Molecular epidemiology of hepatitis C virus infection amongst intravenous drug users in rural communities

The prevalence of hepatitis C virus (HCV) infection amongst a group of intravenous drug users (IVDUs) resident in West Suffolk (East Anglia, England) was investigated and compared with the prevalence of infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV). In addition, both the level of HCV persistence, as defined by detection of viral RNA, and the HCV genotypes present in this population were determined. It was found that HCV antibodies were present in 59% of those tested; by comparison 22% had antibodies to HBV and 1% antibodies to HIV. HCV RNA was found in 44% of those with HCV antibody. HCV genotype 1 was the most prevalent within this population although both genotypes 2 and 3 were also represented. © 1995 Wiley-Liss, Inc.     

Acute hepatitis B virus infection by genotype F despite successful vaccination in an immune-competent German patient.

BACKGROUND: Hepatitis B Virus (HBV) infection is a leading cause of chronic hepatitis and liver cirrhosis worldwide, and efficient protection can usually be achieved by vaccination that is based on recombinant HBsAg protein from HBV genotype A and D. RESULTS: Here we report the case of a fully immune-competent German patient that acquired a symptomatic acute HBV infection during adulthood despite a complete and formally successful vaccination, which had resulted in anti-HBs titers considered protective. Further phylogentic analysis identified an infection with the rare genotype F of HBV, possibly acquired in Spain, without apparent aberrations in the immunodominant 'a' determinant domain of the envelope gene. However, sequence comparisons revealed that all reported genotype F isolates display marked differences from the other genotypes in this domain which serves as an epitope for humoral immune responses. CONCLUSIONS: The rare HBV genotype F, as detected in this immune-competent, previously vaccinated patient, has marked sequences differences in the envelope/polymerase gene. Therefore, current HBV vaccines based on genotype A and D may not result in full protective immunity towards viral strains from genotype F.     

Changing contexts? The effects of a primary prevention program on classroom levels of peer relational and physical victimization

Whereas school‐based prevention programs often target deficits in individual children's social skills in order to limit their aggression or exposure to peer victimization, there is increasing evidence that school‐wide and classroom‐level factors can also affect the success of these programs. This short‐term longitudinal study involved 432 elementary school students from 44 classrooms in 17 urban schools. We investigated whether classroom characteristics (average levels of social competence, emotional problems, and behavioral problems) and school‐wide characteristics (proportion of children on income assistance and implementation of a peer victimization prevention program—the Walk away, Ignore, Talk, and Seek help [W.I.T.S.] program) experienced in Grade 1 influences changes in children's reports of relational and physical victimization at the end of Grade 2. Findings showed that classroom levels of emotional problems predicted increases in relational victimization (beyond individual differences in emotional and behavioral problems). Classroom levels of behavioral problems predicted reports of increases in physical victimization (beyond individual differences). Classroom levels of social competence also interacted with individual levels of emotional problems such that children with higher levels of emotional problems in classes with more socially competent children reported more relational and physical victimization. Higher school levels of poverty and lack of program involvement also predicted higher levels of physical victimization, beyond individual and classroom effects. The capacity of the W.I.T.S. program to influence classroom level characteristics and the moderating effects of school poverty on victimization were also assessed. © 2003 Wiley Periodicals, Inc. J Comm Psychol 31: 397–418, 2003.     

PCR based mutation screening of the laminin alpha2 chain gene (LAMA2): application to prenatal diagnosis and search for founder effects in congenital muscular dystrophy.

Classical congenital muscular dystrophy with merosin deficiency is caused by mutations in the laminin alpha2 chain gene (LAMA2). Extended sequencing of the introns flanking the 64 LAMA2 exons was carried out and, based on these sequences, oligonucleotide primers were designed to amplify the coding region of each exon separately. By PCR-SSCP analysis, we identified eight new mutations in nine families originating from various countries. All induced a premature truncation of the protein, either in the short arm or in the globular C-terminal domain. A 2 bp deletion in exon 13, 2098delAG, was found in three French non-consanguineous families and a nonsense mutation of exon 20, Cys967stop, in two other non-consanguineous families originating from Italy. Determination of rare intragenic polymorphisms permitted us to show evidence of founder effects for these two mutations suggesting a remote degree of consanguinity between the families. Other, more frequent polymorphisms, G to A 1905 (exon 12), A to G 2848 (exon 19), A to G 5551 (exon 37), and G to A 6286 (exon 42), were used as intragenic markers for prenatal diagnosis. This study provides valuable methods for determining the molecular defects in LAMA2 causing merosin deficient congenital muscular dystrophy.     

Influence of outdoor aeroallergens on hospitalization for asthma in Canada

BACKGROUND: The risk of hospitalization for asthma caused by outdoor aeroallergens is largely unknown. OBJECTIVE: The objective of this study was to determine the association between changes in outdoor aeroallergens and hospitalizations for asthma from the Pacific coast to the Atlantic coast of Canada. METHODS: A daily time series analysis was done to test the association between daily changes in aeroallergens and daily changes in hospitalizations for asthma during a 7-year period between 1993 and 2000 in 10 of the largest cities in Canada. Results were adjusted for long-term trends, day of the week, climate, and air pollution. RESULTS: A daily increase, equivalent to the mean value of each allergen, was associated with the following percentage increase in asthma hospitalizations: 3.3% (95% CI, 2.3 to 4.1) for basidiomycetes, 3.1% (95% CI, 2.8 to 5.7) for ascomycetes, 3.2% (95% CI, 1.6 to 4.8) for deuteromycetes, 3.0% (95% CI, 1.1 to 4.9) for weeds, 2.9% (95% CI, 0.9 to 5.0) for trees, and 2.0% (95% CI, 1.1 to 2.8) for grasses. After accounting for the independent effects of trees and ozone, the combination of the 2 was associated with an additional 0.22% increase in admissions averaged across cities (P <.05). CONCLUSION: These findings provide evidence for the hypothesis that aeroallergens are an important cause of severe asthma morbidity across Canada, and in some situations there might be a modest synergistic adverse effect of ozone and aeroallergens combined.     

Routine mortality monitoring for detecting mass murder in UK general practice: test of effectiveness using modelling.

BACKGROUND: The Shipman Inquiry recommended mortality rate monitoring if it could be 'shown to be workable' in detecting a future mass murderer in general practice. AIM: To examine the effectiveness of cumulative sum (CUSUM) charts, cross-sectional Shewhart charts, and exponentially-weighted, moving-average control charts in mortality monitoring at practice level. DESIGN OF STUDY: Analysis of Scottish routine general practice data combined with estimation of control chart effectiveness in detecting a 'murderer' in a simulated dataset. METHOD: Practice stability was calculated from routine data to determine feasible lengths of monitoring. A simulated dataset of 405,000 'patients' was created, registered with 75 'practices' whose underlying mortality rates varied with the same distribution as case-mix-adjusted mortality in all Scottish practices. The sensitivity of each chart to detect five and 10 excess deaths was examined in repeated simulations. The sensitivity of control charts to excess deaths in simulated data, and the number of alarm signals when control charts were applied to routine data were estimated. RESULTS: Practice instability limited the length of monitoring and modelling was consequently restricted to a 3-year period. Monitoring mortality over 3 years, CUSUM charts were most sensitive but only reliably achieved >50% successful detection for 10 excess deaths per year and generated multiple false alarms (>15%). CONCLUSION: At best, mortality monitoring can act as a backstop to detect a particularly prolific serial killer when other means of detection have failed. Policy should focus on changes likely to improve detection of individual murders, such as reform of death certification and the coroner system.     

Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa

Interleukin-18 (IL-18) is a potent cytokine with many different proinflammatory activities. To study the role of IL-18 in the pathogenesis of Pseudomonas pneumonia, IL-18-deficient (IL-18(-/-)) and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. IL-18 deficiency was associated with reduced outgrowth of Pseudomonas in the lungs and diminished dissemination of the infection. In addition, pulmonary inflammation (histopathology) and levels of tumor necrosis factor alpha, IL-6, and macrophage inflammatory protein-2 in lungs and plasma were lower in IL-18(-/-) mice. Consistent with results obtained for IL-18(-/-) mice, treatment of wild-type mice with a neutralizing IL-18 binding protein-immunoglobulin G Fc fusion construct also attenuated outgrowth of Pseudomonas compared with that for mice treated with a control protein. These results demonstrate that the presence of endogenous IL-18 activity facilitates inflammatory responses in the lung during Pseudomonas pneumonia, concurrently impairing bacterial clearance.