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Le suicide est un enjeu majeur de santé publique au Canada. Si les facteurs individuels et démographiques influent sur le taux de suicide, la qualité des services de santé a également un impact. Dans un système public de soins comme celui du Canada ou celui du Royaume-Uni, la qualité des soins se manifeste à trois niveaux : individuel, programmatique et systémique. L'examen des suicides sert à évaluer les services de santé quant au décès par suicide et, au niveau agrégé, à évaluer ces services à l’échelle des programmes et du système. Les grandes bases de données médico-administratives constituent une autre source de données utile à la prise de décisions sur l’ensemble de la population à l’échelle systémique, programmatique et individuelle et portant sur les services en santé mentale susceptibles d'avoir une influence sur le risque de suicide. Cet article décrit un projet mené à l’Institut national de santé publique du Québec (INSPQ) utilisant le Système intégré de surveillance des maladies chroniques du Québec (SISMACQ), en collaboration avec des collègues du pays de Galles (Royaume-Uni) et de l’Institut norvégien de santé publique. Cette étude décrit l’élaboration d’indicateurs de la qualité des soins à ces trois niveaux et les stratégies connexes d’analyse statistique. Nous proposons 13 indicateurs de soins de santé pouvant être créés à partir d’un système de surveillance des maladies chroniques : déterminant systémique, déterminants démographiques, soins primaires, soins spécialisés, équilibre entre les secteurs de soins, consultation à l’urgence et budgets en santé mentale et toxicomanie.

Responsibility for suicide prevention falls to the Government of Canada and Health Canada. The issue of suicide affects Canadians of all ages and in all regions of the country, hence the need for a pan-Canadian strategy aimed at reducing suicide deaths and reaching all Canadians. The availability and accessibility of mental health services constitute important resources for suicide prevention and a target for interventions that can be made to rapidly reduce the suicide rate. Such a strategy to improve services should include quality surveillance and quality control programs, such as suicide audits and the use of linked government administrative databases. Population-based strategies to prevent and treat depression must also be established and should be based on the Nuremberg model. In particular, development of equitable access to psychotherapy and mental health literacy programs should be priority goals.

Three theories have been proposed to explain the relationship between suicide and economic fluctuations, including the Durkheim (nonlinear), Ginsberg (procyclical), and Henry and Short (countercyclical) theories. This study tested the effect of economic fluctuations, measured by unemployment rate, on suicide rates in Canada from 1926 to 2008. Autoregressive integrated moving average time-series models were used. The results showed a significant relationship between suicide and economic fluctuation; this association was positive during the contraction period (1926-1950) and negative in the period of economic expansion (1951-1973). Males and females showed differential effects in the period of moderate unemployment (1974-2008). In addition, the suicide rate of mid-adults (45-64) was most impacted by economic fluctuations. Our study tends to support Durkheim's theory and suggests the need for public health responses in times of economic contraction and expansion.

Suicide is a major public health issue in Canada. The quality of health care services, in addition to other individual and population factors, has been shown to affect suicide rates. In publicly managed care systems, such as systems in Canada and the United Kingdom, the quality of health care is manifested at the individual, program and system levels. Suicide audits are used to assess health care services in relation to the deaths by suicide at individual level and when aggregated at the program and system levels. Large health administrative databases comprise another data source used to inform population-based decisions at the system, program and individual levels regarding mental health services that may affect the risk of suicide. This status report paper describes a project we are conducting at the Institut national de santé publique du Québec (INSPQ) with the Quebec Integrated Chronic Disease Surveillance System (QICDSS) in collaboration with colleagues from Wales (United Kingdom) and the Norwegian Institute of Public Health. This study describes the development of quality of care indicators at three levels and the corresponding statistical analysis strategies designed. We propose 13 quality of care indicators, including system-level and several population-level determinants, primary care treatment, specialist care, the balance between care sectors, emergency room utilization, and mental health and addiction budgets, that may be drawn from a chronic disease surveillance system.Le suicide est un enjeu majeur de santé publique au Canada. Si les facteurs individuels et démographiques influent sur le taux de suicide, la qualité des services de santé a également un impact. Dans un système public de soins comme celui du Canada ou celui du Royaume-Uni, la qualité des soins se manifeste à trois niveaux : individuel, programmatique et systémique. L'examen des suicides sert à évaluer les services de santé quant au décès par suicide et, au niveau agrégé, à évaluer ces services à l’échelle des programmes et du système. Les grandes bases de données médico-administratives constituent une autre source de données utile à la prise de décisions sur l’ensemble de la population à l’échelle systémique, programmatique et individuelle et portant sur les services en santé mentale susceptibles d'avoir une influence sur le risque de suicide. Cet article décrit un projet mené à l’Institut national de santé publique du Québec (INSPQ) utilisant le Système intégré de surveillance des maladies chroniques du Québec (SISMACQ), en collaboration avec des collègues du pays de Galles (Royaume-Uni) et de l’Institut norvégien de santé publique. Cette étude décrit l’élaboration d’indicateurs de la qualité des soins à ces trois niveaux et les stratégies connexes d’analyse statistique. Nous proposons 13 indicateurs de soins de santé pouvant être créés à partir d’un système de surveillance des maladies chroniques : déterminant systémique, déterminants démographiques, soins primaires, soins spécialisés, équilibre entre les secteurs de soins, consultation à l’urgence et budgets en santé mentale et toxicomanie.

Suicide is a major public health issue in Canada. The quality of health care services, in addition to other individual and population factors, has been shown to affect suicide rates. In publicly managed care systems, such as systems in Canada and the United Kingdom, the quality of health care is manifested at the individual, program and system levels. Suicide audits are used to assess health care services in relation to the deaths by suicide at individual level and when aggregated at the program and system levels. Large health administrative databases comprise another data source used to inform population- based decisions at the system, program and individual levels regarding mental health services that may affect the risk of suicide. This status report paper describes a project we are conducting at the Institut national de santé publique du Québec (INSPQ) with the Quebec Integrated Chronic Disease Surveillance System (QICDSS) in collaboration with colleagues from Wales (United Kingdom) and the Norwegian Institute of Public Health. This study describes the development of quality of care indicators at three levels and the corresponding statistical analysis strategies designed. We propose 13 quality of care indicators, including system-level and several population-level determinants, primary care treatment, specialist care, the balance between care sectors, emergency room utilization, and mental health and addiction budgets, that may be drawn from a chronic disease surveillance system.

A method has been developed to purify rat liver nuclei; the isolated nuclei keep both nuclear membranes and retain more than 90% of the cell apurinic/apyrimidinic (AP) endodeoxyribonuclease activity. The nuclear enzyme is located mostly in chromatin non-histones; there is also an important amount of activity in the nuclear sap and some in the nuclear membranes. The cytoplasmic AP endodeoxyribonuclease activity is shared between mitochondria, cytosol and membranes. Different cell compartments appear to contain different AP endodeoxyribonuclease species: the membrane enzyme is activated by Triton whereas the other enzymes are rather inhibited; the nuclear sap enzyme has a higher molecular weight and a higher thermal resistance than the chromatin enzyme. A hypothesis is formulated according to which: (1) the chromatin enzyme is the only species important for nuclear DNA repair; (2) the species present in the other cell compartments might be precursors of the chromatin AP endodeoxyribonuclease.

Suicide rates raise with age has remained consistent for more than 150 years but over the last 50 years major changes occurred. We examined Age-Period-Cohort (APC) effects on suicide mortality rate by gender in Canada and in Quebec from 1926 to 2008. Durkheim theoretical framework is used to interpret our findings. Descriptive analysis and APC models relating to the Intrinsic Estimator (IE) were used to assess these effects. IE model shows suicide net age effect for men in Canada and Quebec as death rate increased until 25 years old before reaching a plateau. For women it’s an inverted "U" shape peaking at mid-adulthood. While period effect differs, a net cohort effect is found for men born in 1941, and women in 1981 until most recent cohorts.

The role of liposomes in antigen presentation and in induction of humoral and cell-mediated immune responses has been investigated by anchoring viral envelope glycoproteins into the phospholipidic bilayer of preformed liposomes to produce Immunosomes. Using purified glycoproteins of three different enveloped viruses, it was found that in mice immunosomes induced high titres of neutralizing antibodies, whereas equal amounts of the purified glycoproteins alone failed to induce or induced much lower neutralizing antibodies. Similarly, immunosomes induced in vaccinated animals antigenspecific interleukin-2 production upon in vitro restimulation with the same antigen, whereas no secondary response was observed in animals vaccinated with equal amounts of the free antigen. Finally, influenza and rabies immunosomes were shown to be efficient in protecting animals from a challenge with the corresponding virulent strain.

Rabies immunosomes (glycoprotein anchored on pre-formed liposomes) have been prepared in order to study their structural, biological and immunological properties. The glycoprotein molecules appear to have the same orientation on the immunosome as on the viral particle: (1) electron microscopy analysis shows particles of 40 to 70 nm with spikes protruding outward, (2) one particular epitope shows the same accessibility to a neutralizing monoclonal antibody as on the viral particle. When injected into animals, rabies immunosomes are cleared from the organism by a process different from that for the liposomes used to anchor the glycoprotein: a higher rate of transition through the spleen is observed with immunosomes than with purified glycoprotein or liposomes. Immunosomes induce high levels of neutralizing antibodies and protect animals against challenge with virulent strains. This protective activity is not altered after several months of storage at 4 degrees C. Furthermore, rabies immunosomes were shown to be efficient in post-exposure treatment of laboratory animals that had been experimentally infected with a lethal dose of a rabies wild strain.

Neutralizing monoclonal antibodies were produced against a reference vaccine or a reference wild strain of poliovirus type 1, 2, and 3. After 26 fusions, 55 monoclonal antibodies were obtained with serotype 1 as the immunizing antigen, 180 with serotype 2, and 115 with serotype 3. The neutralizing activity of these monoclonal antibodies was tested first with the two reference strains and then if reactive, against a panel of 10 well-characterized strains of each serotype, 5 vaccinelike (VL) and 5 non vaccinelike (NVL). All monoclonal antibodies were type specific without reactivity with any of the heterologous strains. There was a wide range of reactivity within the strains of each serotype. Several monoclonal antibodies to serotype 1 reacted with all type 1 strains, while several neutralized strongly all VL strains and weakly one or more of the NVL strains. Most of the 180 monoclonal antibodies to serotype 2 neutralized to various degrees all strains of this serotype and about half reacted very strongly with all homologous strains whether VL or NVL. None could differentiate all VL and NVL homologous strains. Of the 115 monoclonal antibodies to serotype 3, several monoclonal antibodies neutralize to various levels all homologous strains and some can differentiate VL and NVL strains.Key words: poliovirus, monoclonal antibody, neutralization, serodifferentiation.

BALB/c mice were primed by receiving a unique intraperitoneal injection of rabies virus antigens presented as complete inactivated virus (P.V. strain) or as purified glycoproteins either in the aggregated form or in physical combination with liposomes (i.e., in the form of “immunosomes”). The splenocytes of these mice were restimulated, 6–15 days after priming, in culture with rabies virus antigens, and antigen-specific IL-2 production was measured. It was found that rabies antigens presented as immunosomes were as active as the inactivated virus, whereas equivalent amounts of purified glycoproteins were inactive. The optimal amounts of rabies immunosomes used for priming was found to be 0.5 to 0.05 μg per mouse.

Two nucleases active on alkylated-depurinated DNA have been extracted from rat liver chromatin with 1 M KCl. The major enzyme was purified to near homogeneity; it has a molecular weight of 12 500 (although some dimerization might occur), needs Mg2+ or Mn2+ for activity. The endonuclease activity is specific for apurinic/apyrimidinic sites in DNA; the enzyme has no associated exonuclease activity.

When injected as an immunosome presentation (molecules anchored to preformed liposome), rabies glycoprotein (GP) is capable of protecting animals against rabies either before or after viral infection. The presentation of the GP molecules in the correct form seems to be essential for the induction of antirabies protection. This condition must be taken in account in the making-up of a rabies subunit vaccine. In order to study the relationship between the immune responses induced by the rabies GP and its protective activity, different presentations of the GP were prepared. Purified glycoprotein molecules were associated under different physical forms: liposome-anchored, self-aggregated (rosettes) and associated with the viral lipids (virosomes). These presentations appeared different on electron microscopy. They also exhibited differences in the expression of an immunodominant epitope and in their protective activity. The non-specific immune response, as appraised by interferon production and natural cytotoxicity, was induced at a high level only by the purified viral particles. Specific immune responses (namely virus neutralizing antibody and interleukin-2 production) was induced at high levels only by the viral particle and by the liposome-anchored glycoprotein. A parallelism has previously been established between protection by glycoprotein preparations and interleukin-2 production in primed mice splenocytes. This suggests that the measure of interleukin-2 production in vitro could be used to evaluate the capability of a rabies antigen to induce a T-cell response and to confer protection.

1) A DNA damage is not a mutation; the damage must be processed by several cycles of DNA replication before it eventually becomes a mutation; 2) Most DNA damages, which are potentially mutagenic and carcinogenic, are repaired; 3) A competition between repair and DNA replication fixes the mutation rate. An established mutation can no longer be repaired; 4) DNA repair is the first line of defense against cancers due to physical and chemical mutagens. Repair deficiencies are associated with a high incidence of cancers; 5) In eucaryotic cells, repair enzymes have been located in chromatin non-histone proteins; 6) Native chromatin exhibits little activity on an added damaged DNA. The non-histone proteins must be separated to demonstrate the full activity of the enzymes on such a substrate; 7) DNA repair in vivo might depend not only on repair enzymes but also on other chromatin proteins necessary for the correct orientation of the enzymes to work on chromatin DNA; 8) We have observed a release of O6-ethylguanine, a modified base thought to be mutagenic and carcinogenic, from isolated nuclei treated with ethylnitrosourea. This result suggests that the first enzyme involved in the repair of this carcinogenic damage might belong to the class of DNA glycosylases.

1. ABSTRACT The current influenza virus vaccines made of inactivated particles often induce undesirable local and general pyrogenic reactions particularly among youngsters. We have made a selective extraction of membrane glycoproteins and constructed an immunosome which is exclusively made of hemagglutinin and neuraminidase attached onto the membrane of a preformed liposome. The phospholipids were solubilized with the detergent β-D-octylglucoside and the liposomes were formed by the injection method. The hemagglutinins were extracted from purified influenza viruses with Triton N-101. The solubilized glycoproteins were purified by centrifugation through a discontinuous sucrose gradient; the non-dialysable Triton was exchanged during the centrifugation for β-D-octylglucoside that was incorporated into the gradient. When the hemagglutinin subunits, free of detergent, were mixed with preformed liposomes, the incorporation on the surface membrane was extremely low. This difficulty could be overcome by mixing a protein-detergent complex with preformed liposomes, the membranes of which had been “fluidified” in the presence of minute amounts of detergent. A decreasing detergent gradient dialysis allowed the exchange of the proteins from detergent to the phospholipid bilayer. This technique recreates a structure that is almost indistinguishable from the virus particle. This immunosome is highly immunogenic and possesses an hemagglutinating activity much greater than the viral subunits.

Vaccination with either whole inactivated rabies virus or immunosome (rabies glycoprotein anchored on liposomes) induces a high level of interleukin 2 (IL 2) production after in vitro specific stimulation of splenocytes from primed mice (9). On the contrary, infection with a live rabies virus does not specifically induce the production of IL 2: splenocytes from ill mice previously infected with wild rabies virus cannot be specifically stimulated by rabies antigens, whereas they can be non-specifically stimulated by a mitogen (Concanavalin A (Con A]. When injected in mice, exogenous IL 2 (purified rat IL 2 or human recombinant IL 2) exhibits an adjuvant effect on rabies virus vaccine or subunit vaccine tested in a pre-exposure potency test (NIH test). When injected in hamsters, according to a post-exposure potency test (infection with a wild rabies virus followed by vaccination), IL 2 has no adjuvant effect on the rabies vaccine. Nevertheless, when injected alone, IL 2 protects thirty to fifty percent of the infected animals treated (1 hour, 3 and 7 days post-infection) with 10 international units of human recombinant IL 2.

Antigen-specific IL-2 production was assessed, using splenocytes from rabies immune mice incubated for 24 h with rabies virus antigen. The antigenic material used for in vivo priming was either purified glycoprotein from rabies virus, or the inactivated virus. The time between priming, harvesting and restimulation of the splenocytes was 7 days. It was found that when antigenically inert liposomes were injected, together with antigenic material, to the prospective splenocyte donor mice, IL-2 production was enhanced. This augmentation was observed particularly when priming was performed with the inactivated rabies virus.