Substitute Consent for Research Involving the Elderly: A Comparison Between Quebec and France

The authors first describe the rules enacted in Quebec and France to protect adults with decisional impairment who may be approached by investigators to participate in research protocols. They then present two consecutive postal surveys conducted among Quebec and French researchers in aging and designed to (1) assess their knowledge of the legal provisions implemented to protect decisionally incapable adults, (2) elicit their opinions regarding the person best suited to provide substitute consent for research participation, and (3) document their conduct related to obtaining consent for prospective subjects with impaired decisional capacity. Knowledge of the legislation governing substitute consent was poor, even more so among French than Quebec researchers (p < 0.001). In both samples, the majority of respondents felt that the substitute decision-maker does not have to be legally appointed when the study poses little risk to the participant. Practice data revealed a certain discrepancy between the conduct of researchers in aging and the legal provisions regarding consent for research purposes that prevail in their jurisdictions. These findings underscore the need to better educate clinical investigators about existing measures to protect prospective subjects who lack decisional capacity. They also provide some support for allowing close relatives to consent to research participation on behalf of older adults who are unable to consent by themselves and have not been appointed a legal representative.     

Cranial manifestations of Recklinghausen's disease. A case report

A typical case of Recklinghausen's disease is presented, and the various cephalic manifestations and prognosis discussed. A close relation exists between neurofibromatosis and neural crest lesions.     

NOS 1 is required for allergen-induced expression of NOS 2 in mice

BACKGROUND: Although increased nitric oxide (NO) production in asthma is mediated largely by upregulation of the inducible form of nitric oxide synthase (iNOS, or NOS 2), some studies have suggested an important role for the usually constitutive neural NOS isoform (nNOS, or NOS 1). AIM: To investigate how NOS 1 may influence allergic inflammation, we used NOS 1 knockout mice and their wild-type (WT) controls. METHODS: Mice were sensitized and challenged with ovalbumin (OVA) using a protocol known to upregulate NOS 2 in the airways. RESULTS: In addition to expected increases in NOS 2 activity, OVA challenge led to increases in calcium-dependent NOS activity, which was accounted for by increased expression of NOS 1 at both mRNA (n = 5, p < 0.001) and protein levels (n = 5, p < 0.01). In NOS-1-deficient mice, OVA challenge induced less eosinophilia (n = 7, p < 0.05) and much less NO production (n = 10, p < 0.01) than in WT controls, reflecting not only the expected absence of NOS 1, but also lack of upregulation of NOS 2. This interaction appeared to be stimulus specific as NOS-1-deficient mice did upregulate NOS 2 following exposure to lipopolysaccharide (n = 5, p < 0.001). CONCLUSIONS: These findings underscore the importance of NOS 1 in allergic airway inflammation and suggest a mechanism by which NOS 1 may influence overall NO production in the airways.     

Reparative giant cell granuloma: long-term follow up. Apropos of a case

The authors report a case of an 8 year old boy, who was operated for a giant cell reparative granuloma of the mandibular symphysis. During follow-up, two dentigerous cysts were surgically removed, in the same area. No recurrence of the GCGR was noted 5 years after removal.     

Eosinophil peroxidase mediates protein nitration in allergic airway inflammation in mice.

The eosinophilic inflammatory response in asthma is associated with protein nitration, detected as immunostaining for 3-nitrotyrosine (3NT). As the presence of 3NT is strongly correlated with upregulation of the inducible form of nitric oxide synthase (NOS II), it has been hypothesized that 3NT formation results from the action of peroxynitrite (ONOO-), a highly reactive NO derivative produced from the reaction of molecular NO and O2-. However, recent observations have suggested that the action of peroxidases, including eosinophil peroxidase (EPO), may be responsible for protein nitration. In this study, we used murine models of allergic asthma to address the relative contribution of EPO and NOS II to protein nitration. We studied EPO-deficient New Zealand White (NZW) mice, which were sensitized and challenged intranasally with ovalbumin (OVA). Despite comparable levels of eosinophilia, NO, and superoxide production, NZW mice exhibited markedly decreased 3NT staining around the airways after OVA challenge when compared with two other strains (A/J and C57BL/6J). Immunocytochemical analysis of bronchoalveolar lavage (BAL) cells and lung sections suggested that 3NT staining was largely confined to eosinophils. This was confirmed by Western Blot analysis of proteins from different subsets of BAL cells that demonstrated a marked decrease in 3NT formation in eosinophils from NZW mice. These results contrast with those obtained in OVA-sensitized and -challenged NOS II deficient mice, which despite decreased NO production, exhibited similar 3NT staining in the airways after OVA challenge as in wild-type control mice. In this model, protein nitration was thus not a function of NO production by NOS II. We conclude that in the mouse, 3NT formation after specific allergen challenge is dependent on EPO activity, particularly in eosinophils themselves. In contrast, 3NT formation is not driven by upregulation of NOS II expression in this model and does not appear to depend on increases in the level of NO production.