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.     

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.     

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.     

Characterization of the sleep-wake patterns in mice lacking fatty acid amide hydrolase

STUDY OBJECTIVES: Oleamide and anandamide are fatty acid amides implicated in the regulatory mechanisms of sleep processes. However, due to their prompt catabolism by fatty acid amide hydrolase (FAAH), their pharmacologic and behavioral effects, in vivo, disappear rapidly. To determine if, in the absence of FAAH, the hypnogenic fatty acid amides induce an increase of sleep, we characterized the sleep-wake patters in FAAH-knockout mice [FAAH (-/-)] before and after sleep deprivation. DESIGN: FAAH (-/-), FAAH (+/-), and FAAH (+/+) mice were implanted chronically for sleep, body temperature (Tb), and locomotor activity (LMA) recordings. Sleep-wake states were recorded during a 24-hour baseline session followed by 8 hours of sleep deprivation. Recovery recordings were done during the 16 hours following sleep deprivation. Total amount of wake, slow-wave sleep, and rapid eye movement sleep were calculated and compared between genotypes. The electroencephalographic spectral analysis was performed by fast Fourier transform analysis. Telemetry recordings of Tb and LMA were carried out continuously during 4 days under baseline conditions. SETTING: N/A. PATIENTS OR PARTICIPANTS: FAAH (-/-) mice and their heterozygote (+/-) and control (+/+) littermates were used. INTERVENTIONS: Sleep deprivation. MEASUREMENTS AND RESULTS: FAAH (-/-) mice possess higher values of slow-wave sleep and more intense episodes of slow-wave sleep than do control littermates under baseline conditions that are not related to differences in Tb and LMA. A rebound of slow-wave sleep and rapid eye movement sleep as well an increase in the levels of slow-wave activity were observed after sleep deprivation in all genotypes. CONCLUSION: These findings support the role of fatty acid amides as possible modulators of sleep and indicate that the homeostatic mechanisms of sleep in FAAH (-/-) mice are not disrupted.     

Post-marketing surveillance of enalapril: experience in 11 710 hypertensive patients in general practice

Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.7% of patients, though most of these were not thought to be related to the treatment. The incidence rates of death (0.09%), stroke (0.11%) and myocardial infarction (0.15%) were compatible with rates predicted from age, sex and blood pressure considerations. Other events reported were hypotension (0.3%), angioneurotic oedema (0.03%), rash (0.5%), taste disturbance (0.2%) and cough (1.0%). The degree of blood pressure reduction attained was similar to that previously reported from pre-marketing development studies, as was the overall nature and frequency of both serious and non-serious adverse events. The most frequently reported event during enalapril therapy was of an improvement in well-being (19.8%).     

Methoxsalen stimulates electrogenic Cl- secretion in the mouse jejunum

We used the short-circuit current (I(sc)) and patch-clamp techniques to investigate the effects of methoxsalen (MTX) on the electrogenic Cl- secretion of the mouse jejunum. MTX stimulated a sustained increase in Isc that was dose dependent. Bumetanide inhibited MTX-stimulated Isc in a dose-dependent manner consistent with activation of Cl- secretion. MTX failed to stimulate I(sc) following maximal activation of the cAMP pathway by forskolin, but did increase Isc after a submaximal dose of forskolin. Glibenclamide, a blocker of the cystic fibrosis transmembrane conductance regulator (CFTR), reduced the MTX-stimulated increase of Isc by 59 +/- 6%. The cAMP-dependent K+ channel blocker 293B did not alter the MTX-activated I(sc); however, clotrimazole, an intermediate Ca2(+)-activated K+ channel (IK(Ca)) blocker, reduced the MTX-stimulated I(sc). MTX did not alter Na(+)-glucose cotransport across the mouse jejunum. In cell-attached membrane patches, MTX increased the open probability of the basolateral IK(Ca) channel of isolated crypts. These data suggest that the CFTR and IK(Ca) channels participate in the MTX-activated, sustained Cl- secretory response of the mouse jejunum.