Clinical and Epidemiological Relevance of Quantitating Hepatitis E Virus-Specific Immunoglobulin M

Diagnosis of acute hepatitis E by detection of hepatitis E virus (HEV)-specific immunoglobulin M (IgM) is an established procedure. We investigated whether quantitation of HEV IgM and its ratio to HEV total Ig furnished more information than conventional IgM tests that are interpreted as positive or negative. A previously described indirect immunoassay for total Ig against a baculovirus-expressed HEV capsid protein was modified to quantitate HEV-specific IgM in Walter Reed (WR) antibody units by using a reference antiserum and the four-parameter logistic model. A receiver-operating characteristics curve derived from 197 true-positive specimens and 449 true-negative specimens identified 30 WR units/ml as an optimum cut point. The median HEV IgM level in 36 patients with acute hepatitis E fell from 3,000 to 100 WR units/ml over 6 months, suggesting that 100 WR units/ml would be a more appropriate cut point for distinguishing recent from remote IgM responses. Among three hepatitis E case series, determination of the HEV IgM-to-total-Ig ratio in acute-phase serum revealed that most patients had high ratios consistent with primary infections whereas a few had low ratios, suggesting that they had sustained reinfections that elicited anamnestic antibody responses. The diagnostic utility of the new IgM test was similar to that of a commercially available test that uses different HEV antigens. In conclusion, we found that HEV IgM can be detected specifically in >95% of acute hepatitis E cases defined by detection of the virus genome in serum and that quantitation of HEV IgM and its ratio to total Ig provides insight into infection timing and prior immunity.     

Genome-wide examination of myoblast cell cycle withdrawal during differentiation.

Skeletal and cardiac myocytes cease division within weeks of birth. Although skeletal muscle retains limited capacity for regeneration through recruitment of satellite cells, resident populations of adult myocardial stem cells have not been identified. Because cell cycle withdrawal accompanies myocyte differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line previously used to characterize myocyte differentiation, also would provide a model for studying cell cycle withdrawal during differentiation. C2C12 cells were differentiated in culture medium containing horse serum and harvested at various time points to characterize the expression profiles of known cell cycle and myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased dramatically in confluent cultures 48 hr after addition of horse serum, as cells started to form myotubes. This finding was preceded by up-regulation of MyoD, followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in proliferating cultures and became undetectable in cultures containing 40% fused myotubes, as levels of p21(WAF1/Cip1) increased and alpha-actin became detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte differentiation following a course that recapitulates this process in vivo, we performed a genome-wide screen to identify other gene products involved in this process. Using microarrays containing approximately 10,000 minimally redundant mouse sequences that map to the UniGene database of the National Center for Biotechnology Information, we compared gene expression profiles between proliferating, differentiating, and differentiated C2C12 cells and verified candidate genes demonstrating differential expression by RT-PCR. Cluster analysis of differentially expressed genes revealed groups of gene products involved in cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we identified several genes, including DDAH2 and Ly-6A, whose expression specifically was up-regulated during cell cycle withdrawal coincident with early myoblast differentiation.     

A pilot study of dental caries status in relation to knowledge, attitudes and practices in oral health in Myanmar

This study was to determine the dental caries prevalence among the Myanmar population, and to investigate the correlations between oral clinical indices and knowledge, attitudes and practices (KAP) on oral health. Subjects were randomly selected from 140,000 people residing in the Kyauktan township in a cross-sectional community-based study. The present analysis was confined to 739 subjects (353 males and 386 females) aged 12, 35-44 and 65-74 years, who were divided into two specified groups based on urban or rural location. KAP on oral health data and social demographic information were collected, while dental caries status was assessed by DMFT. The mean number of decayed teeth (DT) in rural areas was higher than that in urban areas, while the mean number of filled teeth (FT) in rural areas was lower than that in urban areas. Mean knowledge and attitude scores for correct answers were also significantly higher for the urban than the rural subjects. There were statistically significant correlations between the correct/incorrect responses to knowledge and attitude questionnaires on oral health and the mean number of DMFT. KAP pertaining to oral health of Myanmar population, especially those of rural subjects, might not be satisfactory and related to threaten their dental caries status.     

Haemostatic disturbances in patients bitten by Russell''s viper (Vipera russelli siamensis) in Burma

Patients who are severely envenomed by Russell's viper develop DIC which is frequently associated with spontaneous bleeding and incoagulable blood. These haemostatic disturbances may be responsible for death or organ/tissue damage both through haemorrhage and microvascular occlusion by fibrin thrombi. The most striking laboratory features of the coagulopathy developing after Russell's viper bite in the 42 patients studied were depletion of fibrinogen (mean 0.09 g/l, range 0-0.6), factor V (6.5 u/dl, range 0-17), factor X (35 u/dl, range 1-85), factor XIIIa (57 u/dl, range 15-82), plasminogen (61 u/dl, range 10-92), antiplasmin (36 u/dl, range 14-62). Protein C (49 u/dl, range 15-100) and platelets (104 x 10(9)/l, range 25-197). Intense fibrinolytic activity was detected in all cases with marked elevation of FDPs (1614 micrograms/ml, range 350-3000), a large proportion of which were cross-linked (1058 micrograms/ml, range 38-3000). The monospecific Burmese antivenom appeared to be very effective in neutralizing the venom procoagulants and in restoring blood coagulability. Moreover, the unexpectedly normal level of AT III provides a theoretical basis for the use of heparin to enhance the inactivation of those serine proteases present before antivenom administration.     

Prognostic Tools for Early Mortality in Hemorrhagic Stroke: Systematic Review and Meta-Analysis

Background and Purpose

Several risk scores have been developed to predict mortality in intracerebral hemorrhage (ICH). We aimed to systematically determine the performance of published prognostic tools.

Methods

We searched MEDLINE and EMBASE for prognostic models (published between 2004 and April 2014) used in predicting early mortality (<6 months) after ICH. We evaluated the discrimination performance of the tools through a random-effects meta-analysis of the area under the receiver operating characteristic curve (AUC) or c-statistic. We evaluated the following components of the study validity: study design, collection of prognostic variables, treatment pathways, and missing data.

Results

We identified 11 articles (involving 41,555 patients) reporting on the accuracy of 12 different tools for predicting mortality in ICH. Most studies were either retrospective or post-hoc analyses of prospectively collected data; all but one produced validation data. The Hemphill-ICH score had the largest number of validation cohorts (9 studies involving 3,819 patients) within our systematic review and showed good performance in 4 countries, with a pooled AUC of 0.80 [95% confidence interval (CI)=0.77-0.85]. We identified several modified versions of the Hemphill-ICH score, with the ICH-Grading Scale (GS) score appearing to be the most promising variant, with a pooled AUC across four studies of 0.87 (95% CI=0.84-0.90). Subgroup testing found statistically significant differences between the AUCs obtained in studies involving Hemphill-ICH and ICH-GS scores (p=0.01).

Conclusions

Our meta-analysis evaluated the performance of 12 ICH prognostic tools and found greater supporting evidence for 2 models (Hemphill-ICH and ICH-GS), with generally good performance overall.     

The association between hepatitis C virus and HIV-1 in preparatory cohorts for HIV vaccine trials in Thailand

OBJECTIVES: To study the association between hepatitis C virus (HCV) and HIV-1, and HCV seropositivity as an indicator of HIV-1 risk behavior for HIV vaccine preparatory cohorts in Thailand. DESIGN: Cross-sectional study of HIV-1-infected persons identified at screening for potential HIV vaccine trial cohort studies. METHODS: Sera from HIV-1-infected and uninfected volunteers was matched by age, sex, and community, and tested for HCV reactivity. Logistic regression methods were used to measure associations between HIV-1, HCV and other risk factors for HIV infection. RESULTS: The prevalence of HCV among HIV-negative controls was 8.3% (6/72) for men and 4.2% (5/118) for women. Co-infection with HIV and occurred in 50.7% (37/73) of men and 3.4% (4/118) of women. Among men who reported injection drug use (IDU), 96.4% (27/28) were HCV seropositive. No women reported IDU. HCV was associated with HIV infection [odds ratio (OR), 11.3; 95% confidence interval (CI), 4.4-29.3] and IDU (OR, 12.0; 95% CI, 3.4-41.9) among men, but not women (OR, 0.8; 95% CI, 0.2-3.0). After adjustment for potential confounding, HCV, but not IDU, remained strongly associated with HIV-1 infection among men (OR, 9.4; 95% CI, 2.7-32.6). CONCLUSIONS: The strong associations between HCV seropositivity, HIV-1 infection, and IDU history suggest that IDU was reported accurately in this study. The surprisingly high prevalence of HCV among HIV-1-infected young men may assist health policy makers in the choice of behavioral interventions for this important subgroup of the population.     

The association between polypharmacy and late life deficits in cognitive,physical and emotional capability: a cohort study

International Journal of Clinical Pharmacy - Background Polypharmacy is a growing health concern for older adults and is associated with poorer clinical outcome. Objective This study aim is to...