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Biomedical subjects

R Bernier

Publications and source records attributed to R Bernier.

At least 19 recordsLinked to original sources
PubMed2000

Assessing immunization coverage in private practice.

To achieve national health objectives of eliminating most childhood vaccine-preventable diseases by the year 2010, all health care providers will have to improve the immunization rates of their patients. Currently, immunization rates of children 19 to 35 months of age are less than national objectives, suggesting a need for optimized immunization services. A key strategy for improving age-appropriate immunization coverage by health care providers is the assessment of immunization coverage. Because most (62%), immunization services in the United States are delivered in the private sector, a concerted effort in private practice is critical to improving immunization rates. Assessment of immunization coverage of patients enrolled in private practice serves 1) to measure the overall performance of the practice in providing the standard of care, 2) to identify strategies for improving coverage, and 3) to document the quality of health services delivered (report card). Assessment of immunization coverage has been demonstrated in several practice settings to be highly effective in improving immunization rates. All types of physicians should benefit from assessing immunization coverage of their patients. Simple assessment tools are available at no cost to the public and can be obtained by contacting the Centers for Disease Control and Prevention. These tools include a manual self-assessment or a computerized software package (CASA) to fit the needs of the practice.

Centers for Disease Control and Prevention, U.S.↗
PubMed1999

An autosomal genomic screen for autism. Collaborative linkage study of autism.

Autism is a severe neurodevelopmental disorder defined by social and communication deficits and ritualistic-repetitive behaviors that are detectable in early childhood. The etiology of idiopathic autism is strongly genetic, and oligogenic transmission is likely. The first stage of a two-stage genomic screen for autism was carried out by the Collaborative Linkage Study of Autism on individuals affected with autism from 75 families ascertained through an affected sib-pair. The strongest multipoint results were for regions on chromosomes 13 and 7. The highest maximum multipoint heterogeneity LOD (MMLS/het) score is 3.0 at D13S800 (approximately 55 cM from the telomere) under the recessive model, with an estimated 35% of families linked to this locus. The next highest peak is an MMLS/het score of 2.3 at 19 cM, between D13S217 and D13S1229. Our third highest MMLS/het score of 2.2 is on chromosome 7 and is consistent with the International Molecular Genetic Study of Autism Consortium report of a possible susceptibility locus somewhere within 7q31-33. These regions and others will be followed up in the second stage of our study by typing additional markers in both the original and a second set of identically ascertained autism families, which are currently being collected. By comparing results across a number of studies, we expect to be able to narrow our search for autism susceptibility genes to a small number of genomic regions. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:609-615, 1999.

Adolescent↗
PubMed1999

Antiplatelet and lipid-lowering therapies for the secondary prevention of cardiovascular disease: are we doing enough?

OBJECTIVE: To evaluate whether current recommendations with respect to the treatment of dyslipidemias and the use of antiplatelet agents are being applied in the secondary prevention of cardiovascular disease in primary care settings. DESIGN: Descriptive study based on data from the FAMUS (FAmily Medicine, Université de Sherbrooke) primary care register. SETTING AND PARTICIPANTS: Two-hundred and thirty-three physicians participating in the FAMUS project contributed information from nonpregnant patients over 20 years of age consulting for a periodic health examination between 1992 and 1996. INTERVENTIONS: Data from patients in secondary prevention (those with or having had angina, a previous myocardial infarction, bypass surgery, coronary angioplasty or peripheral vascular disease) were extracted and analyzed. MAIN RESULTS: Of the 52,505 patients in the register, 4315 (8%) were identified as being in secondary prevention. Overall, 53% were noted as receiving an antiplatelet agent while 4% were taking warfarin therapy. Only 64% (2780) had a complete lipid profile on record while 38% were being treated with a hypolipidemic agent. In the treated group, only 30% had a low density lipoprotein cholesterol level below 3.0 mmol/L compared with 22% in the untreated group. CONCLUSIONS: A large number of patients identified as being in secondary prevention were not screened for dyslipidemias, and, of those who were, the majority were undertreated according to current recommendations. Antiplatelet agents were more widely prescribed but potentially underused.

Aged↗
PubMed1998

The lipophosphoglycan of Leishmania donovani up-regulates HIV-1 transcription in T cells through the nuclear factor-kappaB elements.

We have recently demonstrated that the parasite Leishmania donovani and its surface molecule, lipophosphoglycan (LPG), can activate HIV-1 replication in monocytoid cells. Our present interest was to determine whether LPG could also up-regulate HIV-1 transcription in T cells. Using a CD4-positive human lymphoid T cell line (1G5) containing a stably integrated HIV-1 long terminal repeat (LTR)-luciferase construct, we found that LPG is a potent inducer of HIV-1 LTR activity. Treatment of 1G5 cells with signaling antagonists revealed that protein tyrosine kinase- and protein kinase A-dependent pathways were actively participating in the LPG-induced enhancement of HIV-1 LTR-driven activity. Transfection of Jurkat E6.1 cells with plasmids containing wild-type and nuclear factor-kappaB (NF-kappaB)-mutated HIV-1 LTR-luciferase constructs has suggested a role for NF-kappaB binding sites in the LPG-mediated induction of HIV-1 LTR activity. An LPG-induced binding factor specific to the NF-kappaB consensus sequences could be observed using electrophoretic mobility shift assay. Finally, transfection experiments performed with a vector containing HIV-1 kappaB binding sites only showed similar LPG-mediated induction, which was abrogated by sodium salicylate, a known NF-kappaB inhibitor. We thus demonstrate that the LPG-mediated induction of HIV-1 LTR activity in T cells involves several second messengers culminating in activation of HIV-1 LTR-driven transcription via NF-kappaB-binding consensus sequences. In conclusion, these results reinforce the idea that L. donovani is a putative cofactor in HIV-1 pathogenesis.

Animals↗
PubMed1998

Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells.

Tuberculosis has emerged as an epidemic, extended by the large number of individuals infected with human immunodeficiency virus type 1 (HIV-1). The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis (M. tuberculosis) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system. These experiments are of prime importance considering that CD4-expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals. Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR, it was first found that culture protein filtrates (CFP) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM. The implication of protein tyrosine kinase(s), protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7. It was also determined, using electrophoresis mobility shift assays, that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB. M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type, but not the kappaB-mutated, HIV-1 LTR region. Finally, the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha. The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection.

Binding Sites↗
PubMed1998

Cardiovascular disease. Physician attitudes toward prevention and treatment.

OBJECTIVE: Survey of physician attitudes toward practising cardiovascular disease prevention. DESIGN: Questionnaire administered via telecommunication from 1992 through 1994. SETTING: The FAMUS (Family Medicine, University of Sherbrooke) project, between 1992 and 1996, used weekly telecommunication to collect data from 200 general practitioners throughout the province of Quebec on cardiovascular disease risk factors and their treatment. PARTICIPANTS: Of 200 physicians contributing to the FAMUS project, 156 completed questionnaires (response rate 78%). MAIN OUTCOME MEASURES: Variations in attitudes to prevention policy and risk factor interventions. RESULTS: Survey results revealed physicians knew important risk factors for cardiovascular disease but differed in attitudes toward efficacy of treatment. Intervention to control cholesterol was thought to be very effective by 21.2% (95% confidence interval [CI] 21.2 +/- 6.4) and without effect by 10.3% (95% CI 10.3 +/- 4.8). Intervention to improve dietary habits was considered ineffective by 48.1% (95% CI 48.1 +/- 7.8). Confidence in managing risk factors varied; most respondents described themselves as only moderately skilled. A few practitioners (30.1%; 95% CI 30.1 +/- 7.2) acknowledged practice guidelines as an important source of information on which to base preventive interventions. Only 14.7% (95% CI 14.7 +/- 5.6) of those surveyed included remuneration as contributing to their implementation of prevention activities in practice. CONCLUSIONS: Variations in physician attitudes could influence risk factor intervention. Interventions to change lifestyle are associated with uncertainty about patient compliance, efficacy of treatment, and ability to effect lifestyle changes.

Adult↗
PubMed1997

Activation of HIV-1 long terminal repeat transcription and virus replication via NF-kappaB-dependent and -independent pathways by potent phosphotyrosine phosphatase inhibitors, the peroxovanadium compounds.

Replication of human immunodeficiency virus type 1 (HIV-1) is increased by different cytokines and T cell activators, also known to modulate tyrosine phosphorylation levels. A novel class of protein tyrosine phosphatase (PTP) inhibitors, peroxovanadium (pV) compounds, were tested for a putative effect on HIV-1 long terminal repeat (LTR) activity. We found that these PTP inhibitors markedly enhanced HIV-1 LTR activity in 1G5 cells, a stably transfected cell line that harbors an HIV-1 LTR-driven luciferase construct. A direct correlation between the extent of tyrosine phosphorylation and the level of HIV-1 LTR inducibility was seen after treatment with three different pV compounds. Transient transfection experiments were carried out in several T cell lines, and after addition of pV, a marked increase in HIV-1 LTR activity was measured. Monocytoid cells were tested using U937-derived cell lines and were also found to be sensitive to the pV-mediated potentiating effect on HIV-1 LTR activity. A significant reduction of the pV-mediated increase in HIV-1 LTR activity was seen in cells transiently transfected with an HIV-1 LTR-driven luciferase construct bearing a mutation in both NF-kappaB binding sites although detectable levels of induction remained. Electrophoretic mobility shift assays allowed the identification of the nuclear translocation of the NF-kappaB p50.p65 heterodimer complex induced by pV compounds. A dominant negative version of the repressor IkappaBalpha mutated on serines 32 and 36 impeded pV-induced NF-kappaB-dependent luciferase activity. Western blot analysis showed a clear diminution in the protein level of IkappaBalpha starting 30 min after pV treatment of Jurkat E6.1 cells which is indicative of its degradation. On the other hand, no increase in tyrosine phosphorylation was observed on IkappaBalpha itself. Finally, we tested the PTP inhibitors on four cell lines latently infected with HIV-1 and showed a consistent pV-mediated increase in virion production. Thus, our studies suggest that pV-mediated activation of HIV-1 LTR activity is controlled by the nuclear translocation of the NF-kappaB transcription factor, which is mediated by IkappaBalpha serine phosphorylation and degradation, but also by a still undefined NF-kappaB-independent pathway.

Cell Line↗
PubMed1997

Impact of measurement and feedback on vaccination coverage in public clinics, 1988-1994.

OBJECTIVE: To investigate whether a reported rise in vaccination coverage in Georgia public clinics during the period 1988 through 1994 was artifactual or real and, if real, to determine the extent to which the rise could be associated with a program of measurement and feedback. DESIGN: Examination of data from Georgia public clinics, doses-administered records, and National Health Interview Surveys. SETTING/PARTICIPANTS: Children attending Georgia public clinics. INTERVENTION: Measurement of vaccination coverage and feedback to providers. MAIN OUTCOME MEASURE: Vaccination coverage rates. RESULTS: For the period 1988 through 1994, 136 004 Georgia public clinic vaccination records for children 21 to 23 months of age were reviewed. Median series-completion rates at public clinics rose from 53% to 89%, while indexes of under-vaccination fell: missed opportunities for simultaneous vaccination (6% to 0%), lost contact for more than 12 months (14% to 1%), and first vaccination more than 1 month late (19% to 8%). According to the independent doses-administered database, the proportion of children starting the primary series very late (> or =12 months old) fell from 14% to 6%, and the series-completion index rose from 64% to 83%, suggesting that improvements could not be wholly ascribed to better clinic record keeping. In 1988, vaccination coverage of children 24 months of age in the National Health Interview Survey (NHIS) was 53%, identical to median public clinic coverage in Georgia; in 1993, NHIS coverage was 60%, while median public clinic coverage in Georgia was 90%, suggesting that the rise in coverage in Georgia public clinics exceeded national trends. Patterns within the coverage changes suggest an association with the process of measurement and feedback. CONCLUSIONS: A marked increase in vaccination coverage occurred in Georgia public clinics associated with a program of annual measurement and feedback.

Community Health Centers↗
PubMed1997

Drug sensitivity of human immunodeficiency virus type 1 isolates after ribavirin therapy.

The antiviral agent ribavirin is effective against several virally induced diseases, and there is evidence that it might prove useful against human immunodeficiency virus type 1 (HIV-1) infection. Thus, there is interest in studying the resistance level of HIV-1 isolates to ribavirin following drug therapy. Low-passage clinical strains of HIV-1 were isolated from 3 patients undergoing treatment with ribavirin for 5-9 months. No significant changes in drug sensitivity were seen for sequential virus samples obtained before, during, and after antiviral therapy. These observations suggest that the appearance of a resistant phenotype is not induced by treatment with ribavirin in HIV-1-infected persons.

Adult↗
PubMed1995

Homologous interference resulting from the presence of defective particles of human immunodeficiency virus type 1.

Defective particles are naturally occurring virus mutants that lack one or more genes required for viral replication. Such viruses may affect positively or negatively the symptoms of the disease. Thus, it is of great interest to measure the role played by defective particles in the process of human immunodeficiency virus (HIV) infection since accumulating evidence indicates that a great proportion of HIV genomes are defective. We used defective particles produced by two stable cellular clones (UHC-8 and UHC-18) to investigate whether they can affect replication of infectious viral particles generated by a human T-cell line transfected with a molecular HIV-1 clone. Progeny virus harvested from UHC-8 cells has no reverse transcriptase and integrase proteins, while UHC-18 has no reverse transcriptase protein. We demonstrate here that coinoculation of a T-lymphoid cell line and of peripheral blood mononuclear cells with defective and infectious particles leads to a dramatic inhibition of virus replication. Defective particles do not interfere with virus production from proviral DNA. Rather, the inhibition of reinfection events seems to be their mechanism of action. This model closely parallels the in vivo conditions and demonstrates that defective particles may limit the spread of infection and progression of the disease by reducing the yield of infectious virus.

CD4 Antigens↗
PubMed1995

Activation of human immunodeficiency virus type 1 in monocytoid cells by the protozoan parasite Leishmania donovani.

In this study, we demonstrated that the protozoan parasite Leishmania donovani and one of its major surface molecules, the lipophosphoglycan (LPG), can induce human immunodeficiency virus type 1 (HIV-1) expression in U1 and OM-10.1, two cell lines of monocytoid origin latently infected with HIV-1. Treatment of U1 cells with various concentrations of LPG (1, 5, and 10 microM) resulted in a dose-dependent secretion of tumor necrosis factor alpha (TNF-alpha). Suppression of LPG-induced HIV-1 expression by polyclonal anti-TNF-alpha antibodies further confirmed the involvement of this cytokine. Results from these studies indicate that the protozoan parasite L. donovani can induce the secretion of TNF-alpha that will function in an autocrine or paracrine manner to upregulate HIV-1 expression. Our data suggest for the first time that this protozoan parasite can be viewed as a potential cofactor in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The TEAM evaluation approach to Project FAMUS, a pan-Canadian risk register for primary care.

The application of the TEAM--Total Evaluation and Acceptance Methodology--to the development of Project FAMUS--Family Medicine, University of Sherbrooke--is described. Project FAMUS is concerned with the establishment of a pan-Canadian risk register, the data being provided from a network of 800 family physicians distributed across Canada. Emphasis is on the first phase of the project and the overall evaluation strategy.

Computer User Training↗
PubMed1991

Brain growth and differentiation in two fetal bats: qualitative and quantitative aspects.

The development of the main brain components in two fetal bats (one insectivorous and one frugivorous type) is studied quantitatively and comparatively. The telencephalon, cerebellum, and diencephalon grow faster in the frugivorous bat. The brainstem maintains a greater relative volume throughout in the insectivorous type. The morphology and density of neurons in the cerebellum, caudate nucleus, olfactory mitral stratum, and neocortical layer II suggest that there exists an initial delay in development in the frugivorous bat; through subsequent reordering, however, it becomes more advanced in development, in accordance with the more progressive status of the adult forms in its category. In this there may be a certain ontogenetic recapitulation of a possible chiropteran phylogeny. These comparisons also point to the precociousness of the functional determination of those structures that are related to future behavior in a purely deterministic, non-teleological sense. The qualitative differentiation appears to be more significant than might be expected in comparison with the quantitative proliferation. Technical problems involved in the study of brain morphogenesis are discussed, especially the difficulty of distinguishing the respective effects of cell multiplication, cell death, and artificial increase in cell density through tissue shrinkage.

Animals↗
PubMed1990

The humoral immune response to type 1 oral poliovirus vaccine in children previously immunized with enhanced potency inactivated poliovirus vaccine or live oral poliovirus vaccine.

Sixty-one children who had previously received three doses of enhanced potency inactivated poliovirus vaccine (epIPV) at 2, 4, and 18 months of age and 56 children who had previously received oral poliovirus vaccine (OPV) according to the same schedule were challenged with a single dose of monovalent, type 1 oral poliovirus vaccine (OPV1) between 19 and 52 months of age. Before the OPV1 challenge, the previously epIPV-immunized recipients had a geometric mean poliovirus type 1 microneutralization antibody titer (geometric mean titer [GMT]) of 11.1 IU, which was significantly higher than the prechallenge GMT of 2.2 IU among the children who had previously received OPV. Three weeks after the OPV1 challenge, the GMTs for the epIPV-immunized recipients and the OPV-immunized recipients were 35.3 IU and 5.1 IU, respectively. For the epIPV-immunized recipients, both the prechallenge GMT and the postchallenge GMT were dependent on the D antigen content of the vaccine that they had previously received. A fourfold or greater rise in poliovirus type 1 antibody occurred after the OPV1 challenge in 50.9% of the epIPV-immunized children and in 28.6% of the OPV-immunized children; this difference was statistically significant. For both groups, antibody boosts were inversely correlated with the pre-challenge serum antibody titer. However, the epIPV-immunized children consistently were more likely to boost than the OPV-immunized children at equivalent levels of prechallenge antibody. This experience indicated that OPV1 administration effectively raises the level of serum antibody in children previously immunized with three doses of epIPV, especially in children with lower levels of preexisting antibody. This booster response was superior to the booster response of children who received three doses of OPV.

Antibodies, Viral↗
PubMed1988

Serologic response to oral polio vaccine and enhanced-potency inactivated polio vaccines.

In a randomized, controlled trial carried out from November 1980 to July 1983 involving 1,114 infants in Baltimore City and in Baltimore and Prince George's counties, Maryland, the serologic response to three doses of two enhanced-potency inactivated polio vaccines was compared with the response to three doses of oral polio vaccine. The mean ages at vaccination were 2.2, 4.7, and 19.9 months, respectively, for the three doses. Seroconversion after the first dose varied from 35% to 84%, and it was higher after oral polio vaccine than after either of the enhanced-potency inactivated polio vaccines for polioviruses types 2 and 3. Approximately two and one-half and 16 months after the second dose, almost all inactivated polio vaccine recipients had antibodies against all three virus types (98-100%). Fewer oral polio vaccine recipients had detectable antibodies to type 1 (89-92%) and to type 3 (96%). After three doses of vaccine, all children had antibodies against types 2 and 3. Approximately 1% of the inactivated polio vaccine recipients and 3% of the oral polio vaccine recipients lacked antibody to type 1. One or two doses of oral polio vaccine stimulated higher reciprocal geometric mean antibody titers against type 2 poliovirus than did the inactivated polio vaccine. For the other two types, the results were mixed. The third dose of inactivated polio vaccine produced significant increases in the reciprocal geometric mean titers against each of the three poliovirus types and resulted in significantly higher reciprocal geometric mean titers after three doses of vaccine for recipients of inactivated polio vaccine than for recipients of oral polio vaccine.

Antibodies, Viral↗