the inactivation of tumor-suppressor genes. Genetic alterations include small or large deletions and mutations. Over the past years, it has become clear that epigenetic alterations such as DNA methylation are additional mechanisms for gene silencing. Restriction Landmark Genomic Scanning (RLGS) is a two-dimensional gel electrophoresis that assesses the methylation status of thousands of CpG islands. RLGS has been applied successfully to scan cancer genomes for aberrant DNA methylation patterns. So far, the majority of this work was done using NotI as the restriction landmark site. Here, we describe the development of RLGS using AscI as the restriction landmark site for genome-wide scans of cancer genomes. The availability of AscI as a restriction landmark for RLGS allows for scanning almost twice as many CpG islands in the human genome compared with using NotI only. We describe the development of an AscI-EcoRV boundary library that supports the cloning of novel methylated genes. Feasibility of this system is shown in three tumor types, medulloblastomas, lung cancers, and head and neck cancers. We report the cloning of 178 AscI RLGS fragments via two methods by use of this library.     

Multiple mutations in mouse Chd7 provide models for CHARGE syndrome

Mouse ENU mutagenesis programmes have yielded a series of independent mutations on proximal chromosome 4 leading to dominant head-bobbing and circling behaviour due to truncations of the lateral semicircular canal of the inner ear. Here, we report the identification of mutations in the Chd7 gene in nine of these mutant alleles including six nonsense and three splice site mutations. The human CHD7 gene is known to be involved in CHARGE syndrome, which also shows inner ear malformations and a variety of other features with varying penetrance and appears to be due to frequent de novo mutation. We found widespread expression of Chd7 in early development of the mouse in organs affected in CHARGE syndrome including eye, olfactory epithelium, inner ear and vascular system. Closer inspection of heterozygous mutant mice revealed a range of defects with reduced penetrance, such as cleft palate, choanal atresia, septal defects of the heart, haemorrhages, prenatal death, vulva and clitoral defects and keratoconjunctivitis sicca. Many of these defects mimic the features of CHARGE syndrome. There were no obvious features of the gene that might make it more mutable than other genes. We conclude that the large number of mouse mutants and human de novo mutations may be due to the combination of the Chd7 gene being a large target and the fact that many heterozygous carriers of the mutations are viable individuals with a readily detectable phenotype.     

Thrombus of the ascending aorta: a rare cause of myocardial infarction.

We present two cases of a thrombus in the ascending aorta causing an acute myocardial infarction (AMI) and review the 10 other cases previously reported in the literature. This life-threatening condition appears to be more common in female smokers in their fifth decade. Suspicion should be raised in individuals at low risk for atherosclerotic disease with coronary angiographic findings not in keeping with the clinical presentation. The diagnosis may be obtained by transesophageal echocardiography, and we generally recommend surgical thrombectomy.